program director/principal investigator (last, first, middle)...

Program Director/Principal Investigator (Last, First, Middle):

PHS 398/2590 (Rev. 06/09) Page Biographical Sketch Format Page

BIOGRAPHICAL SKETCH Provide the following information for the Senior/key personnel and other significant contributors in the order listed on Form Page 2. Follow this format for each person. DO NOT EXCEED FOUR PAGES.

NAME Emine Ercikan Abali eRA COMMONS USER NAME (credential, e.g., agency login) ABALIEM

POSITION TITLE Associate Professor of Biochemistry, Pharmacology and Medicine

EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable.) INSTITUTION AND LOCATION DEGREE

(if applicable) MM/YY FIELD OF STUDY

University of Southwestern Louisiana, Lafayette, LA University of Southwestern Louisiana, Lafayette, LA The Ohio State University, Columbus, OH Cornell University Graduate School of Medical Sciences and Memorial Sloan Kettering Cancer Center, New York, NY Memorial Sloan Kettering Cancer Center, NY, NY Columbia University, NY, NY

B.Sc. M.S. Ph.D. student Ph.D. Postdoc Postdoc

1982-1986 1988-1988 1989-1990 1990-1996 1996-1998 1998-1999 (10months)

Chemistry Chemistry Chemistry Pharmacology Molecular Therapeutics Biological Sciences

A. Personal Background The overall aim of this project is to use dihydrofolate reductase (DHFR) as a prototype for other NAD(P) binding dehydrogenases to identify novel NAD(P) analogues that specifically target the NADPH binding site of DHFR as potent inhibitors of cancer cells. Specifically, we plan to investigate metabolism of NADPS in cell lines and in xenograft animal and to perform in silico screening of the NADPH binding site to identify potential new inhibitors targeted to DHFR. Lastly, we will determine further characterize the mechanism of action of NADPS in accelerating the degradation of DHFR in order to address development of drug-resistance to this new class of inhibitors. I have the expertise, leadership and enthusiasm to be in charge of determining the metabolism of NADPS and studying the mechanism of degradation of NADPS. My research area over the years focused on antifolate metabolism specifically to MTX, inhibitor of dihydrofolate reductase. I have successfully lead Dr. Bertino’s project as a Co-PI in his previous R01 grants and trained many undergraduate, graduate students and postdoctoral fellows. Dr. Bertino (PI), Banerjee (Investigator) and I (Co-PI) have worked together over many projects and our publication record is a testimony for our successful collaborations. Our on-going research builds logically to the hypotheses to be tested in the proposed project. B. Positions and Honors Positions and Employment Visiting Assistant Professor, Department of Molecular Biology and Genetics 1999-2001 Bilkent University, Turkey Assistant Professor, Department of Medicine and Pharmacology 2002-2009 The Cancer Institute of New Jersey, RWJMS-UMDNJl Associate Professor of Biochemistry, RWJMS-UMDNJ 2009-present Other Experience and Professional Memberships Member, American Medical Biochemistry Course Directors Member, Scientific Review Board of CINJ, RWJMS, UMDNJ Member, Cancer Institute of New Jersey Member, Graduate School of Biomedical Sciences, UMDNJ-RUTGERS Associate member of the Cellular and Molecular Pharmacology Graduate Program, UMDNJ


PHS 398/2590 (Rev. 06/09) Page Continuation Format Page

Member of American Association for Cancer Research Member of AACR-Women in Cancer Research Member of RNA society Member of American Society of Biochemistry and Molecular Biology Honors Department of Medicine Grant Award 2005 Cancer Institute of New Jersey New Investigator Award 2002 Faculty Development Award, Bilkent University, Turkey 2000 American Association for Cancer Research-Bristol-Mayers-Young Investigator Award 1998 American Association for Cancer Research-Young Investigator from Pharmingen 1997 American Association for Cancer Research Travel Award from Roche 1996 Fulbright scholarship 1982-1986 Alpha Delta Kappa-International Teaching Scholarship 1982-1985 C. Selected Peer-reviewed Publications Most relevant to the current application

1. Ercikan, E.A., Waltham, M., Dicker, A.P., Schweitzer, B., Bertino, J.R. (1993) Effect of codon 22 mutations on substrate and inhibitor binding for human dihydrofolate reductase. Adv Exp Med Biol. 338, 515-519.

2. Ercikan, E.A., Banerjee, D., Waltham, M., Schneiders, B., Scotto, K., Bertino, J.R. (1993) Translational regulation of the synthesis of dihydrofolate reductase. Adv Exp Med Biol. 338, 537-540.

3. Rosowsky, A., Mota, C.E., Queener, S.F., Waltham, M., Ercikan, E.A., Bertino, J.R. (1995) 2,4-Diamino-5-substituted-quinazolines as inhibitors of a human dihydrofolate reductase with a site-directed mutation at position 22 and of the dihydrofolate reductases from Pneumocystis carinii and Toxoplasma gondii. J Med Chem. 38, 745-52.

4. Banerjee, D., Ercikan Abali, E.A., Waltham, M., Schneiders, B., Hochhauser, D., Li, W.W., Fan, J., Gorlick, R., Goker, E., Bertino, J.R. (1995) Molecular mechanisms of resistance to antifolates, a review. Acta Biochim Pol. 42, 457-464.

5. Ercikan Abali, E.A., Waltham, M., Dicker, A.P., Gritsman, H., Banerjee, D., Bertino, J.R. (1996) Variants of human dihydrofolate reductase with substitutions at leucine-22: effect on catalytic and inhibitor binding properties. Mol Pharmacol. 49, 430-437.

6. Hochhauser, D., Schneiders, B., Ercikan Abali, E.A., Gorlick, R., Muise-Helmericks, R., Li, W.W., Fan, J., Banerjee, D., Bertino, J.R. (1996) Effect of cyclin D1 overexpression on drug sensitivity in a human fibrosarcoma cell line. J Natl Cancer Inst. 88, 1269-1275.

7. Ercikan Abali, E.A., Mineishi, S., Nakahara, S., Tong, Y., Waltham, M.C., Chen, W., Banerjee, D., Bertino, J.R. (1996) Active site-directed double mutants of dihydrofolate reductase. Cancer Res. 56, 4142-4145.

8. Longo, G.S., Gorlick, R., Tong, W.P., Ercikan E, Bertino, J.R. (1997) Disparate affinities of antifolates for folylpolyglutamate synthetase from human leukemia cells. Blood 90, 1241-1245.

9. Ercikan Abali, E.A., Banerjee, D., Waltham, M.C., Scotto, K., Bertino, J.R. (1997) Dihydrofolate reductase protein inhibits its own translation by binding to dihydrofolate reductase mRNA sequences within the coding region. Biochemistry 36, 12317-12322.

10. Tong, Y., Liu-Chen, X., Ercikan Abali, E.A., Zhao, S.C., Banerjee, D., Bertino, J.R. (1998) Isolation and characterization of thymitaq (AG337) and 5-fluoro-2-deoxyuridylate-resistant mutants of human thymidylate synthase from ethyl methanesulfonate-exposed human sarcoma HT1080 cells. J Biol Chem. 273, 11611-11618.

11. Tong, Y., Liu-Chen, X., Ercikan Abali, E.A., Zhao, S.C., Banerjee, D., Maley, F., Bertino, J.R. (1998) Probing the folate-binding site of human thymidylate synthase by site-directed mutagenesis. Generation of mutants that confer resistance to raltitrexed, Thymitaq, and BW1843U89. J Biol Chem. ;273, 31209-31214.

12. Banerjee D., Tong, Y., Liu-Chen, X., Capiaux, J.R., Ercikan Abali, E., Takebe, N., O'Connor, O.A., Bertino, J.R. (1999) Protection of bone marrow cells from toxicity of chemotherapeutic agents



targeted toward thymidylate synthase by transfer of mutant forms of human thymidylate synthase cDNA. Gene Therapy: Bertino J.R. (ed.) Prog Exp Tumor Res. Basel, Karger 36, 107-114.

13. Bertino, J.R., Zhao, S.C., Mineishi, S., Ercikan Abali E., Banerjee D. (1999) Use of variants of dihydrofolate reductase in gene transfer to produce resistance to methotrexate and trimetrexate. Gene Therapy: Bertino J.R. (ed.) Prog Exp Tumor Res. Basel, Karger 36, 82-94.

14. Ural, A.U., Takebe, D., Adhikari, D., Ercikan-Abali, E., Banerjee, D., Barakat, R, Bertino, J.R. (2000) Gene Therapy for Endometrial Carcinoma with the Herpes Simplex Thymidine Kinase Gene. Gynecol Oncol. 76(3), 305-310.

MANDATORY REPATRIATION TO MEET HER OBLIGATIONNS FOR FULBRIGHT SCHOLARSHIP FROM

1999-2001 15. Skacel N, Menon LG, Prasunkumar J. Misra, Peters R, Scotto, KW, Banerjee D, Bertino JR and

Ercikan-Abali,E. (2005) Identification of amino acids required for the functional upregulation of human dihydrofolate reductase protein in response to antifolate treatment. J Biol Chem. 280 (24), 22721- 22731.

16. Ercikan Abali E, Skacel N, Menon LG, Mishra PJ, Banerjee D and Bertino JR (2007) Mechanism of Upregulation of Dihydrofolate Reductase” In: Peters GJ, Jansen G, eds. Chemistry and Biology of Pteridines and Folates Heilbronn: SPS Verlagsgesellschaft, 105-118.4.

17. Yi-Ching Hsieh, Nancy Skacel, Nitu Bansal, Kathleen Scotto, Debabrata Banerjee,Joseph R. Bertino and Emine Ercikan Abali. Species Specific Differences in Translational Regulation of Dihydrofolate Reductase. Mol Pharmacol. 2009 76(4):723-33.2.

Invited Articles (Reviews, Editorials, etc.) In Journals; Chapters; Books; other Professional Communication

1. Ercikan Abali, E, Skacel, NE, Celikkaya, H, Hsieh YC. (2008) Regulation of Human Dihydrofolate Reductase Activity and Expression . Vitam. Horm. 79,267-292.

C. Research Support. On-going Research Support- None Completed Research Support. 15 R01 CA 08010-41 (Co-PI) 12/1/2004-11/30/2009 NCI Mechanism of action of folate antagonists. This grant supports mechanism of action studies of folate inhibitors of dihydrofolate reductase and thymidylate synthase Department of Medicine Research Grant-RWJMS-UMDNJ (PI) 2005-2006 Mechanism of Translational Regulation of Dihydrofolate Reductase Type-Research grant

BIOGRAPHICAL SKETCH Provide the following information for the key personnel and other significant contributors.

Follow this format for each person. DO NOT EXCEED FOUR PAGES.

NAME Axelrod, David E. eRA COMMONS USER NAME Axelrod

POSITION TITLE Professor of Genetics

EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)

INSTITUTION AND LOCATION DEGREE (if applicable) YEAR(s) FIELD OF STUDY

University of Chicago B.S. 1962 Physics University of Tennessee, Knoxville & Oak Ridge Ph.D. 1967 Microbial Genetics Albert Einstein College of Medicine, Bronx,NY Postdoc Molecular Biology

A. Positions

1968-1970 Postdoctoral Fellow, Dept Develop Biol & Cancer, Einstein Coll Med, Bronx, NY 1970-1976 Assistant Professor, Dept Biological Sciences, Rutgers University, New Brunswick, NJ 1976-1977 Research Biologist (Sabbatical), Molecular Hematology Branch, NIH, Bethesda, MD 1976-1983 Associate Professor, Dept Biological Sciences, Rutgers University, Piscataway, NJ 1983-1997 Associate Professor, Waksman Inst Microbiol & Dept Biol Sci, Rutgers University

1993-1998 Coordinator, Computational Molecular Biology Graduate Program, Rutgers University 1997-2001 Associate Professor, Dept Genetics, Rutgers University, Piscataway, NJ 2001- Professor, Dept Genetics, Rutgers University, Piscataway, NJ 2001- Professor, Molecular Biosciences Graduate Program, Rutgers University

Other 1976- Faculty, Grad Sch Biomed Sci, Robert Wood Johnson Med School, Piscataway, NJ 1991-93 Secretary, Cell Kinetics Society 1991- Member, Ctr Discrete Math & Theoretical Computer Sci (DIMACS), Rutgers University 1995- Member, Cancer Institute of New Jersey (CINJ), New Brunswick, NJ

B. Selected peer-reviewed publications (in chronological order) (Total peer reviewed = 55) 1. Kuczek, T. and D.E. Axelrod. 1986. The importance of clonal heterogeneity and interexperiment variability

in modeling the eukaryotic cell cycle. Math. Biosci. 79:87-96. 2. Axelrod, D.E., F.R. Haider and A.C. Tate. 1986. Distribution of interdivisional times of proliferating and

differentiating Friend murine erythroleukemia cells. Cell Tissue Kinetics 19:547-556. 3. Kuczek, T. and D.E. Axelrod. 1987. Tumor cell heterogeneity: divided-colony assay for measuring drug

response. Proc. Natl. Acad. Sci. USA 84:4490-4494. 4. Axelrod, D.E. and T. Kuczek. 1989. Clonal heterogeneity in populations of normal and tumor cells.

Computers Math. Applic. 18: 871-881. 5. Kimmel, M. and D.E. Axelrod. 1990. Mathematical models of gene amplification with applications to cellular

drug resistance and tumorigenicity. Genetics 125: 633-644. 6. Axelrod, D.E., E. Milcos-Livanos and N. Vibhakar. 1991. Colony size heritability: a new parameter for

characterizing proliferating populations of normal and tumor cells. pp. 713-721. In Mathematical Population Dynamics. (eds.) A. Arino, D.E. Axelrod and M. Kimmel. Marcel Dekker, Inc., NY.

7. Gamel, J. and D.E. Axelrod. 1991. Inheritance and regression toward the mean in proliferating cell populations. Cell Proliferation 24: 281-292.

8. Huang, S. and D.E. Axelrod. 1991. Altered post-translational modification of ras p21 in a transformation-suppressed cell line. Oncogene 6: 1211-1218.

9. Kimmel, M. and D.E. Axelrod. 1991. Unequal cell division, growth and regulation and colony size of mammalian cells: a mathematical model and analysis of experimental data. J. Theoret. Biol. 153: 157-180

10. Kimmel, M., D.E. Axelrod and G. Wahl. 1992. A branching process model of gene amplification following gene deletion from chromosomes. Mutation Res. 276: 225-239.

11. Axelrod, D.E., Y. Gusev, and T. Kuczek. 1993. Persistence of cell cycle times over many cell generations as determined by heritability of colony sizes of ras oncogene-transformed and non-transformed cells. Cell Prolif. 26:235-249.

12. Kimmel, M. and D.E. Axelrod. 1994. Fluctuation test for two-stage mutations: Applications to gene amplification. Mutation Res. 306: 45-60.

13. Axelrod, D.E. , K.A. Baggerly and M. Kimmel. 1994. Gene amplification by unequal sister chromatid exchange: Probabilistic modeling and analysis of drug resistance data. J. Theoret. Biol. 168: 151-159.

14. Gusev, Y. and D.E. Axelrod. 1995. Evaluation of models of inheritance of cell cycle times: computer simulation and recloning experiments. Pp. 97-116. In O. Arino, D.E. Axelrod and M. Kimmel (eds.). Mathematical Population Dynamics: Analysis of Heterogeneity. Vol. 2. Carcinogenesis and Cell & Tumor Genetics. Wuerz Publ. Ltd. Winnipeg.

15. Gusev, Y. and D.E. Axelrod. 1996. Simulation of drug-inhibited cell proliferation with a model of clonal inheritance of cell lifetimes. Pp. 3455-3461. In V. Lakshmikantham (ed.) World Congress of Nonlinear Analysts '92. Walter deGruyter. Berlin.

16. Stivers, D.N., M.K. Kimmel and D.E. Axelrod. 1996. A discrete-time, multi-type generational inheritance branching process model of cell proliferation. Mathematical Biosciences137: 25-50.

17. Axelrod, D.E., Y. Gusev and J.W. Gamel.1997. Ras-oncogene transformed and non-trans-formed cell population are each heterogeneous but respond differently to the chemotherapeutic drug cytosine arabinoside (Ara-C). Cancer Chemotherapy and Pharmacology 39: 445-451.

18. Bat, O., M. Kimmel and D.E. Axelrod. 1997. Computer simulation of expansion of DNA triplet repeats in the fragile X syndrome and Huntington's disease. J. Theoret. Biol.188: 53- 67.

19. Axelrod, D.E. 1997. Nonlinear analysis of tumor cell population dynamics. Pp. 143-154. In Advances in Mathematical Population Dynamics: Molecules, Cells and Man. O. Arino, D. Axelrod, M. Kimmel (eds.), World Sci. Publ. Inc., Singapore.

20. Bat, O., M. Kimmel, and D.E. Axelrod. 1997. Computer simulation of the expansions of CGG DNA triplet repeats in the fragile X syndrome. Pp. 47-68. In Advances in Mathematical Population Dynamics: Molecules, Cells and Man. O. Arino, D. Axelrod, M. Kimmel (eds.), World Sci. Publ. Inc., Singapore.

21. Staudte, R.G., R.M. Huggins, J. Zhang, D.E. Axelrod, and M. Kimmel. 1997. Estimating clonal heterogeneity and interexperiment variability with the bifurcating autoregressive model for cell lineage data. Mathematical Biosciences 143: 103-121.

22. Chapman, J.-A., E. Wolman, S.R. Wolman, Y. Remvikos, S. Shackney, D.E. Axelrod, H. Baisch, I. J. Christensen, R.A. White, L.S. Liebovitch, D.H. Moore, F.M. Waldman, C.J. Cornelisse, T.V. Shankey. 1998. Assessing genetic markers of tumour progression in the context of intra-tumour heterogeneity. Cytometry 31: 67-73.

23. Bat, O., M. Kimmel, and D.E. Axelrod. 1998. Simulation of biochemical contribution to trinucleotide repeat expansion in human hereditary diseases. Math. Modeling and Sci. Computing 9: 105-122.

24. Axelrod, D.E. 2000. A monthly period of symptoms associated with benign prostatic hyperplasia. Urology 55: 436iv-436vi. URL http://www.elsevier.com/locate/urologyonline

25. Subramanian, B. and D.E. Axelrod. 2001. Progression of heterogeneous breast tumors. J. Theoret. Biol. 210: 107-119.

26. Cornélissen, G., D.E. Axelrod, and F. Halberg. 2004. About-weekly variations in nocturia. Biomed. Pharmacother. 58: S140-S144.

27. Sontag, L. and D.E. Axelrod. 2005. Evaluation of pathways for progression of heterogeneous breast tumors. J. Theoret. Biol. 232: 179-189. doi:10.1016/j.jtbi.2004.08.002.

28. Alexe, G., S. Alexe, D.E. Axelrod, P.L. Hammer, and D.J. Weissman. 2005. Logical analysis of diffuse large B-cell lymphomas. Artificial Intell. Med. 34: 235-267.

29. Alexe, G., S. Alexe, D.E. Axelrod, E. Boros, M. Reiss, and P.L. Hammer. 2006. Combinatorial analysis of breast cancer data from gene expression microarrays. Breast Cancer Res 8:R41. doi: 10.1186/bcr1512.

30. Axelrod, R., D.E. Axelrod, and K.J. Pienta. 2006. Evolution of cooperation between tumor cells. Proc. Natl. Acad. Sci. 103:13474-12479. doi/10.1073/pnas.0606053103.

http://www.pnas.org/content/103/36/13474.full.pdf+html?sid=0ee190da-0418-4722-8f14-f55e2b5f51d3 31. Cardiff, R.D., J.P. Gregg, J.W. Miller, D.E. Axelrod, and A.D. Borowsky. 2006. Histopathology as a

predictive biomarker: Strengths and limitations. J. Nutrition 136:2673S-2675S 32. Chapman, J.-A.W., N.A. Miller, H.L.A. Lickley, J. Qian, W.A. Christens-Barry, Y. Fu, Y. Yuan, and D.E.

Axelrod. 2007. Ductal carcinoma in situ of the breast (DCIS) with heterogeneity of nuclear grade:

http://www.elsevier.com/locate/urologyonline

Prognostic effects of quantitative nuclear assessment. BMC Cancer 7:174, doi: 10.1186/1471-2407-7-174, URL http://www.biomedcentral.com/1471-2407/7/174

33. Axelrod, D.E., N.A. Miller, H.L. Lickely J.Qian, W.A. Christens-Barry, Y. Yuan, Y. Fu,. J.-A.W. Chapman. 2008. Effect of quantitative nuclear image features on recurrence of ductal carcinoma in situ (DCIS) of the breast. Cancer Informatics 4: 99-109. URL http://la-press.com/article.php?article_id=583

34. Pienta, K., N. McGregor, R. Axelrod, and D.E. Axelrod. 2008. Ecological therapy for cancer: Defining tumors utilizing an ecosystem paradigm suggests new opportunities for novel cancer treatments. Translational Oncology 1:158-164. doi 10.1593/tlo.08178. PMC2582164

URL http://www.transonc.com/pdf/manuscript/v01i04/neo08178.pdf 35. Axelrod, D.E., N. Miller, and J.-A. Chapman. 2009. Avoiding pitfalls in the statistical analysis of heterogeneous

tumors. Biomedical Informatics Insights 2:11-18. URL http://la-press.com/article.php?article_id=1374 C. Research Support Ongoing Research Support NIH U56 CA 113004 T. Deisboeck (PI) 9/1/04-1/31/10 National Cancer Institute, National Institutes of Health Development of a Virtual Tumor Role: Subcontractor. Collaborator. Will provide, solicit, and coordinate models and data related to tumor cell proliferation, progression and other processes of breast and other cancers. Direct costs: $72,368 Completed Research Support 97-0731 Axelrod (PI) 10/10/97-4/31/01 Hyde and Watson Foundation Computer-aided Diagnosis of Breast Cancer Cells To improve the diagnosis of breast fine needle aspirates by computer-aided image analysis and artificial intelligence. Role: PI 6-49128 Axelrod (PI) Busch Biomedical Research Fund 7/1/02-6/30/03 Quantification of Protein Expression in Breast Cancer Tissue Microarrays To develop image analysis methods and statistical techniques to measure the amount of protein expressed in tissue microarrays of breast cancer specimens. Role: PI 01-1076-CCR-S-0 Axelrod (PI) 6/1/02-5/31/04 State of New Jersey Commission on Cancer Research Quantitative Histopathology of Breast Carcinoma In Situ To provide quantitative nuclear grades of breast DCIS that have improved prognostic value by image analysis and multivariate statistics. Role: PI NSF-IIS-0312953 Hammer (PI), Axelrod (Co-P.I.) 7/1/03-6/30/07 Optimal Support Set Selection in Data Analysis with Applications to Bioinformatics Provide expertise in breast cancer molecular biology and diagnosis, and beta test software for analysis of multiparameter cancer data. Role: Co-PI.

http://www.biomedcentral.com/1471-2407/7/174

http://la-press.com/article.php?article_id=583

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Tamar Barkay Professor

Dept. of Biochemistry and Microbiology Phone: (732) 932 9763 x333 Cook College, Rutgers University e-mail: [email protected] 76 Lipman Dr New Brunswick, NJ 08901 Education: B.Sc.: The Hebrew University, Rehovot, Israel - major in Microbiology, 1974 M.Sc.: Hebrew University, Jerusalem - major in Environmental Health, 1976 Ph.D.: The University of Maryland - major in Microbiology, minor in Biochemistry, 1980 Professional Positions: 2007-present Professor 2003 - 2007 Associate Professor 1999 - 2003 Assistant Professor Dept. of Biochemistry and Microbiology Cook College, Rutgers University 1998 - 1999 Research Associate Professor Center for Environmental diagnostics and Bioremediation The University of West Florida 1996 - 1997 Visiting Scientist Dept. of Molecular Microbiology and Biotechnology Tel-Aviv University, Ramat Aviv 69978 Israel 1984 - 1996 Research Microbiologist, U.S. Environmental Protection Agency Gulf Breeze, Fl 32561 Five publications most closely related to the proposed project: Barkay, T., S. Miller, and A.O. Summers. 2003. Bacterial mercury resistance from atoms to

ecosystems. FEMS Microbiol. Rev. 27:355-384. Schaefer, J.K., J. Yagi, J. Reinfelder, T. Cardona, K. Ellickson, S. Tel-Or, and T.

Barkay. 2004. The role of the bacterial organomercury lyase (MerB) in controlling methylmercury accumulation in mercury contaminated natural waters. Env. Sci. Technol. 38:4304-4311. Faculty of 1000 “recommended” citation

Poulain, A.J. S.M. Ní Chadhain, P.A. Ariya, M. Amyot, E. Garcia, P.G.C. Campbell, G.J. Zylstra, and T. Barkay. 2007. Potential for mercury reduction by microbes in the high Arctic. Appl. Environ. Microbiol. 73: 2230–2238. Faculty of 1000 “must read” citation

Kritee, K., T. Barkay, and J.D. Blum. 2009. Mass dependent stable isotope fractionation of mercury during microbial degradation of methylmercury. Geochim. Cosmochim. Acta. 73:1285-1296

Wiatrowski, H.A. S. Das, R. Kukkadapu, E. Ilton, T. Barkay, and N. Yee. 2009. Reduction of Hg(II) to Hg(0) by Magnetite. Env. Sci & Technol. 42:5307-5313. Science July 3rd, 2009 “editor’s choice” selection”

Five other publications: Vetriani, C., Y.S., Chew, S.M. Miller, J. Yagi, R.A. Lutz, and T. Barkay. 2005. Mercury adaptation among bacteria from a deep-sea hydrothermal vent. Appl. Enviorn. Microbiol.

71:220-226. Kritee K., J. Blum, M. Johnson, B. Bergquist, and T. Barkay. 2007. Mercury stable isotope

fractionation during reduction of Hg(II) to Hg(0) by mercury resistant microorganisms. Env. Sci. & Technol. 41:1889-1895. 2007 most cited paper in ES&T

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Wang, Y., Z. Freedman, P. Lu-Irving, R. Kaletsky, and T. Barkay. 2009. An initial characterization of the mercury resistance (mer) system of the thermophilic bacterium Thermus thermophilus HB27. FEMS Microbiol. Ecol. 67:118-129

Crespo-Medina, M., A.D. Chatziefthimiou, N.S. Bloom, G.W. Luther III, D.D. Wright, J.R. Reinfelder, C. Vetriani, and T. Barkay. 2009. Adaptation of chemosynthetic microorganisms to elevated mercury concentrations in deep-sea hydrothermal vents. Limnol. Ocaenog. 54:41-49

Barkay. T., K. Kritee, E. Boyd, and G. Geesey. A thermophilic bacterial origin and subsequent constraints by redox, light, and salinity on the evolution of the microbial mercuric reductase. Environ. Microbiol. Accepted for publication.

Synergistic activities Co-organizer of a 3 days workshop on Horizontal Gene Transfer in Microbial

Communities (NSF/DOE) - June 2004 Co-organizer of conference sessions: “Mercury biogeochemistry” (Mercury as a Global

Pollutant 2006 conference, Madison, WI - Aug. 2006); “Interactions of microorganisms with metals in geothermal environments” (109th ASM Annual Meeting, Philadelphia, PA May 2009); “Microbial Cycling of Toxic Elements (eg. As, Se, Hg, Te) in Extreme Environments” (Goldschmidt 2009, Davos, Switzerland, June 2009)

Editorial board membership: Applied and Environmental Microbiology (1990-1996, 2006- present FEMS Microbiology Ecology (2006-present); Faculty of 1000 (2005–present)

Panel member: NSF/OEI (2009), NSF/MIP (2004, 2006, 2007), DOE/Genomes to Life Program (2004, 2005), DOE/Micorbial Genomes (2003), DOE/NABIR (2001)

Course development and teaching: “Microbial Ecology and Biodiversity” lecture course for undergraduate/graduate students (2000-Present); Microbial Ecology and Biodiversity lab course for undergraduate/graduate students (2006-Present)

Collaborators: Mark Hines, Carol Kelly, Niels Kroer, John Reinfelder, John Rudd, Søren Sørensen, Costantino Vetriani, Barth Smets, Charley Driscoll, Stefan Grimberg, Michael swift, Joel Blum, Marc Amyot, Gill Geesey, Nathan Yee Graduate and postgraduate advisors: R.R. Colwell (graduate), V. Daniel (deceased), B.H. Olson. Postdoctoral associates and students: E. Sauter, S. Nazaret, J. Letowski, J. Coombs, H. Wiatrowski, Y. Wang, Chu-Ching Lin (postdoc’s), J. Kurtz, L. Rassmusen, J. de Lipthay, S. Sørensen, J. Schaefer, K. Kritee, A. Chatziefthimiou, S. Hicks, R. Ward, M. Crespo-Medina, Z. Friedman, Riqing Yu, Annette Møller, Kim Cruz.

BIOGRAPHICAL SKETCH Provide the following information for the Senior/key personnel and other significant contributors.


NAME Belden, William J. eRA COMMONS USER NAME (credential, e.g., agency login) WJBELDEN

POSITION TITLE Assistant Professor of Biochemistry and Microbiology

EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable.)

INSTITUTION AND LOCATION DEGREE (if applicable) MM/YY FIELD OF STUDY

University at Buffalo, Buffalo, NY BS 05/90 Aerospace Engineering Bennington College, N/A 06/92 Biology

Dartmouth College, Hanover, NH Ph.D. 06/02 Molecular & Cellular Biology

University of Pennsylvania, Philadelphia, PA Postdoctoral 01/03 Biochemistry Dartmouth Medical School Postdoctoral 08/09 Genetics

A. Personal Statement The goal of this proposal is to further characterize the role of epigenetics and chromatin remodeling in circadian regulated gene expression. Specifically, I propose genome-wide studies in conjunction with biochemical experiments to understand how the amplitude and timing of circadian gene expression is controlled via a subset of chromatin-remodeling enzymes. As a post-doctoral fellow, I spear-headed a program to examine chromatin-remodeling and epigenetics in a circadian biology in lab. At the time, there were no chromatin remodeling protocols in place in this specific lab, and no one in the lab was working along these lines. This left me with the daunting task of developing and troubling shooting numerous assays to study chromatin biology including; Chromatin Immunoprecipation (ChIP), MNase I assays, Ligation Mediated PCR, movement of mononucleosomes and DNA methylation analysis, to name a few. The fact that I was able to trouble shoot all of these assays is a tribute to my abilities as a scientist. Moreover, I managed to tackle a problem that at the time, no one was exploring in Neurospora. This created a nice little niche that I can continue now that I am a junior faculty. My work as a graduate student involved working in a reconstituted, in vitro, cell free system, making me uniquely qualified to perform the biochemical characterization studies outlined in the proposal. As a result of this experience, I am quite suited to continue working along these lines and expand the program to genome-wide and biochemical analyses. The experiments outlined in this proposal are a direct off-shoot of my post-doctoral work and the logical next step. I have gone to the effort to secure outside assistance where needed (see support letters) and have arranged to have the sequencing costs covered. Finally, there is strong support at Rutgers University for junior faculty plus, a talented pool of graduate students and post-doctoral fellows, collectively making it a scholarly environment where quality science is not only expected, but achieved. B. Positions and Honors Positions and Employment 1992-1995 Research Technician, Infectious Disease Unit, Massachusetts General Hospital, Samuel I.

Miller, M.D. 1995-1997 Research Technician, Department of Biochemistry, Dartmouth Medical School, Charles

Barlowe, Ph.D. 1997-2001 Graduate Student, Department of Biochemistry, Dartmouth Medical School, Charles Barlowe,

Ph.D. 2001-2002 Research Fellow, Department of Biochemistry and Biophysics, University of Pennsylvania,

P.Leslie Dutton, Ph.D. 2003-2009 Research Fellow, Genetics Department, Dartmouth Medical School, Jay C. Dunlap, Ph.D.

BIOGRAPHICAL SKETCH Provide the following information for the Senior/key personnel and other significant contributors in the order listed on Form Page 2.


NAME Bhanot, Gyan eRA COMMONS USER NAME (credential, e.g., agency login) GBHANOT

POSITION TITLE Professor (Rutgers University.)



M. S. University of Baroda, India B.Sc. 1968-1972 Phys., Math. Stat. Indian Institute of Technology, Bombay, India M.S. 1972-1974 Physics SUNY, Stonybrook M.A. 1974-1975 Physics Cornell University Ph.D. 1975-1979 Theoretical Physics

A. Personal statement: For the last eight years, the principal focus of my research has been the analysis of

high throughput data to understand biological pathways disrupted in cancers of the breast and kidney. The goal of my work is to identify biomarkers associated with risk of recurrence, drug resistance and metastasis. From my previous experience at IBM Research, I also have considerable expertise in using web based software tools, developing novel algorithms, code optimization and parallel programming. My training in Physics, Mathematics and Statistics has also given me the necessary analytical background to design an appropriate study and use/develop the necessary statistical methods/tools to analyze the data.

B. Positions and Honors. Honors, Awards and Memberships 1. 2006 Supercomputing Gordon Bell Award for paper titled: ‘The BlueGene/L Supercomputer and

Quantum Chromodynamics’, in the category, “Special accomplishment for innovation in scalable implementation’.

2. Referee for: Biophysics Journal, PNAS, SIAM, AACR, J of HPC, Human Genetics, BMC Bioinformatics, BMC Genetics, Transactions on Parallel and Distributed Systems, Genomics, Nucl. Acid Research.

Professional Experience 1979-1981 Post-doc, Physics Department, Brookhaven National Labs. 1981-1982 1983-1984, Member, Institute for Advanced Study, Princeton, NJ 1982-1983 Post-doc, European Center for Nuclear Research (CERN), Geneva, Switzerland 1984-1985 Post-doc, Institute for Theoretical Physics, UCSB, Santa Barbara 1985-1987 Senior Scientist, Supercomputer Institute, Florida State University 1987-1989 Associate Professor, Physics Department, Florida State University 1989-1994 Senior Scientist, Thinking Machines Corporation, Cambridge, MA 1994-2006 Research Staff Member, IBM Research, Yorktown Heights, NY 2001-2002 Visiting Professor, Molecular Biology, Princeton University 2006-2008 Professor, Biomedical Eng. & BioMaPS Institute, Rutgers University 2002-present Visiting Member, Systems Biology, Institute for Advanced Study, Princeton, NJ 2006-present Member, Cancer Institute of New Jersey, New Brunswick, NJ 2008-present Professor, Department of Molecular Biology and Biochemistry; Department of Physics and

BioMaPS Institute, Rutgers University Other Experience and Professional Memberships 2007-present, Member, Cancer Institute of New Jersey IT Advisory Committee 2001-present, Adjunct Professor, Bioinformatics Program, Boston University


Patents: 1. YOR8-2001-1004, Dense matrix inversion using class functions. Filed 8/21/2001. 2. YOR8-2001-1007, FFT Algorithm on Torus. Filed 8/21/2001. 3. YOR8-2001-1008, Global Arithmetic function in Torus. Filed 08/21/2001. 4. YOR8-2004-0333, Optimizing Communication Layout for Applications on the Blue Gene Supercomputer.

Filed 05/10/2004, 5. YOR8-2005-0024, A Robust Classification Strategy for Cancer Detection from Mass Spectrometry Data,

Filed 01/10/2005 6. YOR8-2006-0476, Robust Cluster Discovery by Principal Component Analysis and Unsupervised

Consensus Ensemble Clustering, Submitted, 2007.

C. Peer-reviewed Journal Papers (most relevant from ~ 130) 1. Liu H, Brannon AR, Reddy A, Alexe G, Seiler M, Arreola A, Oza J, Yao M, Juan D, Liou L, Ganesan S,

Levine AJ, Rathmell WK, Bhanot G. Identifying direct mRNA targets of microRNA dysregulated in cancer: with application to clear cell Renal Cell Carcinoma. 2009, BMC Systems Biology, in press.

2. Brannon AR, Reddy A, Seiler M, Arreola A, Moore DT, Pruthi RS, Wallen EM, Nielsen ME, Liu H, Ljungberg B, Zhao H, Brooks JD, Nathanson KL, Ganesan S, Bhanot G, Rathmell WK. Molecular Stratification of Clear Cell Renal Cell Carcinoma by Consensus Clustering Reveals Distinct Subtypes and Survival Patterns. Genes and Cancer 2010, 1(2):152–63.

3. Juan D, Alexe G, Antes T, Liu H, Madabhushi A, Delisi C, Ganesan S, Bhanot G, Liou LS. Identification of a MicroRNA Panel for Clear-cell Kidney Cancer. Urology 2010, 75(4):835:841.

4. Seiler M, Huang CC, Szalma S, Bhanot G. ConsensusCluster: a software tool for unsupervised cluster discovery in numerical data. OMICS 2010, 14(1):109-113.

5. Norton K-A, Wininger M, Bhanot G, Ganesan S, Barnard N, Shinbrot T. A 2D Mechanistic Model of Breast Ductal Carcinoma in Situ (DCIS) Morphology and Progression. 2009, Journal of Theoretical Biology 2010, 263(4):393-406.

6. Mathew R, Karp C, Beaudoin B, Vuong N, Chen G, Chen HY, Bray K, Reddy A, Bhanot G, Gelinas C, DiPaola RS, Karantza-Wadsworth V, White E. Autophagy suppresses tumorigenesis through elimination of p62. 2009, Cell 137, 1062:1075. PMCID: PMC2802318.

7. Alexe A, Vijaya-Satya R, Seiler M, Platt D, Bhanot T, Hui S, Tanaka M, Levine AJ, Bhanot G. PCA and Clustering Reveal Alternate mtDNA Phylogeny of N and M Clades. 2008, J. Mol Evol, 67 (5), 465-487. PMID: 18855041.

8. Bilal E, Rabadan R, Alexe A, Fuku N, Ueno H, Nishigaki Y, Fujita Y, Ito M, Arai Y, Hirose N, Ruckenstein A, Bhanot G, Tanaka M. Mitochondrial DNA Haplogroup D4a is a Marker for Extreme Longevity in Japan. 2008, PLoS ONE, 3(6): e2421. doi:10.1371/journal.pone.0002421. PMCID: PMC2408726

9. Greenbaum BD, Levine AJ, Bhanot G, Rabadan R. Patterns of Evolution and Host Gene Mimicry in Influenza and Other RNA Viruses.2008, PLoS Pathogens 4(6):e1000079 doi:10.1371/journal.ppat.1000079. ] PMCID: PMC2390760

10. Alexe G, Dalgin GS, Scanfeld D, Tamayo P, Mesirov J, Delisi C, Harris L, Bernard N, Martel M, Levine AJ, Ganesan S, Bhanot G. High Expression of Lymphocyte Associated Genes in node-negative HER2+ breast cancer correlates with lower recurrence rates. 2007, Cancer Research, 67, 10669:10676. PMID: 18006808

11. Dalgin GS, Alexe G, Scanfeld D, Tamayo P, Mesirov J, Ganesan S, DeLisi C, Bhanot G. Portraits of Breast Cancer Progression. 2007, BMC Bioinformatics 8:291. PMCID: PMC1978212

12. Alexe G, Dalgin GS, Scanfeld D, Tamayo P, Mesirov J, Ganesan S, Bhanot G, DeLisi C. Breast Cancer Stratification from Analysis of Micro-array data of Micro-dissected Specimens. 2007, Proceedings of the IBSB 2007, Genome Informatics Series, Vol. 18, Jan 2008, World Scientific: ISBN 978-1-86094-991-3. PMID: 18546481.

13. Alexe G, Dalgin GS, Ramaswamy R, DeLisi C, Bhanot G. Data Perturbation Independent Diagnosis and Validation of Breast Cancer Subtypes Using Clustering and Patterns. 2006, Cancer Informatics 2, 243:274. PMCID: PMC2675483.


14. Alexe G, Fuku N, Bilal E, Ueno H, Nishigaki Y, Fujita Y, Ito M, Arai Y, Hirose N, Bhanot G, Tanaka M. Enrichment of Longevity Phenotype in mtDNA Haplogroups D4b2b, D4a and D5 in the Japanese Population. 2007, Human Genetics 121(3-4),347:356. PMID: 17308896.

15. Vijaya-Satya R, Mukherjee A, Alexe G, Parida L, Bhanot G. Constructing Near-Perfect Phylogenies with Multiple Homoplasy Events. 2006, Bioinformatics, 22(14),514:522. PMID: 16873515

16. Bhanot G, Alexe G, Levine AJ, Stolovitzky G. Robust diagnosis of non-Hodgkin lymphoma phenotypes validated on gene expression data from different laboratories. 2005, Genome Informatics 16(1): 233:244, PMID: 16362926

17. Bhanot G,Alexe G, Venkataraghavan B, Levine AJ. A robust meta-classification strategy for cancer detection from mass spectrometry data. 2005, Proteomics 6(2),592:604. PMID: 16447989

Book Chapters/Books Edited: 1. Reddy A, Kronek L-P, Brannon AR, Seiler M, Ganesan S, Rathmell WK, Bhanot G. Predicting Cancer

Survival Using Expression Patterns. 2009, In Medical Bioinformatics: Statistical Analysis of Complex Diseases. in press.

2. Alexe G, Monaco J, Doyle S, Basavanhally A, Reddy A, Seiler M, Ganesan S, Bhanot G, Madabhushi A. Towards Improved Cancer Diagnosis and Prognosis using Analysis of Gene Expression Data and Computer Aided Imaging. In ‘Experimental Biology and Medicine,’ (Maywood), 2009.

3. Bhanot G and Walkup R. Pthreads Programming and Optimization.Chapter 4, IBM Redbook SG24-5611-00: ‘Scientific Applications in RS/6000 SP Environments’, 1999.

4. Bhanot G, Sonnad V, Tamirisa CG. Mixed Models with Pthreads and MPI. In ‘Industrial Strength Parallel Computing,’ Ed. Alice Koniges, Morgan Kaufman Publishers, October, 1999.

5. Bhanot G. Resolution of Some Paradoxes in B-Cell Binding to Antigen: A Computer Study. In ‘New Directions in Statistical Physics: Econophysics, Bioinformatics, and Pattern Recognition’ Springer -DE-ISBN:3540431829, 2004, XVII Edition, Ed. L.Wille.

D. Research Support. Current: 1. PI. Startup Grant from CINJ: 09/01/06-08/31/11. Goal: Work on Bioinformatics of Cancer Risk and

Progression using SNP, mRNA, microRNA expression and sequence data. 2. PI. NJCCR Seed Grant. RT-PCR Assay for Breast Cancer Subtypes: 07/01/08-06/30/10. Goal:

Develop an RT-PCR assay for FFPE sections to stratify breast cancer patients into risk classes. 3. PI. J&J/Centocor Research Agreement: “Understanding Disease Initiation, Progression and Metastasis

and Identifying Markers for Drug Efficacy by developing and using Bioinformatics Tools and Methods: 06/15/08–06/14/10. Goal: Identify drug sensitivity signatures for oncological and immunological diseases using high throughput data.

4. co-PI. (PI S. Ganesan, MD, PhD, CINJ) CINJ R&D Award. Understanding the nature of the immune infiltrate in a subset of HER2+ breast cancers: 06/30/09-05/31/10. Goal: Use gene expression analysis to look for possible causes for the observed infiltration of T and B cells into a subset of HER2+ tumors. Pending:

1. R01 – NIH. Role: co-PI (PI: Dr. S. Ganesan, CINJ). Title: 53BP1 Abnormalities in Breast Cancer: 07/01/2010 – 06/30/2015. Goal: identify the mechanism of 53BP1 loss in cell lines and clinical samples using Northern blots, cDNA sequencing, genomic sequencing, methylation status and Protein/mRNA stability analysis. In cell lines: determine sensitivity of 53BP1-/- cells to PARP inhibitors, and rescue with induction of wildtype 53BP1; determine if 53BP1 loss allows tolerance of BRCA1 loss. In human subjects: study if 53BP1 loss correlates with response to platinum and PARP inhibitors in a neoadjuvant platinum trial, metastatic platinum trial and a neoadjuvant PARP inhibitor trial, all currently underway at CINJ.

2. R21 – NCI. Role: PI. (co-PI: Dr. S. Ganesan, CINJ). Title: miRNA and mRNA dysregulation in early progression of Luminal A breast cancer. 07/01/2010-06/30/2012. Goal: To understand the molecular


and genetic basis of the dysregulation in miRNA control of mRNA in early breast cancer progression by Illumina sequencing of all highly expressed mRNA and miRNA transcripts.

3. R21 – NCI. Role: co-PI. (PI: Dr. W.K. Rathmell, Univ. of North Carolina Med Sch.) Title: mRNA/microRNA dysregulation and SNP specificity in ccRCC progression. 07/01/2010-06/30/2012. Goal: To understand the molecular and genetic basis of dysregulation in miRNA control of mRNA in clear cell renal cell carcinoma by Illumina sequencing of all highly expressed mRNA and miRNA transcripts.

Name: ELISABETTA BINI Position Title: Assistant Professor, Dept. of Biochemistry and Microbiology (a) Education and Training Institution Field Degree Year University of Nebraska, Lincoln, NE Microbiology Ph.D. 2001 University of Pisa (Italy) Protistology Doctorate 1994 University of Pisa (Italy) Biology Laurea 1988 (b) Research and Professional Experience Positions and Employment 2004-present Assistant Professor, Rutgers University – Dept. of Biochemistry and Microbiology –

New Brunswick, NJ. 2001-2003 Post-doctoral fellow, Tufts University – Dept. of Biomedical Engineering – Medford,

MA. 1994-1995 Post-doctoral fellow, University of Nebraska – Dept. of Chemistry – Lincoln, NE. Other Experience and Professional Memberships 2006-present Member, International Society for Extremophiles 2004-present Member, Theobald Smith Society 2004-2006 Local Councilor of the Theobald Smith Society, New Jersey Branch of ASM 1996-present Member, American Society of Microbiology (c) Publications (10 most recent): Bini E. 2010. Archaeal transformation of metals in the environment. FEMS Microbiology Ecology. (In press)

Villafane, A., Y. Voskoboynik, M. Cuebas, I. Ruhl and E. Bini. (2009). Response to excess copper in the hyperthermophile Sulfolobus solfataricus strain 98/2. Biochemical and Biophysical Research Communications. 385:67-71.

Ecology, Archaea, and Biomacromolecules. Bini E. (2008) Archaea-metal interactions: metabolism and strategies of resistance. In: Blum, P. (ed.), Archaea: New models for prokaryotic biology. Caister Academic Press, Norwich, UK , pp. 27-43.

Chae, J.-C., Kim E., Bini E. and Zylstra G.J. (2007) Comparative analysis of the catechol 2,3-dioxygenase gene locus in thermoacidophilic archaeon Sulfolobus solfataricus strain 98/2. Biochemical and Biophysical Research Communications. 357:815-819.

Bini, E., Wong Po Foo C., Huang J., Karageorgiou V., Kitchel B. and Kaplan D.L. (2006) RGD-functionalized bioengineered spider dragline silk biomaterial. Biomacromolecules. 7:3139-3145.

Wong Po Foo C., Bini E., Hensman J., Knight D.P., Lewis R.V. and Kaplan D.L. (2006) Role of pH and charge on silk protein assembly in insects and spiders. Appl. Phys. A 82:223-233.

Dixit V., Bini E., Drozda M. and Blum P. (2004) Mercury inactivates transcription and the general transcription factor, TFB in the archaeon Sulfolobus solfataricus. Antimicrobial Agents & Chemotherapy. 48: 1993-1999.

Hoang V., Bini E., Dixit V., Drozda M., Blum P. (2004) The role of cis-acting sequences governing catabolite repression control of lacS expression in the archaeon Sulfolobus solfataricus. Genetics. 167:1563-1572.

Bini E., Knight D. P. and Kaplan D. L. (2004) Mapping domain structures in silks from insects and spiders related to protein assembly. J. Mol. Biol. 335: 27-40.

Bini, E., V. Dikshit, K. L. Dirksen, M. Drozda, and P. Blum. (2002) Stability of mRNA in the hyperthermophilic archaeon Sulfolobus solfataricus. RNA 8:1129-1136.

(d) Sinergistic Activities • Participated in the Genome Sequence Annotation Workshop with the Lysobacter group, at the

Joint Craig Venter Institute (JCVI) on Aug 2007, Rockville, MD.

• Reviewer for the journals: Biodegradation, FEMS Microbiology, Journal of Bacteriologgy, Archaea, Biomacromolecules.

• Ad hoc reviewer for: University of Puerto Rico Sea Grant College Program National Science Foundation (NSF) The U.S.-Israel Binational Agricultural Research and Development Fund (BARD)

Air Force Office of Scientific Research (AFOSR)

• Panelist for the the U.S. Department of Energy/Environmental Remediation Science Program

• Development of new undergraduate course, Microbial Genetics and Genomics in 2006.

(e) Collaborations and Other Affiliations (i) Collaborators and Co-Editors Paul Blum, University of Nebraska at Lincoln, NE; Jong-Chan Chae, Rutgers University, New Brunswick, NJ; J. Hensman, Oxford University, UK; Maryam Honarbakhsh, Rutgers University, New Brunswick, NJ; Jia Huang, Tufts University, Medford, MA; David Kaplan, Tufts University, Medford, MA; Vassili Karageorgiou, Tufts University, Medford, MA; Eungbin Kim, Rutgers University, New Brunswick, NJ; Brandon Kitchel, Tufts University, Medford, MA; David Knight, Oxford University, UK and Spinox Ltd., Newbury, UK; S Y Lee, Korean Advanced Institute of Sci. and Technology, Daejeon, Korea; R. V. Lewis, University of Wyoming, Laramie, WY; Yukari Maezato, University of Nebraska at Lincoln, NE; Michelle McBride, Rutgers University, New Brunswick, NJ; Maina Mentz, Rutgers University, New Brunswick, NJ; Madhavi Parikh, Rutgers University, New Brunswick, NJ; Ilona Ruhl, Rutgers University, New Brunswick, NJ; Regina Valluzzi, Tufts University, Medford, MA; Brian Vernaglia, Tufts University, Medford, MA; Aramis Villafane, Rutgers University, New Brunswick, NJ; Yekaterina Voskoboynik, Rutgers University, New Brunswick, NJ; Cheryl Wong Poo Fo, Tufts University, Medford, MA; Nathan Yee, Rutgers University, New Brunswick, NJ; Gerben Zylstra, Rutgers University, New Brunswick, NJ

(ii) Graduate and Postdoctoral Advisors Paul Blum, U of Nebraska at Lincoln, NE; David Kaplan, Tufts University, Medford, MA

(iii) Graduate Student Advisee’s Aramis Villafane, Microbiol. Mol. Gen. (Ph.D. 2009); Mariola Cuebas, Microbiol. Mol. Gen. (M.S. 2009); Maryam Honarbakhsh, Microbiol. Mol. Gen. 2009-pres; Kenneth Frankenbush Jr., Microbiol. Mol. Gen. 2009-pres.



BIOGRAPHICAL SKETCH Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2.


NAME BREWER, Gary eRA COMMONS USER NAME (credential, e.g., agency login) BREWERGA

POSITION TITLE Professor



Auburn University, Auburn, AL B.S. 1976 Physics Vanderbilt Univerwity, Nashville, TN Ph.D. 1984 Biochemistry McArdle Lab., Univ. of Wisconsin, Madison, WI Postdoc 1984-1989 Molecular Biology

Please refer to the application instructions in order to complete sections A, B, and C of the Biographical Sketch. Positions: 1989-1997 Assistant Professor Wake Forest Univ. Sch. Med. - Microbiology and Immunology 1997-1999 Associate Professor Wake Forest Univ. Sch. Med. - Microbiology and Immunology 1999-2004 Associate Professor UMDNJ, R.W. Johnson Med. Sch. - Mol. Genetics, Micro., Immuno. 2004-present Professor UMDNJ, R.W. Johnson Med. Sch. - Mol. Genetics, Micro., Immuno. Awards and Professional Activities: Cellular and Molecular Biology Predoctoral Training Grant, NIH, 1981; Tumor Biology Postdoctoral Training Grant, NIH, 1984; American Cancer Society Study Section on Genetic Mechanisms in Cancer, Ad hoc reviewer, 1991-1996, Regular Member 1997-2000; Member of American Cancer Society Experts Directory, 2000-present; NIH Ad hoc reviewer for SBIRs, 1999; NIH Ad hoc reviewer for CDF-1, 2002, 2003; MGB, 2005; MGB Regular Member 2007-2011; FASEB MARC Travel Award to attend ABRCMS in New Orleans, LA, 2002; Elsie Eggert/American Heart Association Research Fellow, 2002-2005. Guest editor, Methods: MicroRNAs Part A, vol. 43, no. 2, October 2007 Selected Publications (peer-reviewed since 2004): Donnini, M., Lapucci, A., Papucci, L., Witort, E., Jacquier, A., Brewer, G., Nicolin, A., Capaccioli, S., and

Schiavone, N. 2004. Identification of TINO - A new evolutionarily conserved BCL-2 AU-rich element RNA-binding protein. J. Biol. Chem. 279: 20154-20166.

Liao, B., Patel, M., Hu, Y., Charles, S., Herrick, D.J., and Brewer, G. 2004. Targeted knockdown of the RNA-binding protein CRD-BP promotes cell proliferation via an IGF-II-dependent pathway in human K562 leukemia cells. J. Biol. Chem. 279: 48716-48724.

Liao, B., Hu, Y., Herrick, D.J., and Brewer, G. 2005. The RNA-binding protein IMP-3 is a translational activator of insulin-like growth factor II leader-3 mRNA during proliferation of human K562 leukemia cells. J. Biol. Chem. 280: 18517-18524.

Sommer, S., Cui, Y., Brewer, G., and S.A.W. Fuqua. 2005. The c-Yes 3’-UTR contains adenine/uridine-rich elements that bind AUF1 and HuR involved in mRNA decay in breast cancer cells. Steroid Biochem.Mol. Biol. 97: 219-229.

Lal, A., Abdelmohsen, K., Pullman, R., Kawai, T., Yang, X., Brewer, G., and Gorospe, M. 2006. Posttranscriptional derepression of GADD45α by genotoxic stress. Mol. Cell 22: 117-128.

Brewer, G. and Chesoni, S.A. 2006. hnRNP D. AfCS-Nature Molecule Page (doi:10.1038/mp.a003244.01).



Banihasmemi, L., Wilson, G.W., Das, N., and Brewer, G. 2006. Upf1/Upf2 regulation of 3’ untranslated region splice variants of AUF1 links nonsense-mediated and A+U-rich element-mediated mRNA decay. Mol. Cell. Biol, 26: 8743-8754.

Liao, B., Hu, Y., and Brewer, G. 2007. Competitive binding of AUF1 and TIAR to MYC mRNA controls its translation. Nature Struct. Mol. Biol., 14: 511-518.

Sinsimer, K.S., Gratacos, F.M., Knapinska, A.M., Lu, J., Krause, C.D., Wierzbowski. A.V., Maher, L.R., Scrudato, S., Rivera, Y.M., Gupta, S., Turrin, D.K., De La Cruz, M.P., Pestka, S., and Brewer, G. 2008. Chaperone Hsp27, a novel subunit of AUF1 protein complexes, functions in AU-rich element-mediated mRNA decay. Mol. Cell. Biol. 28: 5223-5237.

Sarkar, S., Sinsimer, K.S., Foster, R.L., Brewer, G., and Pestka, S. 2008. AUF1 isoform-specific regulation of anti-inflammatory IL10 expression in monocytes. J Interferon Cytokine Res. 28: 679-692.

Bu, Y., Lu, C., Bian, C., Wang, J., Li, J., Zhang, B., Li, Z., Brewer, G., and Zhao, R.C. 2009. Knockdown of Dicer in MCF-7 human breast cancer carcinoma cells results in G1 arrest and increased sensitivity to cisplatin. Oncol. Rep. 21: 13-17.

Recent reviews/technical articles (since 2004): Knapinska, A.M., Irizarry-Barreto, P., Adusumalli, S., Androulakis, I., and Brewer, G. 2005. Molecular

mechanisms regulating mRNA stability: Physiological and pathological significance. Curr. Genomics 6: 471-486.

Gupta, M. and Brewer, G. 2006. MicroRNAs: New players in an old game. Proc. Natl. Acad. Sci. USA 103: 3951-3952.

Brewer, G. MicroRNAs – Discovery, analyses, targets. In: Methods: MicroRNAs Part A, editor G. Brewer, 2007; 43: 89-90.

Ysla, R., Wilson, G.M., and Brewer, G. 2009. Assays of adenylate uridylate-rich element-mediated mRNA decay in cells. Meth. Enzymol., 449: 47-71.

Research Ongoing or Completed During Last 3 Years: Ongoing “Posttranscriptional Regulation of Oncogene Messenger RNA” Principal Investigator: Gary Brewer, Ph.D. Agency: NIH/NCI Type: R01 (CA052443, Years 15-19) Period: August 8, 2008 to June 30, 2013 The goals of this project are to examine mechanisms of AUF1-directed translational activation and examine differential, AUF1-dependent association of trans-acting factors, including microRNAs, with degraded versus translationally-regulated ARE-mRNAs. . “Role of mRNA Decay in the Immune System” (Project #1: “Adherence Activated Monocyte Genes”) Principal Investigator: Sidney Pestka, M.D. (Project #1: Gary Brewer, Ph.D.) Agency: NIH Type: P01 (AI057596, Years 01-05) Period: July 15, 2004 to June 30, 2009 (**one-year, no-cost extension until June 30, 2010**) The goals of this project are to compare the abilities of non-phosphorylated and phosphorylated AUF1 to nucleate assembly of a trans-acting RNA protein complex, examine how the phosphorylation state of AUF1 affects cytokine mRNA degradation, and examine the determinants of AUF1 phosphorylation state in nonadherent and adherent monocytes.

Program Director/Principal Investigator (Last, First, Middle): Brill, Steven J.




NAME Brill, Steven J. eRA COMMONS USER NAME (credential, e.g., agency login) sjbrillnj




University of Maryland, College Park, MD B.S. 1981 Biochemistry SUNY at Stony Brook, Stony Brook, NY Ph.D. 1988 Molecular Biology CSHL, Cold Spring Harbor, NY Post Doc 1992 Biochemistry

A. Positions and Honors.

Positions and Employment 1982-1983 Research Assistant, Lab of Molecular Biology, NCI, NIH, Bethesda, MD (Mentor: M. M. Gottesman). 1983-1988 Graduate Student, SUNY Stony Brook, Stony Brook NY (Mentor: R. Sternglanz). 1988-1992 Postdoctoral Fellow, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY (Mentor: B. Stillman). 1993-1999 Assistant Professor, Department of Molecular Biology and Biochemistry, Rutgers University,

Piscataway, NJ. 1994 - present Member, Cancer Institute of New Jersey 1999 - 2004 Associate Professor, Department of Molecular Biology and Biochemistry, Rutgers University. 2001 - 2004 Acting Chair, Department of Molecular Biology and Biochemistry, Rutgers University. 2003 - 2009 Adjunct Associate Professor, Department of Biochemistry, Robert Wood Johnson Medical

School, UMDNJ. 2004 - present Professor, Department of Molecular Biology and Biochemistry, Rutgers University. Other Experience and Professional Memberships 11/1996 Reviewer, NCI Program Project 1994-2008 Ad hoc Reviewer, NSF 1994-2009 Ad Hoc Reviewer, NIH CDF6 Study Section 2/2000; 2/2001 Ad Hoc Reviewer, NIH CDF2 Study Section 6/2001; 2/2003 Ad Hoc Reviewer, NIH PC Study Section 2004-2008 Regular Member, NIH MGB Study Section Honors 1989 - 1991 National Research Service Award

B. Selected peer-reviewed publications (Selected from 44 peer-reviewed publications). 1. Abraham, I., Brill, S., Hyde, J., Fleischmann, R., Chapman, M., and Gottesman, M. M. (1985). DNA-

mediated gene transfer of a mutant regulatory subunit of cAMP-dependent protein Kinase. J. Biol. Chem. 260, 13934-13940. PMID: 3007543

2. Brill, S. J., and Sternglanz, R. (1988). Transcription-dependent DNA supercoiling in yeast DNA topoisomerase mutants. Cell 54, 403-411. PMID: 2840207

Program Director/Principal Investigator (Last, First, Middle): Brill, Steven J.


3. Brill, S. J., and Stillman, B. (1989). Yeast replication factor-A functions in the unwinding of the SV40 origin of DNA replication. Nature 342, 92-95. PMID: 2554144

4. Philipova, D., Mullen, J. R., Maniar, H. S., Gu, C. and Brill, S. J. (1996). A hierarchy of SSB protomers in Replication Protein-A. Genes Dev. 10, 2222-2233. PMID: 8804316

5. Brill, S. J. and Bastin-Shanower, S.A. (1998). Identification and characterization of the fourth ssDNA binding domain of Replication Protein A. Mol. Cell. Biol. 18, 7225-7234. PMCID: PMC109304

6. Mullen, J. R., Kaliraman, V., Ibrahim, S. S., and Brill, S. J. (2001). Requirement for three novel protein complexes in the absence of the Sgs1 DNA helicase. Genetics, 157, 103-118. PMCID: PMC1461486

7. Fricke, W. M., Kaliraman, V., and Brill, S. J. (2001). Mapping of the DNA topoisomerase III binding domain of the Sgs1 DNA helicase J. Biol. Chem. 276, 8848 - 8855. PMCID: PMC2818744

8. Kaliraman, V., Mullen, J. R., Fricke, W. M., Bastin-Shanower, S.A., and Brill, S.J. (2001). Functional overlap between Sgs1-Top3 and the Mms4-Mus81 endonuclease. Genes Dev. 15, 2730-2740. PMCID: PMC312806

9. Fricke, W.M. and Brill, S.J. (2003). Slx1-Slx4 is a second structure-specific endonuclease that functionally overlaps with Sgs1-Top3. Genes Dev. 17, 1768-1778. PMCID: PMC196184

10. Fricke, W. M., Bastin-Shanower, S. A., Mullen, J. R., and Brill, S. J. (2005). Substrate specificiy of the Mus81-Mms4 endonuclease from S. cerevisiae. DNA Repair, 4, 243-251. PMID: 15590332

11. Mullen, J.R., Nallaseth, F. S., Lan, Y. Q., Slagle, C. E., and Brill, S. J. (2005). Yeast Rmi1/Nce4 controls genome stability as a subunit of the Sgs1-Top3 complex. Mol. Cell. Biol. 25, 4476-4487. PMCID: PMC1140617

12. Ii, T., Mullen, J.R., Slagle, C.E., and Brill, S.J. (2007). Stimulation of in-vitro sumoylation by Slx5-Slx8: evidence for a functional interaction with the SUMO pathway. DNA Repair 6, 1679-1691. PMCID: PMC2100399

13. Ii, T., Fung, J., Mullen, J. R., and Brill, S.J. (2007). The Slx5-Slx8 DNA integrity complex displays ubiquitin ligase activity. Cell Cycle 6, 1-10. PMCID: 2808205.

14. Chen, C-F., and Brill, S.J. (2007). Binding and activation of DNA topoisomerase III by the Rmi1 subunit. J. Biol. Chem. 282, 28971-28979. PMCID: PMC2804875

15. Mullen, J. R. and Brill, S.J. (2008). Activation of the Slx5-Slx8 Ub ligase by poly-SUMO conjugates. J. Biol. Chem. 283, 19912-19921. PMCID: PMC2459270

16. Lu, C.Y., Tsai, C.H., Brill, S.J., and Teng, S.C. (2010). Sumoylation of the BLM ortholog Sgs1, promotes telomere-telomere recombination in budding yeast. Nucleic Acids Res. In Press PMCID: PMC2810998

17. Chen, C-F. and Brill, S.J. (2010). An essential DNA strand exchange activity is conserved in the divergent N-termini of BLM orthologs. EMBO J. In Press.

C. Research Support Ongoing Research Support R01 GM071268-10A2 Brill (PI) 09/30/09 - 06/30/12 NIH/NIGMS Genomic Stability and RecQ DNA Helicases in Yeast. The major goals of this project are (1) to characterize the mechanism of Slx5-Slx8 Ub ligase, (2) to determine the mechanism of Wss1, and (3) to determine the role of poly-SUMOylation in genome stability. Role: PI

Completed Research Support R01 GM067956-05 Brill (PI) 5/01/03 – 4/30/08 NIH/NIGMS Recombination-mediated DNA repair in yeast. The major goals of this project were (1) to determine the structure, regulation, and substrate specificity of the Mus81-Mms4 endonuclease; (2) to determine the role of Mus81-Mms4 endonuclease in known recombination mechanisms; and (3) to identify recombinational repair pathways that interact with or bypass MUS81-MMS4 Role: PI.



NAME Brzustowicz, Linda M eRA COMMONS USER NAME (credential, e.g., agency login) brzustowicz




Harvard University, Cambridge, MA A.B. 1982 Biochemistry Columbia University, New York, NY M.D. 1987 Medicine Brown University, Providence, RI Internship 1987-1988 Pediatrics Columbia University, New York, NY Post-Doc 1988-1991 Molecular Genetics Columbia University, New York, NY Residency 1991-1994 Psychiatry

A. Personal Statement I am a psychiatrist with additional training in molecular and statistical genetics. For the past 16 years I have run the Molecular Psychiatry Laboratory at Rutgers University, focusing primarily on the study of schizophrenia and autism. I have successfully mapped susceptibility loci for both these complex disorders (which have been replicated by other groups) and identified a functional DNA polymorphism at each locus that is associated with increase risk. I have also mapped loci for simple Mendelian disorders (Spinal Muscular Atrophy, Simpson-Golabi-Behmel Syndrome Type II), mapped quantitative traits, and conducted GxE studies. The current application represents the continuation of a 13-year collaborative effort between myself and Dr. Anne Bassett at the University of Toronto to identify genetic factors modulating risk for schizophrenia. Also critical to this application is the statistical methodology contributed by Dr. Veronica Vieland, another long-term (20-year) collaborator. This application builds on the strengths of each of the co-investigators, as well as our long-standing working relationships. For this application, my laboratory will primarily focus on genotyping and linkage and association mapping; I have been conducting such studies for the past 22 years, and have extensive experience with the general principles underlying such studies as well as numerous specific laboratory and analytic techniques that have been developed and utilized over that time period. My laboratory has developed and published the improved Luminex genotyping method that will be used in this project. Over the past five years my laboratory has developed expertise in the analysis of gene expression using post-mortem tissue and cell-culture systems; the limited amount of functional work proposed within this application is therefore also well within my area of expertise. B. Positions and Honors Positions and Employment 1994-2000 Assistant Professor, Center for Molecular and Behavioral Neuroscience, Rutgers University,

Newark, NJ 2000-2005 Associate Professor, Department of Genetics, Rutgers University, Piscataway, NJ 2005- Professor, Department of Genetics, Rutgers University, Piscataway, NJ Other Experience 1994-2008 Member, Rutgers University IRB for the Protection of Human Subjects in Research 1996- Associate Editor, Human Heredity 2000-2008 Chair, Rutgers University IRB for the Protection of Human Subjects in Research 2001-2004 NIH Mammalian Genetics Study Section 2007- Associate Editor, American Journal of Psychiatry 2009-2013 NIMH Initial Review Group, Interventions Committee for Adult Disorders Honors and Awards 1987 Alpha Omega Alpha Medical Honor Society 1987 Lange Medical Award for pre-clinical excellence and Merck Award for overall academic

excellence in medical school

1990 NARSAD Young Investigator Award 1994 New York State Psychiatric Institute Alumni Award for Research 1994 Mead Johnson Travel Fellow to the American College of Neuropsychopharmacology 1995 EJBL Foundation Scholar Research Programme Award 1996 New York State Psychiatric Institute Centennial Award, Alumna of the Decade 2000 NARSAD Independent Investigator Award 2005 NARSAD Staglin Family Music Festival Schizophrenia Research Award

C. Selected Peer-reviewed Publications (Selected from 71 peer-reviewed publications) 1. Brzustowicz LM, Hodgkinson K, Chow EWC, Honer WG, Bassett AS. Location of a Major Susceptibility

Locus for Familial Schizophrenia on Chromosome 1q21-q22. Science 2000; 288:678-682. 2. Wratten NS, Memoli H, Huang Y, Dulencin AM, Matteson PG, Cornacchia MA, Azaro MA, Messenger J,

Hayter JE, Bassett AS, Buyske S, Millonig JH, Vieland VJ, Brzustowicz LM. Identification of a schizophrenia associated functional non-coding variant in NOS1AP. American Journal of Psychiatry, 2009; 166:434-441. NIHMSID181939

3. Xu B, Wratten N, Charych EI, Buyske SG, Firestein BL, Brzustowicz LM. Increased Expression in Dorsolateral Prefrontal Cortex of CAPON in Schizophrenia and Bipolar Disorder. PLoS Medicine 2005; 2:e263. PMCID:PMC1201690

4. Logue MW, Brzustowicz LM, Bassett AS, Chow ECW, Vieland VJ. A Posterior Probability of Linkage (PPL) Based Re-Analysis of Schizophrenia Data Yields Evidence of Linkage to Chromosomes 1 and 17. Human Heredity, 2006; 62:47-54.

5. Carrel D, Du Y, Komlos D, Hadzimichalis NM, Kwon M, Wang B, Brzustowicz LM, Firestein BL. NOS1AP regulates dendrite patterning of hippocampal neurons through a CPE-mediated pathway. The Journal of Neuroscience, 2009; 29:8248-8258. PMCID:PMC2819070

6. Kremeyer B, García J, Kymäläinen H, Wratten N, Restrepo G, Palacio C, Miranda AL, López C, Restrepo M, Bedoya G, Brzustowicz LM, Ospina-Duque J, Arbeláez MP, Ruiz-Linares A. Evidence for a Role of the NOS1AP (CAPON) Gene in Schizophrenia and its Clinical Dimensions: an Association Study in a South American Population Isolate. Human Heredity, 2009; 67:163-73 PMC Journal – In Process

7. Brzustowicz LM, Simone J, Mohseni P, Hayter JE, Hodgkinson KA, Chow EWC, Bassett AS. Linkage Disequilibrium Mapping of Schizophrenia Susceptibility to the CAPON Region of Chromosome 1q22. American Journal of Human Genetics 2004; 74:1057-1063. PMCID:PMC1181969

8. Brzustowicz LM, Mérette C, Xie X, Townsend L, Gilliam TC, Ott J. Molecular and Statistical Approaches to the Detection and Correction of Errors in Genotype Databases. American Journal of Human Genetics 1993; 53:1137-1145. PMCID:PMC1682304

9. Brzustowicz LM, Honer WG, Chow EC, Hogan J, Hodgkinson K, Bassett AS. Use of a Quantitative Trait to Map a Locus Associated with Severity of Positive Symptoms in Familial Schizophrenia to Chromosome 6p. American Journal of Human Genetics 1997; 61:1388-1396. PMCID:PMC1716068

10. Brzustowicz LM, Honer WG, Chow EWC, Little D, Hogan J, Hodgkinson K, Bassett AS. Linkage of Familial Schizophrenia to Chromosome 13q32. American Journal of Human Genetics 1999; 65:1096-1103. PMCID:PMC1288243

11. Gharani N, Benayed R, Mancuso, V, Brzustowicz LM, Millonig JH. Association of the Homeobox Transcription Factor, ENGRAILED 2, with Autism Spectrum Disorder. Molecular Psychiatry 2004; 9:474-484.

12. Widom C, Brzustowicz LM. MAOA and the “Cycle of Violence”: Childhood Abuse and Neglect, MAOA Genotype, and Risk for Violent and Antisocial Behavior. Biological Psychiatry, 2006;60:684-689.

13. Bruse S, Moreau MP, Azaro MA, Zimmerman RP, Hoffman A, Brzustowicz LM: Improvements to Bead Based Oligonucleotide Ligation SNP Genotyping Assays. Biotechniques, 2008; 45:559-571. NIHMSID182125

14. Benayed R, Choi J, Matteson PG, Gharani N, Kamdar S, Brzustowicz LM, Millonig JH. Autism Associated Haplotype Affects the Regulation of the Homeobox Gene, ENGRAILED 2. Biological Psychiatry, 2009;66:911-917. PMCID:PMC2783416

15. Bassett AS, Scherer SW, Brzustowicz LM. Copy Number Variations in Schizophrenia: Critical Review and New Perspectives on Concepts of Genetics and Disease. American Journal of Psychiatry, in press.

Active Grants (as Principal Investigator): • NIH – NIMH, RC1 MH088288

Behavioral and Genetic Biomarker Development for Autism and Related Disorders 9/30/09 – 8/31/11: $993,675 total direct costs

• NIH – NIMH, R01 MH080429 Elucidating the Role of miRNA Dysregulation in Schizophrenia and Bipolar Disorder 4/1/07 – 3/31/12: $2,748,613 total direct costs

• NIH – NIMH, R01 MH076435 Identification and Functional Assessment of Autism Susceptibility Genes 9/30/05 – 7/31/10: $1,652,474 total direct costs

• NARSAD Staglin Family Music Festival Schizophrenia Research Award 7/1/05 – 6/30/10, $230,000 total directcosts • Autism Speaks, Mentor-Based Postdoctoral Fellowship

Genetic Studies of Autism Susceptibility 2/1/08 – 3/31/10, $100,476 total direct costs Active Grants (as Co-Investigator): • NIH – NIMH, R01 MH86117 (Vieland)

Combining Epidemiologic Designs to Model Genetic Risks for Psychiatric Disorders 6/5/09 – 5/31/11: $2,393,264 total direct costs ($696,370 for Brzustowicz subcontract)

• NIH - NIMH, U24 MH068457 (Tischfield) NIMH Center for Collaborative Genetic Studies on Mental Disorders 9/23/08 – 5/31/13: $28,780,925 total direct costs

Completed Grants (as Principal Investigator): • NIH - NIMH, R01 MH62440

Molecular Genetics of Schizophrenia Susceptibility 2/01/04 - 1/31/09: $1,666,330 total direct costs

• NIH - NIMH, R01 MH70366 Genetic Components of Autism Spectrum Disorders 9/29/03 - 6/30/08 (NCE to 6/30/09): $3,064,398 total direct costs

• New Jersey Governor’s Council on Autism Genetic Analysis of an Autism Susceptibility Locus on Chromosome 1q23-25 7/1/05 – 6/30/08, $189,380 total direct costs • March of Dimes Research Award, 12-FY02-107

Genetic Studies of Language and Reading Impairment in Canadian Families 6/1/02 - 9/30/07: $255,239 total direct costs

Completed Grants (as Co-Investigator): • NIH - NIMH, U24 MH068457 (Tischfield)

NIMH Center for Collaborative Genetic Studies on Mental Disorders 7/1/03 - 06/30/08: $14,654,462 total direct costs

BIOGRAPHICAL SKETCH

NAME George M. Carman eRA COMMONS USER NAME Carman

POSITION TITLE Professor II



William Paterson College, Wayne, NJ B.A. 1972 Biology Seton Hall University, So. Orange, NJ M.S. 1974 Microbiology University of Massachusetts, Amherst, MA Ph.D. 1977 Biochemistry University of Texas Medical School, Houston Postdoc 1977-78 Biochemistry/Mol. Biol.

A. Personal Statement Dr. Carman’s research utilizes molecular genetic and biochemical approaches to study the regulation of phospholipid metabolism in the yeast Saccharomyces cerevisiae. Phospholipids are essential molecules that contribute to the structural definition of cell membranes, and participate in the regulation of cellular processes as signaling molecules and as reservoirs of lipid messengers. The Carman laboratory has made significant contributions to the understanding of phospholipid synthesis in yeast through the purification and characterization of several enzymes and the isolation and characterization of key genes. The laboratory has played a major role in the discovery that the expression of phospholipid biosynthetic enzymes is regulated by phospholipid precursors and the mineral zinc; and that key enzymes are regulated by membrane- and cytosolic-associated components and by covalent modification by protein kinases. These forms of enzyme regulation have profound effects on membrane phospholipid composition and have important medical implications for understanding the molecular basis for various diseases. His work is currently funded by two NIH grants, one of which examines the phosphorylation and regulation of phosphatidate phosphatase, a major fat-regulating enzyme important to diseases such as obesity, diabetes, and heart disease. He collaborates with Dr. Li to identify major sites of enzyme phosphorylation. B. Positions and Honors Appointments

Assistant Professor, Department of Food Science, Rutgers University (1978-1982) Associate Professor, Department of Food Science, Rutgers University (1982-1986) Professor I, Department of Food Science, Rutgers University (1986-1990) Visiting Fellow, Department of Molecular Biology, Princeton University (1990-1991) Professor II, Department of Food Science, Rutgers University (1990-present) Director, Rutgers Center for Lipid Research (2007-present)

Professional Activities and Honors

Advisory Panels: NIH Study Section Boundaries Team (for Biological Chemistry and Macromolecular Biophysics Integrated Review Groups, 2003); NIH Biological Chemistry and Macromolecular Biophysics Study Section (2009, 2008, 2006); NIH Physiological Chemistry Study Section (1998-2002, 1988-1992); NIH Reviewers Reserve (1992-1996); NIH Chemistry and Related Sciences Special Emphasis Panel (1998, 2004); NSF Panel for Research Experiences for Undergraduates (1987); Biotechnology and Biological Sciences Research Council of Scotland, Visiting Committee (1999).

Editorial Boards: Journal of Biological Chemistry, Associate Editor (2006-2011), Board Editor (1998-2003, 1992-1997); Analytical Biochemistry, Executive Editor (1994-2012); Journal of Lipid Research, Associate Editor (2003-2006), Board Member, 2006-2012); Biochimica et Biophysica Acta, Executive Editor (2004-2006); Journal of Bacteriology, Board Member (1992-1994); Applied and Environmental Microbiology, Board Member (1985-1990); Gene Regulation and Systems Biology, Board Member (2006-2008); Journal of Food

Biochemistry, Board Member (1979-1992); Journal of Food Science, Board Member (1985-1987); World Journal of Biological Chemistry, Board Member (2009-2013).

Professional Activities: American Society for Biochemistry and Molecular Biology (ASBMB) Meetings Committee Chair (2002-2004); ASBMB Annual Meeting Program Committee Co-Chair (2001, 2006) and Member (1998); ASBMB Satellite Meeting “Membranes Lipids and Cell Function” Co-Organizer (2001); ASBMB Satellite Meeting “Molecular Characterization of Membrane Lipid Metabolism” Co-Organizer (1998); Keystone Symposium “Cell Activation and Signal Transduction: Lipid Second Messengers IV” Organizer (2000); Gordon Research Conference “Lipid Metabolism” Chair (1993).

Honors: American Oil Chemists Society-Supelco/Nicholas Pelick Research Award (2004); Research Excellence Award for Sustained Research and Impact, School of Environmental and Biological Sciences, Rutgers University, 2009; Faculty Mentor of the Year, Compact for Faculty Diversity, 2008; Endel Karmas Teaching Award (2004); Rutgers University Board of Trustees Award for Excellence in Research (1999); American Academy of Microbiology Fellow (1998); Foundation for Microbiology Lecturer (1996-1998); Selman A. Waksman Honorary Lectureship Award (1996); NJ Agricultural Research Experiment Station Research Excellence Award (1993); Distinguished Alumni Award, William Paterson College (1981); Welch Foundation Postdoctoral Fellowship (1977); Manufacturers Hanover Trust Co. Scholarship (1968). C. Peer-reviewed Publications (selected from a total of 160) Choi, M.-G., V. Kurnov, M.C. Kersting, A. Sreenivas, and G.M. Carman. 2005. Phosphorylation of the yeast choline kinase by protein kinase C. Identification of Ser25 and Ser30 as major sites of phosphorylation. J. Biol. Chem. 280: 26105-26112. (PMCID: PMC1383591) Han, G.-S., A. Sreenivas, M.-G. Choi, Y.-F. Chang, S.S. Martin, E.P. Baldwin, and G.M. Carman. 2005. Expression of human CTP synthetase in Saccharomyces cerevisiae reveals phosphorylation by protein kinase A. J. Biol. Chem. 280: 38328-38336. (PMCID: PMC1400552) Chang, Y.-F., and G.M. Carman. 2006. Casein kinase II phosphorylation of the yeast phospholipid synthesis transcription factor Opi1p. J. Biol. Chem. 281: 4754-4761. (PMCID: PMC1978165) O’Hara, L., G.-S. Han, S. Peak-Chew, N. Grimsey, G.M. Carman, and S. Siniossoglou. 2006. Control of phospholipid synthesis by phosphorylation of the yeast lipin Pah1p/Smp2p Mg2+-dependent phosphatidate phosphatase. J. Biol. Chem. 281: 34537-34548. (PMID: 16968695) Choi, M.-G., and G.M. Carman. 2007. Phosphorylation of human CTP synthetase 1 by protein kinase A. Identification of Thr455 as a major site of phosphorylation. J. Biol. Chem. 282: 5367-5377. (PMCID: PMC2014738) Chang, Y.-F., S.S. Martin, E.P. Baldwin, and G.M. Carman. 2007. Phosphorylation of human CTP synthetase 1 by protein kinase C. Identification of Ser462 and Thr455 as major sites of phosphorylation. J. Biol. Chem. 282: 17613-17622. (PMCID: PMC2081159) Han, G.-S., S. Siniossoglou, and G.M. Carman. 2007. The cellular functions of the yeast lipin homolog Pah1p are dependent on its phosphatidate phosphatase activity. J. Biol. Chem. 282: 37026-37035. (PMID: 17971454) Soto, A., and G.M. Carman. 2008. Regulation of the Saccharomyces cerevisiae CKI1-encoded choline kinase by zinc depletion. J. Biol. Chem. 283: 10079-10088. (PMID: 18276583) Han, G.-S., L. O’ Hara, G.M. Carman, and S. Siniossoglou. 2008. An unconventional diacylglycerol kinase that regulates phospholipid synthesis and nuclear membrane growth. J. Biol. Chem. 283: 20433-20442. (PMID: 18458075)

Han, G.-S., L. O’ Hara, S. Siniossoglou, and G.M. Carman. 2008. Characterization of the yeast DGK1-encoded CTP-dependent diacylglycerol kinase. J. Biol. Chem. 283: 20443-20453. (PMID: 18458076) Nadra, K., A.-S. de Preux Charles, J.-J. Médard, W.T. Hendriks, G.-S. Han, S. Grès, G.M. Carman, J.-S. Saulnier-Blache, M.H.G. Verheijen, and R. Chrast. 2008. Phosphatidic acid mediates demyelination in Lpin1 mutant mice. Genes Dev. 22, 1647-1661. (PMID: 18559480) Grimsey, N., G. S. Han, L. O’ Hara, J. J. Rochford, G. M. Carman, and S. Siniossoglou. 2008. Temporal and spatial regulation of the phosphatidate phosphatases lipin 1 and 2. J. Biol. Chem. 283: 29166-29174. (PMID: 18694939) Carman, G.M., and G.-S. Han. 2009. Phosphatidic acid phosphatase, a key enzyme in the regulation of lipid synthesis. J. Biol. Chem. 284: 2593-2597. (PMID: 18812320) Carman, G.M., and G.-S. Han. 2009. Regulation of phospholipid synthesis in yeast. J. Lipid Res. 50: S69-S73. (PMID: 18955729) Choi, H.-S., G.-S. Han, and G.M. Carman. 2010. Phosphorylation of yeast phosphatidylserine synthase by protein kinase A. Identification of Ser46 and Ser47 as major sites of phosphorylation. J. Biol. Chem. Feb 9. [Epub ahead of print] (PMID: 20145252) D. Research Support (Ongoing)

R01 GM-50679 (years 16-19), NIH/NIGMS, Period: 5/1/09 to 4/30/13 Regulation of Phospholipid Synthesis This grant examines the regulation of phosphatidate phosphatase by phosphorylation. Principal Investigator: George M. Carman R01 GM-28140 plus ARRA supplement (years 24-27), NIH/NIGMS, Period: 7/1/06 to 06/30/10 Phospholipid Metabolism and Membrane Function This grant examines the role of phosphatidate phosphatase and zinc in phospholipid synthesis regulation. Principal Investigator: George M. Carman

Principal Investigator/Program Director (Last, First, Middle): Carman, George M.

PHS 398/2590 (Rev. 05/01)

OTHER SUPPORT Carman, G.M. ACTIVE

GM 28140-27 NIH/NIGMS Phospholipid Metabolism and Membrane Function

07/01/06-06/30/10 $239,837 (direct cost)

3.0 Calendar

The major goals of this project are to examine the regulation of phosphatidate phosphatase by zinc depletion, examine the transcriptional regulation of phospholipid synthesis genes by zinc, and examine regulation of zinc transport by phospholipid composition. OVERLAP There is no scientific or budgetary overlap with GM 50679. GM 28140-27 ARRA Administrative Supplement NIH/NIGMS Phospholipid Metabolism and Membrane Function

07/01/09-06/30/10 $76,500 (direct cost)

3.0 Calendar

This supplement was used to purchase of a GE Healthcare Storm 865 instrument for filmless autoradiography, fluorescence, and chemifluorescence imaging. OVERLAP USE This instrument is being used for routine biochemical and molecular experiments performed under both GM 28140 and GM 50679. GM 50679-16 NIH/NIGMS Regulation of Phospholipid Synthesis

05/01/09-04/30/13 $212,500 (direct cost)

3.0 Calendar

The major goals of this project are to examine multiple phosphorylations of phosphatidate phosphatase by protein kinases (e.g., cyclin-dependent kinase, protein kinases A and C), and to examine the effects of the phosphorylations on phosphatidate phosphatase activity and its cellular location, and physiological relevance. OVERLAP There is no scientific or budgetary overlap with GM 28140. Carman, G.M. PENDING

GM 28140-28 NIH/NIGMS Phospholipid Metabolism and Membrane Function

07/01/10-06/30/14 $250,000 (direct cost)

3.0 Calendar

The major goals of this project are to examine the regulated expression of yeast PAH1-encoded phosphatidate phosphatase during growth, examine the biochemical regulation of human phosphatidate phosphatase isoforms, and to examine the regulation of yeast DGK1-encoded diacylglycerol kinase during growth. OVERLAP There is no scientific or budgetary overlap with GM 50679.



NAME Chada, Kiran eRA COMMONS USER NAME Chada04

POSITION TITLE Professor of Biochemistry



Oxford University, Oxford, England B.A. 1978 Biochemistry Oxford University, Oxford, England D. Phil 1983 Dev. Biology Columbia University, New York, NY Postdoc. 1986 Dev. Biology

A. Positions and Honors. Positions and Employment 1986-1992 Assistant Professor, Dept. of Biochem., UMDNJ-RWJMS, Piscataway, NJ 1992-1997 Associate Professor, Dept. of Biochem., UMDNJ-RWJMS, Piscataway, NJ 1997- Professor, Department of Biochemistry, UMDNJ-RWJMS, Piscataway, NJ 1999- Director, Genomics Center of New Jersey, Piscataway, NJ Other Experience and Professional Memberships 1984 Asst. Instructor, Molecular Embryology of the Mouse Cold Spring Harbor Lab. 1990-1994 Member of Developmental Biology Study Section (NSF) 1993 Member of USAMRDC Breast Cancer Program Peer Review 1994-1997 Member of NIH HED Study Section 2002- Editorial Board Member of Journal of Clinical Investigation 2003-2007 NIH Biomedical Research and Research Training Study Section Honors and Awards 1983-1985 NATO Postdoctoral Fellowship 1987-1990 Basil O’Connor Starter Scholar 1990 University Excellence Award For Distinguished Biomedical Research 1993 University Excellence Award For Distinguished Biomedical Research

B. Selected peer-reviewed publications (in chronological order). (Publications selected from 60 peer-reviewed publications) 1. Chada, K., Magram, J., Radice, G., Lacy, E., Costantini, F. Specific expression of a foreign globin gene

in erythroid cells of transgenic mice. Nature 1985; 314: 377-380. 2. Magram, J., Chada, K., Costantini, F. Developmental regulation of a cloned adult beta-globin gene in

transgenic mice. Nature 1985; 315: 338-340. 3. Chada, K., Magram, J., Costantini, F. An embryonic pattern of expression of a human fetal globin gene

in transgenic mice. Nature 1986; 319: 685-689. 4. Costantini, F., Chada, K., Magram, J. Correction of murine beta-thalassemia by gene transfer into the

germline. Science 1986; 233: 1192-1194. 5. Xiang, X., Benson, K.F., Chada, K. Mini-mouse: Disruption of the pygmy locus in a transgenic

insertional mutant. Science 1990; 247: 967-969.

6. Pellas, T.C., Ramachandran, B., Duncan, M., Pan, S.S., Marone, M., Chada, K. Germ cell deficient, (gcd), a novel insertional mutation manifested as infertility in transgenic mice. Proc. Natl. Acad. Sci. USA 1991; 88: 8787-8791.

7. D’Armiento, J., Dalal, S., Okada, Y., Berg, R. Chada, K. Collagenase expression in the lungs of transgenic mice causes pulmonary emphysema. Cell 1992; 71: 955-961.

8. Benson, K., Chada, K. Mini-Mouse: Phenotypic characterization of a transgenic insertional mutant allelic to pygmy. Genetical Res. 1994; 64: 27-33. 9. Meng, X., Benson, K., Chada, K., Huff, E.J., Schwartz, D.C. Optical mapping of lambda clones using

restriction endonucleases. Nature Genetics 1995; 9: 432-439. 10. Ashar, H.R., Schoenberg Fejzo, M., Tkachenko, A., Zhou, X., Fletcher, S., Weremowicz, S., Morton,

C.C., Chada, K. Disruption of HMGI-C: DNA-binding motifs fused in lipomas to distinct transcriptional regulatory domains. Cell 1995; 82: 57-65.

11. Zhou, X., Benson, K., Ashar, H., Chada, K. Mutation responsible for the mouse pygmy phenotype in developmentally regulated factor HMGI-C. Nature 1995; 376: 771-774.

12. D'Armiento, J., DiColandrea, T., Dalal, S., Okada, Y., Huang, M-T, Conney, A., Chada, K. Collagenase expression in transgenic mouse skin causes hyperkeratosis and acanthosis and susceptibility to tumorigenesis. Mol. Cell. Biol. 1995; 15: 5732-5739.

13. Tkachenko, A., Ashar, H., Sandberg, A., Chada, K. Misexpression of disrupted HMGI factor activates alternative tumorigenesis pathways. Cancer Res. 1997; 57: 2276-2280.

14. Anand, A., Chada, K. In vivo modulation of Hmgi-c reduces obesity. Nature Genetics 2000; 24: 377-380.

15. Liu, J., Schiltz, J., Shah, P., Chada, K. Genomic structure and expression of the murine HMGI(Y) gene. Gene 2000; 246: 197-207. 16. DiColandrea, T., D’Armiento, J. and Chada, K. Collagenase induction precedes tumorigenesis in mice. Mol. Carcinogenesis, 2000; 29: 8-16. 17. Schiltz, J., Kesari, K., Ashar, H., Chada, K. Hmgi-c independent activation of MuRantes In vivo. Cell,

Growth, and Differentiation 2002; 13: 39-45. 18. Benson, K., Chada, K. Molecular characterization of mouse In(10)17Rk inversion and identification of a

novel muscle gene at the breakpoint. Genetics 2002; 160: 279-287. 19. Agoulnik, A.I., Lu, B., Zhu, Q., Truong, C., Arango, N., Chada, K.K., Bishop, C.E. A novel gene, Pog, is

necessary for primordial germ cell proliferation in the mouse and underlies the germ cell deficient mutation, gcd. Hum. Mol. Genet. 2002; 11: 3047-3053.

20. Ashar, H.R., Tkachenko, A., Shah, P., Chada, K. HMGA2 is expressed in an allele-specific manner in lipomas. Cancer Genet. and Cytogenet. 2003; 143: 160-168.

21. Liu, J. Schiltz, J.F. Ashar, H.R., Chada, K. Hmga1 is required for normal sperm development. Mol. Reprod. and Dev. 2003; 66: 81-89.

22. Schiltz, J.F., Rustighi, A., Tessari, M.A., Liu, J., Braghetta, P., Sgarra, R., Stebel, M., Bressan, G.M., Altruda, F., Giancotti, V., Chada, K., Manfioletti, G. Hmga2 promoter analysis in transgenic mice. Biochem. Biophys. Research Commun. 2003; 309: 718-723.

23. Miyazawa J, Mitoro A, Kawashiri S, Chada K, Imai K. Expression of mesenchyme specific HMGA2 in squamous carcinomas of the oral cavity. Cancer Res. 2004; 64: 2024-2029.

24. Brants, J.R., Ayoubi, T.A.Y., Chada, K., Van de Ven, W.J.M., Petit, M.M.R. Differential regulation of the insulin-like growth factor II mRNA-binding protein genes by architectural transcription factor HMGA2. FEBS Letters 2004; 569: 277-283. 25. Imai, K., Chada, K. Ectopic activation of mesenchyme-specific genes induce the epithelial- mesenchymal transition in oral cancer. Res. Adv. In Cancer 2005; 5: 41-47. 26. Sato, K., Ueda, Y., Shimasaki, M., Ozaki, M., Nitta, N., Chada, K., Ishikawa, Y. and Katsuda, S. (2005). Pleomorphic adenoma (benign mixed tumor) of the breast: A case report and review of the literature. Pathol. Res. Pract., 201, 333-339. 27. Zaidi, R., Okada, Y., Chada, K. Misexpression of full-length HMGA2 induces benign mesenchymal tumors in mice. Cancer Res. 2006; 66: 7453-7459. 28. Hu, R., Khor, T., Shen, G., Jeong, W., Hebbar, V., Chen, C., Xu, C., Reddy, B., Chada, K., Kong, T. Cancer chemoprevention of intestinal polyposis in ApcMin/+ mice by sulforaphane, a natural product derived from cruciferous vegetable. Carcinogenesis. 2006; 27: 2038-2046.

29. Khor, T., Hu, R., Shen, G., Jeong, W., Hebbar, V., Chen, C., Xu, C., Nair, S., Reddy, B., Chada, K. and Kong, T. (2006). Pharmacogenomics of cancer chemopreventive isothiocyanate compound sulforaphane in the intestinal polyps of ApcMin/+ mice. Biopharm. Drug Dispos., 27, 407-20. 30. D'Armiento, J., Imai, K., Schiltz, J., Kolesnekova, N., Sternberg, D., Benson, K., Pardo, A., Selman, M., Smolarek, T., Vundavalli M, Sonnet J, Szabolcs M., Chada, K. Identification of the benign mesenchymal tumor gene HMGA2 in lymphangiomyomatosis. Cancer Res. 2007; 67: 1902-1909

31. Rosenzweig, E., Morse, J, Knowles, J, Chada, K., Khan, A., Roberts, K., McElroy, J., Juskiw, N., Mallory, N., Rich, M., Diamond, B. and Barst R. (2008). Clinical implications of determining BMPR2 mutation status in a large cohort of children and adults with pulmonary arterial hypertension. J. Heart Lung Transplant., 27, 668-674.

32. Nishino, J., Kim, I., Chada, K. and Morrison, S. (2008). Hmga2 promotes neural stem cell self-renewal in young but not old mice by reducing p16Ink4a and p19Arf expression. Cell, 135, 227-239. 33. Ashar H., Chouinard R., Jr, Dokur M. and Chada, K. (2010). In vivo modulation of HMGA2 expression. Biochem. Biophys. Acta 1799, 55-61.

C. Research Support. Ongoing Research Support 854632 Chada (PI) 06/01/08-05/31/10 Centre for Rare Lung Disorders, Columbia University The Mechanism of HMGA2 in Pulmonary Lymphangiomyomatosis This is a pilot study to identify the HMGA2 downstream target genes in mesenchymal tumors. Role: Principal Investigator Completed Research Support W81XWH-05-1-0184 Chada (PI) 01/1/05-12/31/07 Department of Defense HMGA2 and Tuberous Sclerosis The goal of this study is to define the role of HMGA2 in the tumorigenic pathway in tuberous sclerosis tumors. Role: Principal Investigator 506987 Chada (PI) 08/01/06-12/31/07 New Jersey Commission on Science and Technology Screen for Inhibitor of Obesity Target This proposal is concerned with assay development for an adipocyte-specific gene. Role: Principal Investigator W81XWH-04-1-0694 Chada (PI) 07/15/04-07/14/05 Department of Defense HMGA2 and Cyclin A in the Progression of Breast Cancer This proposal was concerned with the interaction of HMGA2 and the cell cycle in cancer Role: Principal Investigator 645271 Chada (PI) 03/01/02-02/28/05 New Jersey Commission on Science and Technology HMGA2 in Cancer and Obesity This proposal is concerned with the utilization of the various HMGA2 mouse models in cancer and obesity. Role: Principal Investigator RO1 CA77929 Chada (PI) 06/01/98-05/31/04 National Institutes of Health HMGI Genes in Tumorigenesis This proposal is concerned with the function of the HMGA2 genes in mesenchymal tumorigenesis.

Role: Principal Investigator



NAME Chen, Kevin Christopher eRA COMMONS USER NAME (credential, e.g., agency login) kc1111.nyu

POSITION TITLE Assistant Professor of Genetics and Quantitative Biology



Princeton University A.B. 05/00 Computer Science University of California, Berkeley M.S. 05/03 Computer Science University of California, Berkeley Ph.D. 12/05 Computer Science New York University Postdoctoral 08/09 Biology

Please refer to the application instructions in order to complete sections A, B, C, and D of the Biographical Sketch. A. Personal Statement

The goal of Sergio Lukic’s proposal is to apply mathematical techniques (specifically spectral methods for numerically solving partial differential equations) that he developed in his first postdoc with Prof. Simon Donaldson to problems in biology. In particularly, he is interested in the problem of coevolution of Piwi-associated RNAs (piRNAs) and transposable elements. As can be seen from my publications, I have extensive experience in the field of small RNA evolution, particularly animal microRNAs. In addition, I have a manuscript on miRNA star targeting in vertebrates in preparation with the Adam Siepel (Cornell) and Eric Lai (MSK). I also have experience applying population genomics methods to transcription factor binding sites in yeast, and I have a manuscript in preparation on these results with Mark Siegal (NYU) and Erik van Nimwegen (Biozentrum, Basel). Sergio’s mathematical techniques are highly complementary to my own expertise, which are in bioinformatics and combinatorial algorithms. I believe that I am qualified to further his education in computer science and biology, and that I possess the mathematical knowledge to guide his theoretical work. Finally I will work with other members of the Rutgers faculty to provide Sergio with solid mentorship, particularly Jody Hey and Anirvan Sengupta. B. Positions and Honors Positions and Employment 2006-2009 Postdoctoral Fellow, Department of Biology, New York University 2009- Assistant Professor, Department of Genetics and BioMaPS Institute for Quantitative Biology, Rutgers University Other Experience and Professional Memberships 2008 NSF Grant Review Panel member (Advances in Biological Informatics) 2010 NSF Grant Review Panel member (Genes and Genome Systems) Honors 2000 AT&T Research Competition (Masters Division) Declined UC Berkeley MICRO Fellowship

Declined National Science Foundation Graduate Fellowship 2000-2003 National Defense Science and Engineering Graduate Fellowship 2007-2008 NIH Ruth Kirschstein Postdoctoral Fellowship 2008-2012 NIH Pathway to Independence Award C. Peer-reviewed Publications Most-relevant to the current application

1. K. Chen, J. Maaskola, M. L. Siegal and N. Rajewsky. Reexamining microRNA site accessibility in Drosophila: a population genomics study. PLoS ONE 4(5):e5681, 2009.

2. K. Chen and N. Rajewsky. The evolution of gene regulation by transcription factors and microRNAs. Nature Reviews Genetics 8:93-103, 2007.

3. K. Chen and N. Rajewsky. Deep conservation of microRNA-target relationships and 3' UTR motifs in vertebrates, flies and nematodes. Cold Spring Harbor Symposia on Quantitative Biology, Vol. 71, Regulatory RNAs, 2007.

4. K. Chen and N. Rajewsky. Natural selection on human microRNA binding sites inferred from SNP data . Nature Genetics 38:1452-1456, 2006.

5. S. Lall, D. Grun, A. Krek, K. Chen, Y. Wang et al. A genome-wide map of conserved microRNA targets in C. elegans . Current Biology 16(5):460-471, 2006

Additional publications

1. S. E. Celniker, et al. Unlocking the secrets of the genome. Nature. 2009 Jun 18;459(7249):927-30 2. K. Chaudhuri, K. Chen, R. Mihaescu and S. Rao. On the tandem duplication-random loss model of

genome rearrangement. SODA 2006. 3. A. Bachrach, K. Chen, C. Harrelson, R. Mihaescu, S. Rao and A. Shah. Lower Bounds for Maximum

Parsimony with Gene Order Data. RECOMB Comparative Genomics, 2005 4. K. Chen and L. Pachter. Bioinformatics for Whole-Genome Shotgun Sequencing of Microbial

Communities. PLoS Computational Biology 1(2):e24, 2005 5. S. Tringe, C. von Mering, A. Kobayashi, A. Salamov, K. Chen, et al. Comparative Metagenomics of

Microbial Communities. Science 308(5721):554-557, 2005. 6. M. Charikar, K. Chen and M. Farach-Colton. Finding Frequent Items in Data Streams. Theoretical

Comp. Sci., 312(1):3-15, 2004 (Preliminary version in ICALP 2002) 7. K. Chen, D. Durand and M. Farach-Colton. Notung: A Program for Dating Gene Duplications and

Optimizing Gene Family Trees. Journal of Computational Biology, 7(3/4):429-447, 2000. (Preliminary version in RECOMB 2000 Notung: Dating Gene Duplications Using Gene Family Trees.)

8. K. Chen and V. Ramachandran. A Space-Efficient Randomized DNA Algorithm for k-SAT. 6th International Meeting on DNA Based Computers, 2000.

9. K. Chen and E. Winfree. Error-Correction in DNA Computing: Misclassification and Strand Loss. DNA Computers V, American Mathematical Society, 2000, pp 49-63

Note: In computer science, authors are listed alphabetically. In biology, authors are listed according to their contribution to the paper.

D. Research Support R00 HG Chen (PI) 09/01/09 – 08/31/12 Genome-wide identification of cis-regulatory polymorphism in S. cerevisiae Role: PI

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0005681

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0005681

http://www.nature.com/nrg/journal/v8/n2/full/nrg1990.html

http://www.cshl-symposium.org/doi/abs/10.1101/sqb.2006.71.039?cookieSet=1&journalCode=sqb

http://www.cshl-symposium.org/doi/abs/10.1101/sqb.2006.71.039?cookieSet=1&journalCode=sqb

http://www.nature.com/ng/journal/v38/n12/full/ng1910.html

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6VRT-4J5TJ06-1&_coverDate=03%2F07%2F2006&_alid=459063603&_rdoc=1&_fmt=&_orig=search&_qd=1&_cdi=6243&_sort=d&view=c&_acct=C000000333&_version=1&_urlVersion=0&_userid=30681&md5=546fa3aa209005861cbeeea8de293608

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6VRT-4J5TJ06-1&_coverDate=03%2F07%2F2006&_alid=459063603&_rdoc=1&_fmt=&_orig=search&_qd=1&_cdi=6243&_sort=d&view=c&_acct=C000000333&_version=1&_urlVersion=0&_userid=30681&md5=546fa3aa209005861cbeeea8de293608

http://genfaculty.rutgers.edu/uploads/25/kchaudhuri.pdf

http://genfaculty.rutgers.edu/uploads/25/kchaudhuri.pdf

http://genfaculty.rutgers.edu/uploads/25/recombcg_final.pdf

http://genfaculty.rutgers.edu/uploads/25/recombcg_final.pdf

http://compbiol.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pcbi.0010024

http://compbiol.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pcbi.0010024

http://www.sciencemag.org/cgi/content/full/308/5721/554

http://www.sciencemag.org/cgi/content/full/308/5721/554

http://homepages.nyu.edu/%7Ekc1111/frequent_items.ps

http://genfaculty.rutgers.edu/uploads/25/notung%281%29.pdf

http://genfaculty.rutgers.edu/uploads/25/notung%281%29.pdf

http://homepages.nyu.edu/%7Ekc1111/dna_ksat.ps

http://homepages.nyu.edu/%7Ekc1111/error_correction.ps



NAME Suzie Chen eRA COMMONS USER NAME (credential, e.g., agency login) suziec




Trinity College, Hartford, CT B.S. 05/73 Mathematics Albert Einstein College of Medicine, Bronx, NY M.S. 10/76 Genetics Albert Einstein College of Medicine, Bronx, NY Ph.D. 10/79 Genetics Columbia University, New York, NY Postdoctoral 10/79-06/83 Cell Biology/Virology

A. Personal Statement The goals of this project are to investigate the requirement of expression of metabotropic glutamate receptor 1 (GRM1) in the onset and maintenance of transformation in human melanocytes in vitro and in vivo. In parallel, we will also explore the underlying mechanisms of aberrant expression of GRM1 in human melanomas. I have the background and expertise to successfully carry out the in vivo animal model experiments proposed in the current application. As a graduate student at Albert Einstein College of Medicine, my graduate research was focused on the development of spontaneous lymphoma in the progeny of two inbred strains of mice with no known predisposition to lymphoma. We had demonstrated that the onset of spontaneous T-cell lymphoma in the progeny was a result of genetic complementation. Subsequent to attaining my Ph.D. in Genetics I carried out my postdoctoral training at Columbia University where I began work on cell transformation and DNA tumor virus, SV40. We identified a specific rearranged form of SV40 which was always detected only in cells which were also have acquired the anchorage-independence growth characteristics. While at Columbia University, I became interested in the regulation of cell differentiation and I adopted an adipocyte differentiation system developed by Dr. H. Green as our model. Through utilizing molecular cloning techniques and functional assays we identified two small fragments of genomic DNA each one has the ability to induce adipocyte differentiation when introduced into a variety of fibroblasts. I took this project with me when I begun my independent position at Rutgers University. I expanded the studies in whole animals by making transgenics with cloned DNA fragments. One out of five founder mice developed spontaneous melanoma due to “insertional mutagenesis”. We identified and confirmed that ectopic expression of GRM1 in melanocytes is sufficient to induce spontaneous melanoma development in vivo. We also demonstrated that about 60% of human melanoma cell lines and biopsies showed aberrant GRM1 expression. Using an FDA approved drug that inhibits the release of glutamate, a natural ligand for GRM1 led to a decrease in the number of viable melanoma cells in vitro and in vivo. These laboratory-based findings were translated to the clinic in a Phase 0 Clinical Trial in collaboration with Dr. J. Goydos at the Cancer Institute of NJ. This Phase 0 trial was supported by an R21 grant from NCI and results from this completed trial were published in Clinical Cancer Research. We just opened a Phase 2 Clinical Trial also supported by an R21 grant. In summary, I have a strong track record in studies of mechanisms in cellular transformation in vitro and in vivo. I have the knowledge and expertise to successfully accomplish the pre-clinical studies in this application. I also have demonstrated my ability to translate laboratory findings to the clinic. B. Positions and Honors Positions and Employment 1976-1979 Pre-doctoral Study at Albert Einstein College of Medicine, with Dr. Frank Lilly, Bronx, NY 1979-1983 Postdoctoral Fellow, Biological Sciences, Columbia University, with Dr. Robert Pollack,

New York, NY 1984-1986 Research Scientist, Biological Sciences, Columbia University, New York, NY 1986-1991 Associate Research Scientist, Biological Sciences, Columbia University, New York, NY

1991-1992 Senior Research Scientist, Biological Sciences, Columbia University, New York, NY 1992-1998 Assistant Professor, College of Pharmacy, Rutgers University, Piscataway, NJ 1998-2005 Associate Professor, College of Pharmacy, Rutgers University, Piscataway, NJ 2005-Present Professor, College of Pharmacy, Rutgers University, Piscataway, NJ Other Experience and Professional Memberships 1988-1989 NCI Virology Study Section, ad hoc 2003 Feb NCI Metabolic Pathology Study Section, ad hoc 2003 Oct NCI Tumor Cell Biology Study Section, ad hoc 2004 Mar NCI Special Emphasis Panel, ad hoc 2004 Jun NCI Program Project Parent Subcommittee C, ad hoc 2004 Jun NCI Cancer Genetics Study Section, ad hoc 2004 Dec NCI Special Emphasis Panel, ad hoc 2004-2008 NCI Tumor Cell Biology Study Section, chartered member 2005 March NCI Special Emphasis Panel, ad hoc 2005 April NCI Special Emphasis Panel, ad hoc 2006 April NCI Special Emphasis Panel, ad hoc 2007 Oct NCI Special Emphasis Panel, ad hoc 2008 Feb NCI Special Emphasis Panel, ad hoc 2008 Oct NCI Special Emphasis Panel, ad hoc 2009 Jan NCI Molecular Oncogenesis Study Section, ad hoc 2009 Feb NCI Special Emphasis Panel, ad hoc 2009 Oct NCI Molecular Oncogenesis Study Section, ad hoc 2010 Feb NCI Tumor Cell Biology Study Section, ad hoc Honors 2005 May Keynote Speaker at Brain Tumor Center Seminar Series MD Anderson Cancer Center, Houston TX 2005 May Rutgers University Board of Trustees Award for Excellence in Research, Piscataway, NJ 2007 Nov Second International Melanoma Congress Best Abstract Award, New York, NY C. Selected Peer-reviewed Publications (Selected from over 60 peer-reviewed publications) Most relevant to the current application 1. Chen, S., Zhu, H., Wetzel, W.J. And Philbert, M.A. (1996) Spontaneous melanocytosis in transgenic mice.

J. Inv. Derm. 106:1145-1151. PMID 8618055 2. Pollock, P.M., Cohen-Solal, K.A., Sood, R., Namkoong, J., Martino, J.J., Koganti, A., Zhu, H., Robbins, C.,

Makalowska, I., Shin, S.S., Marin, Y., Roberts, K.G., Yudt, L.M., Chen, A., Cheng, J., Incao, A., Pinkett, H.W., Graham, C.L., Dunn, K., Crespo-Carbone, S.M., Mackason, K.R., Ryan, K.B., Sinsimer, D., Goydos, J., Reuhl, K.R., Eckhaus, M., Meltzer, P.S., Pavan, W.J., Trent, J.M. and Chen, S. (2003) Melanoma mouse model implicates metabotropic glutamate signaling in melanocytic neoplasia. Nat Genet. 38:108-112. PMID 12704387

3. Namkoong, J., Shin, S.S., Lee, H.J., Marín, Y.E., Wall, B.A.. Goydos, J.S. and Chen, S. (2007) Metabotropic Glutamate Receptor 1 (GRM1) and Glutamate Signaling in Human Melanoma. Cancer Res. 67:2298-2305.PMID 17332361

4. Shin, S.S., Namkoong, J., Wall, B.A., Gleason, R., Lee, H.J. and Chen, S. (2008) Oncogenic activities of metabotropic glutamate receptor 1 (Grm1) in melanocyte transformation. Pigment Cell Melanoma Res. 21:368-378. NIHMS 185787

5. Yip, D., Le, M., Chan, J., Lee, J., Mehnert, J., Yudd, A., Kempf, J., Shih, W., Chen, S. and Goydos, J. (2009) A phase 0 trial of Riluzole in patients with resectable stage III and IV melanoma. Clin. Can. Res. 15: 3896-3902. PMCID: PMC2812866

Additional recent publication of importance to the field (in chronological order) 1. Zhu, H., Reuhl, K., Zhang, X., Botha, R., Ryan, K., Wei, J. and Chen, S. (1998) Development of heritable

melanoma in transgenic mice. J. Inv. Derm., 110: 247-252. PMID 9506443 2. Zhu, H., Reuhl, K., Botha, R., Ryan, K., Wei, J. and Chen, S. (2000) Development of early melanocytic

lesions in transgenic mice predisposed to melanoma. Pigment Cell Res., 13:158-164. PMID 10885674 3. Cohen-Solal, K.A., Reuhl, K.R., Ryan, K.B., Roberts, K.G. and Chen, S. (2001) Development of cutaneous

amelanotic melanoma in the absence of a functional tyrosinase. Pigment Cell Res.14:466-474. PMID 11775059

4. Cohen-Solal, K.A., Crespo-Carbone, S.M., Namkoong, J., Mackason, K.R., Roberts, K.G., Reuhl, K.R. and Chen, S. (2002) Progressive appearance of pigmentation in amelanotic melanoma lesions. Pigment Cell Res. 15:282-289. PMID 12100494

5. Marin, Y and Chen, S. (2004) Involvement of metabotropic glutamate receptor 1, a G-protein-coupled receptor, in melanoma development. J. Mol. Med 82:735-749. PMID 15322701

6. Marin, Y., Namkoong, J., Shin, S-S, Raines, J., Degenhard, K., White, E. and Chen, S. (2005) Grm5 expression is not required for the oncogenic role of Grm1 in melanocytes. Neuropharm 49:70-79. PMID 16040064

7. Marin, Y., Namkoong, J., Cohen-Solal, K., , Shin, S. S., Martino, J., Oka, M. and Chen, S. (2006) Stimulation of Oncogenic Metabotropic Glutamate Receptor 1 in Melanoma Cells Activates ERK1/2 via PKCe. Cell Signal. 18:1279-1286. PMID 16305822

8. Marin, Y., Wang, S., Namkoong, J., Suh, J., Martino, J., Rabson, A., Yang, C.S., Chen, S. and Ryu, J.H. (2007) Curcumin downregulates the constitutive activity of NF-kappaB and induces apoptosis in novel mouse melanoma cells. Melanoma Research, 17:274-283. PMID 17885582

9. Lee, H.J., Wall, B.A. and Chen, S. (2008) G-protein-coupled receptors and melanoma. Pigment Cell Melanoma Res. 21: 415-428. NIHMS 185783

10. Shin, S. S., Wall, B. and Chen, S. (2009) AKT2 is a downstream target of metabotropic glutamate receptor 1 (mGlu1). Pig. Cell and Mel. Res. 23: 103-111. PMCID: PMC2810105

D. Research Support Ongoing Research Support RO1 CA108720 Chen (PI) 07/01/04-06/30/10, includes a one year no cost extension. Neoplastic transformation of melanocytes by Grm1 The goal of this project is to study the requirement of Grm1 in mouse melanocyte trans formation in vitro and in vivo. Role: PI Total direct cost: $967,000 RO1 CA124975 Goydos (PI) 06/01/07-05/31/12 Validation of GRM1 as a therapeutic target The goal of this project is to validate GRM1 as a therapeutic target in human melanoma. Role: CO-PI Total direct cost: $1,224,560 09-1143-CCR-EO Chen (PI) 07/01/09-06/30/10 New Jersey Commission on Cancer Research, New Jersey Cancer Research Development Award The glutamatergic pathways in melanoma The goal of this project is to assess therapeutic potential of several compounds in preclinical setting and translate to the clinics. Role: PI Total direct cost; $500,000

Program Director/Principal Investigator (Last, First, Middle): Chikindas, Michael




NAME Chikindas, Michael

POSITION TITLE Associate Professor



Yerevan State University, Yerevan, Armenia M.S. (cum laude) 1981 Microbial Genetics

Institute of Genetics and Selection of Industrial Microorganisms, Moscow, Russia Ph.D. 1987 Microbial Genetics

A. Personal Statement The goal of this study is to elucidate the mechanism of action of the natural antimicrobial peptide subtilosin A against the bacterial vaginosis-associated pathogen Gardnerella vaginalis in vitro using G. vaginalis-challenged human vaginal epithelial cells as a model system. Specifically, we plan to investigate subtilosin’s influence on the targeted cell’s proton motive force components (membrane potential and cellular pH), its ability to form pores and/or perturb the membrane, and to cause leakage/hydrolysis of cellular components like ATP. We will continue by studying subtilosin’s activity against BV-associated clinical isolates as well as its activity in combination with selected natural antimicrobials that may work synergistically with subtilosin. Finally, we will employ the accumulated knowledge to elucidate subtilosin’s activity (alone and in combination with other synergistically-acting substances) on G. vaginalis-challenged human vaginal epithelial cells, the newly established model for the prophylaxis and treatment of G. vaginalis infections. My previous training as a microbial geneticist and my professional experience with conducting research and management in academia and industry gives me the necessary skills for successful execution of the proposed study. In my professional career, I have twenty years of experience in research on lactic acid bacteria and on the genetics and mode of action of antimicrobial proteins. These studies were reported in high level peer-reviewed journals and at numerous international conferences. My current project emerges from my vast experience as a researcher with internationally-recognized expertise in antimicrobial proteins, and especially from my research of the last six years which targets vaginal microbiota and vaginal pathogens. In addition, during the last five years I gained experience in studying biofilms of human pathogens such as Salmonella and Listeria monocytogenes, which should help me in advancing G. vaginalis biofilm-related research. I have a documented record of successful accomplishments of research projects sponsored by various industries and by granting agencies such as NIH, NSF and USDA. In conclusion, I am prepared to lead the proposed project to a successful conclusion.

B. Positions and Honors

Positions and Employment 1975-1976 Laboratory Assistant. Central Laboratory, The Charentsavan Experimental Microbiological Plant "Lysine". Charentsavan, Republic of Armenia 1976-1981 Laboratory Assistant, Laboratory of Pseudomonas Genetics, Institute of Experimental Biology,

Academy of Sciences of Armenia. Yerevan, Republic of Armenia 1985-1987 Junior Researcher. All-Union Research Institute of Applied Microbiology of the Ministry of

Medical and Microbiological Industry of the USSR. Obolensk, Moscow region, Russia 1988-1990 Senior Researcher, Head of the Group. Research Center for Molecular Diagnostics of the



Ministry of Health. Moscow, Russia 1990-1993 Researcher. Department of Genetics, Center for Biological Sciences, University of

Groningen. Groningen, The Netherlands 1993-1995 Microbial Geneticist. Dental Division, Unilever Research Port Sunlight Laboratory. United

Kingdom 1995-1997 Researcher. Janssen Research Foundation. Beerse, Belgium 1997-1998 Post-Doctoral Research Fellow. Department of Biochemistry and Molecular Biology, Louisiana

State University Medical Center. Shreveport, Louisiana, USA. 1998-1999 Assistant Research Professor and an Associate Member of the Faculty (since 1999).

Department of Food Science, Rutgers University. New Brunswick, New Jersey, USA. 2000-2007 Assistant Professor. Department of Food Science, Rutgers University. 2007-present Associate Professor. Department of Food Science, Rutgers University. Other Experience and Professional Memberships 1993 – Present Reviewer for the BARD (USA - Israel) 1995 – Present External Examiner, University of Stellenbosch, South Africa 1995 – Present Reviewer for the Foundation for Research Development, South Africa 1997 – Present Member of the Editorial Board, Lett. Appl. Microbiol. and J. Appl. Microbiol. 1998 – Present Ad hoc reviewer for Journal of Food Safety, Current Biotechnology, Molecular Microbiology

and Biotechnology, Gene and Journal of Microbiological Methods 2000 – Present Ad hoc reviewer for NIH and USDA grants 2003 – Present Reviewer for the Chief Scientist of the Israeli Ministry of Agriculture Fund 2004 – Present Member of the Editorial Board, Food Microbiology 2004 – Present Member of the Editorial Board, Applied and Environmental Microbiology 2007 – Present Member of the Editorial Board, International Journal of Microbiology 2007 – Present Reviewer for the Natural Sciences and Engineering Research Council of Canada 2008 – Present Founder and Editor-in-Chief, Probiotics and Antimicrobial Proteins 2009 – Present Reviewer for the Science Foundation of Ireland (SFI) Memberships in professional societies: Society for Applied Microbiology (UK), American Society for Microbiology, Phi Tau Sigma Honorary Society, Institute of Food Technologists (IFT) - professional member. Honors 2004 Certificate of Appreciation from the Theobald Smith Society (the New Jersey Branch of the American

Society for Microbiology) for service to the Society as Local Councilor (2001-2004). 2001 Silver medal awarded by the Yerevan State University (Armenia) in recognition of achievements in

research and collaboration with international academia. 2000 1st recipient of the Young Investigator Award for the Year 2000, Theobald Smith Society, New Jersey

Branch, American Society for Microbiology. 2000 Certificate "For outstanding contributions to CAFT research conducted as a part of the Cooperative

Research Program". C. Selected Peer-reviewed Publications (from 60+ peer-reviewed publications) Most relevant to the current application 1. Y. Turovskiy, R.D. Ludescher, A.A. Aroutcheva, S. Faro and M. L. Chikindas. 2009. Lactocin 160, a

putative bacteriocin produced by vaginal Lactobacillus rhamnosus, targets cytoplasmic membranes of the vaginal pathogen, Gardnerella vaginalis. Probiotics and Antimicrobial Proteins 1: 67-74. Waiting for the NIH staff review.

2. S.E. Dover, A.A. Aroutcheva, S. Faro and M.L. Chikindas. 2008. Natural antimicrobials and their role in vaginal health: a short review. International Journal of Probiotics and Prebiotics 3: 219-230. Manuscript waiting for release to PMC.

3. K.E. Sutyak, R.A. Anderson, S.E. Dover, K.A. Feathergill, A.A. Aroutcheva, S. Faro and M.L. Chikindas. 2008. Spermicidal activity of the safe natural antimicrobial peptide subtilosin. Infectious



Diseases in Obstetrics and Gynecology Vol. 2008, Article ID 540758, 6 pages. PMID: 18923673. 4. L.E. Rosenberg, A.L. Carbone, U. Römling, K.E. Uhrich and M.L. Chikindas. 2008. Salicylic acid-

based poly(anhydride-esters) for control of biofilm formation in Salmonella enterica serovar Typhimurium. Letters in Applied Microbiology 46: 593-599. PMID: 18373656.

5. K. Sutyak, R.E. Wirawan, A.A. Aroutcheva and M.L. Chikindas. 2008. Isolation of the Bacillus subtilis antimicrobial peptide subtilosin from the dairy product-derived Bacillus amyloliquefaciens. Journal of Applied Microbiology 104: 1067-1074. PMID: 17976171.

Additional recent publications of importance to the field 1. M. Badaoui Najjar, D. Kashtanov and M.L. Chikindas. 2009. Natural antimicrobials ε-poly-L-lysine and

nisin A for control of oral microflora. Probiotics and Antimicrobial Proteins 1:143-147 2. P. Takhistov, B. George and M.L. Chikindas. 2009. Listeria monocytogenes’ step-like response to sub-

lethal concentrations of nisin. Probiotics and Antimicrobial Proteins 1:159-162. 3. M. Tabak, K. Scher, M. Chikindas and S. Yaron. 2009. The synergistic activity of triclosan and

ciprofloxacin on biofilms of Salmonella Typhimurium. FEMS Microbiology Letters 301:69-76. PMID: 19843306

4. S. Riazi, R.E. Wirawan, V. Badmaev and M.L. Chikindas. 2009. Characterization of lactosporin, a novel antimicrobial protein produced by Bacillus coagulans ATCC 7050. Journal of Applied Microbiology 106:1370-1377. PMID: 19191946.

5. S.E. Dover, A.A. Aroutcheva, S. Faro and M.L. Chikindas. 2007. Safety study of an antimicrobial peptide lactocin 160, produced by the vaginal Lactobacillus rhamnosus. Infectious Diseases in Obstetrics and Gynecology. Vol. 2007, Article ID 78248, 6 pages. PMID: 18273406.

6. C.A. Murdock, J. Cleveland McEntire, K.M. Matthews and M.L. Chikindas. 2007. The synergistic effect of nisin and lactoferrin on the inhibition of Listeria monocytogenes and Escherichia coli O157:H7. Letters in Applied Microbiology 44: 255-261. PMID: 17309501.

7. J. Li, A.A. Aroutcheva, S. Faro and M.L. Chikindas. Mode of action of lactocin 160, a bacteriocin from vaginal Lactobacillus rhamnosus 160. 2005. Infectious Diseases in Obstetrics and Gynecology 13: 135-140. PMID: 16126497.

Accepted for publication 1. N. Mazundar, M. Chikindas and K. Uhrich. 2009. Slow release polymer-iodine tablets for disinfection of

untreated surface water. Journal of Applied Polymer Science. Manuscript ID APP-2009-06-1765.R1. 2. M. Chikindas, E. Emond, A. J. Haandrikman, J. Kok, K. Leenhouts, S. Pandian, K. Venema and G.

Venema. 2009. Heterologous processing and export of the bacteriocins pediocin PA-1 and lactococcin A in Lactococcus lactis: a study with leader exchange. Probiotics and Antimicrobial Proteins. Published on-line: DOI 10.1007/s12602-009-9023-x

3. A.R. Guinta, A.L. Carbone, L.E. Rosenberg, K.E. Uhrich, M. Tabak and M.L. Chikindas. 2009. Slow release of salicylic acid from degrading poly(anhydride ester) polymer disrupts bimodal pH and prevents biofilm formation in Salmonella typhimurium MAE52 In: Biofilms: Formation, Development and Properties. Nova Science Publishers, Inc.

D. Research Support Ongoing Research Support 1R01AI084137 NIH P. Sinko (PI) 09/15/09 – 8/31/13 Multiplex nanocarrier-based hydrogels for prevention of vaginal HIV transmission, highly innovative tactics to interrupt transmission of HIV (HIT-IT). In the frames of this study, our goal is to generate a reliable epivaginal model for evaluation of hydrogels’ safety and elucidation of antimicrobial activity of novel microbicide formulations in human cells challenged with vaginal pathogens. Role: Co-PI. CRIS 0208121 USDA K. Yam (PI) 09/01/06 – 08/31/10



Development of novel food packaging for controlled release of active compounds. This project is aimed at developing a new generation of modified polymer materials which can release active compounds at predetermined rates in order to replenish active compounds for efficient control of microorganisms in the environment. Role: Co-PI. CRIS 0207508 USDA T. Montville (PI) 09/01/06 – 08/31/10 A bioenergetic approach for control of Listeria monocytogenes. This project examines how L. monocytogenes energy regulation (bioenergetics) controls its ability to grow under adverse conditions. This is demonstrated by elucidating the physiological mechanisms by which L. monocytogenes regulates its energy interconverting enzyme F0F1ATPase. This research identifies new targets for L. monocytogenes control and addresses a fundamental factor (i.e. bioenergetics) that influences colonization, multiplication, and the types of treatment/antimicrobials necessary to reduce listerial cell numbers. Role: Co-PI.

Completed Research Support (ended within the last three years) 0650199 NSF J. Kohn (PI) 03/01/07 – 02/28/09 PFI: Creating Value from Agricultural Materials for the Biomedical Market. This study was largely dedicated to the building of biopolymer blocks from native starch. We created new degradable biomaterials and developed a scientific understanding of how these materials function at surfaces and biological interfaces. Our role was to elucidate the ability of newly synthesized biopolymers to influence biofilm formation by human pathogens such as Salmonella and Escherichia coli Ol157:H7. Role: Co-PI. R21 AT002897-02 NIH M. Chikindas (PI) 01/01/07 – 12/31/09 Natural antimicrobials against bacterial vaginosis. The project was focused on the mechanistic study of an antimicrobial peptide, lactocin 160, derived from healthy vaginal Lactobacillus sp. This project resulted in the establishment of methodological approaches for elucidation of bacteriocins’ activity against G. vaginalis and was the first to report on the epivaginal in vitro model as a reliable substitution of the animal model for safety studies targeting vaginal applications. CAFT Cooperative Research and Development Program M. Chikindas (PI) 01/01/07 – 12/31/09 Natural antimicrobials for control of human pathogens. This research was dedicated to elucidating the synergy in the action of natural and nature-derived antimicrobials against the human pathogen Listeria monocytogenes. CAFT Cooperative Research and Development Program K. Uhrich (PI) 01/01/07 – 12/31/09 Natural antimicrobial polymers for control of biofilm formation by foodborne pathogens. The project identified physiological and biochemical changes in Salmonella leading to the arrest of biofilm formation under the pressure of control-released natural antimicrobials. Role: Co-PI.

PHS 398/2590 (Rev. 05/01) Page 1 Biographical Sketch Format Page

Principal Investigator: Wendie S. Cohick

BIOGRAPHICAL SKETCH Provide the following information for the key personnel in the order listed on Form Page 2.


NAME

Cohick, Wendie S. POSITION TITLE

Associate Professor



Cornell University, Ithaca NY B.S. 1977-1981 Animal ScienceUniversity of Illinois, Urbana-Champaign M.S. 1981-1983 Nutrition Cornell University, Ithaca NY Ph.D. 1983-1989 Nutritional Biochemistry University of NC School of Medicine, Chapel Hill Postdoc 1989-1993 Endocrinology

A. Positions and Honors. Positions and Employment 1993-1996 Research Instructor, UNC School of Medicine at Chapel Hill, Dept Medicine, Endocrinology 1996-2002 Assistant Professor, Biotech Center and Department of Animal Sciences, Rutgers University,

New Brunswick NJ 2001-present Member, Cancer Institute of New Jersey 2002-present Associate Professor, Biotech Center and Department of Animal Sciences, Rutgers University,

New Brunswick NJ Other Experience and Professional Memberships 1989 Member, Endocrine Society 2009 Member, American Association of Cancer Research 1998-2004 Editorial Board, Journal of Animal Science 2002-2005 Panel Member, DOD Breast Cancer Research Program, Experimental and Clinical Therapeutics 2003, 2009 Panel Member, USDA Competitive Grants Program 2004-2009 Panel Member, Cell Biology Concepts Review Panel, DOD Breast Cancer Research Program 2005 Panel Member, NIH PO1 Program Project Grant Review 2006-present Editorial Board, Endocrinology. 2006, 2007 Panel Member, DOD Breast Cancer Research Program, Cell Biology 2007-present Graduate Program Director, Endocrinology and Animal Biosciences, Rutgers University 2008 Panel Member, Cell Biology PreDoc Fellowship Review Panel, DOD Breast Cancer Res Pro B. Selected peer-reviewed publications. 1. Cohick WS, Plaut K, Sechen SJ, Bauman DE 1989 Temporal pattern of insulin-like growth factor-I

response to exogenous bovine somatotropin in lactating cows. Domest Anim Endocrinol 6:263-274 2. Plaut, K, Cohick WS, Bauman DE, Baxter RC 1991 Evaluation of interference by insulin-like growth

factor-I (IGF-I) binding. Domest Anim Endocrinol 6:263:274 3. Cohick WS, Clemmons DR 1991 Regulation of insulin-like growth factor binding protein synthesis and

secretion in a bovine epithelial cell line. Endocrinology 129:1347-1354 4. Cohick WS, McGuire MA, Clemmons DR, Bauman DE 1992 Regulation of IGF binding proteins in serum

and lymph of lactating cows by somatotropin. Endocrinology 130:1508-1514 5. Cohick WS, Clemmons DR. 1993 The insulin-like growth factors. Annu Rev Physiol 55:131-153

Principal Investigator/Program Director (Cohick, Wendie S.):

2PHS 398/2590 (Rev. 05/01) Page 2 Continuation Format Page

6. Cohick WS, Clemmons DR 1994 Enhanced expression of dihydrofolate reductase by bovine kidney epithelial cells results in altered cell morphology, IGF-I responsiveness and IGFBP-3 expression. J Cell Physiol 161:178-186

7. Cohick WS, Armstrong JD, Whitacre MD, Lucy MC, Harvey RW, Campbell RM 1996 Ovarian expression of insulin-like growth factor-I (IGF-I), IGF binding proteins and growth hormone receptor in heifers actively immunized against growth hormone releasing factor. Endocrinology 137:1670-1677

8. Cohick WS, Turner JD 1998 Regulation of IGF binding protein synthesis by a bovine mammary epithelial cell line. J Endocrinol 157:326-336

9. Cohick WS 1998 Role of the insulin-like growth factors and their binding proteins in lactation. J Dairy Sci 81:1769-1777

10. Cohick WS, Wang B, Verma P, Boisclair YR. 2000 Insulin-like growth factor (IGF-I) and cyclic AMP regulate IGF binding protein-3 gene expression by transcriptional and post-transcriptional mechanisms in mammary epithelial cells. Endocrinology 141:4583-4591.

11. Grill CJ, Cohick WS 2000 Insulin-like growth factor binding protein-3 mediates IGF-I action in a bovine mammary epithelial cell line independent of an IGF interaction. J Cellular Physiology 183:273-283

12. Grill CJ, Cohick WS, Sherman A. 2001 Postnatal development of the rat mammary gland is preserved during iron deficiency. J Nutrition 131:1444-1448.

13. Grill CJ, Sivaprasad U, Cohick WS. 2002 Constitutive expression of IGF binding protein-3 by mammary epithelial cells alters signaling through Akt and p70S6 kinase. J Mol Endocrinol 29:153-162.

14. Cornwell T, Cohick WS, Raskin I. 2004 Dietary Phytoestrogens and Health. Phytochemistry 65:995-1016. 15. Sivaprasad U, Fleming J, Verma PS, Hogan KA, Desury G, Cohick WS. 2004 Stimulation of IGF binding

protein-3 synthesis by IGF-I and transforming growth factor (TGF)-α is mediated by both phosphatidylinositol-3 kinase (PI3K) and MAPK pathways in mammary epithelial cells. Endocrinology 145:4213-4221.

16. Fleming JM, Leibowitz BJ, Kerr DE, Cohick WS. 2005 IGF-I differentially regulates IGF binding protein expression in primary mammary fibroblasts and epithelial cells. J Endocrinol 186:165-178. 17. Thorn SR, Purup S, Cohick WS, Vestergaard M, Sejrsen K, Boisclair YR. 2006 Leptin does not act directly on mammary epithelial cells in prepubertal dairy heifers. J Dairy Sci. 89:1467-1477. 18. Fleming JM, Desury G, Polanco T, Cohick WS 2006 IGF-I and epidermal growth factor receptors recruit

distinct upstream signaling molecules to enhance AKT activation in mammary epithelial cells. Endocrinology 147:6027-6035.

19. Fleming JM, Brandimarto JA, Cohick WS 2007 The mitogen-activated protein kinase pathway tonically inhibits both basal and IGF-stimulated IGF binding proten-5 production in mammary epithelial cells. J Endocrinol 194:349-359. 20. Loor, JJ and Cohick WS. 2009 ASAS Centennial Paper: Lactation Biology for the 21st Century. J Anim

Sci 87:812-824. 21. Leibowitz BJ and Cohick WS. 2009 Endogenous IGFBP-3 is required for both growth factor-stimulated

cell proliferation and cytokine-induced apoptosis in mammary epithelial cells. J Cell Phys 220:182-188. 22. Jetzt AE, Cheng J, Tumer NE, Cohick WS. 2009 Ricin A-chain induces apoptosis through c-Jun NH2- terminal kinase in non-transformed epithelial cells. Intl J Biochem Cell Biol 41:2503-2510. 23. Polanco TA, Crismale-Gann C, Reuhl KR, Sarkar DK, Cohick WS. 2010. Fetal alcohol exposure increases mammary tumor susceptibility and alters tumor phenotype in rats. Alcoholism: Clinical and Experimental Research (Under review). C. Research Support Current Reseach Support Funding Agency: USDA Type USDA-CSREES-2009-35206-05210 Period: 01/01/09-12/31/11 Role: Principle Investigator

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Thorn+SR%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Purup+S%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Cohick+WS%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Vestergaard+M%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Sejrsen+K%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Boisclair+YR%22%5BAuthor%5D

Principal Investigator/Program Director (Cohick, Wendie S.):

2PHS 398/2590 (Rev. 05/01) Page 2 Continuation Format Page

Title: Role of nuclear IGFBP-3 in stress-induced apoptosis in bovine mammary epithelial cells Total Direct Costs: $279,984 Effort: 25% This project examined the mechanisms by which nuclear IGFBP-3 interacts with cellular proteins to regulate apoptosis. Funding Agency: NIH Type: 5F31CA132620 Period: 01/01/08-12/31/10 Role: Principle Investigator Title: Effect of alcohol exposure in utero on mammary carcinogenesis Total Direct Costs: $85,320 Effort: 15% This project examines the effect of alcohol exposure during pregnancy on susceptibility to mammary carcinogenesis in the offspring. Funding Agency: NIH Type: R01-A1072425-01 Period: 03/01/07-2/28/12 Role: Co-Investigator Title: Mechanism of cytotoxicity of ricin Total Direct Costs: $1,271,220 Effort: 25% The goal of this project is to determine the molecular mechanisms or ricin cytotoxicity in mammalian cells Funding Agency: NJ Agricultural Experiment Station Period: 9/1/08-8/31/13 Role: Principal Investigator Title: Role of IGFs and their binding proteins in the bovine mammary gland Total Direct Costs: $25,000 Effort: 15% This project examine the role of IGFs and their binding proteins in growth, differentiation, and involution. Completed Research Support (last three years) Funding Agency: NIH Type: R21 AO068869-02 Period: 04/01/06-3/31/09 Role: Co-Investigator Title: Identification of the ribosomal target of Shiga-like toxins. Total Direct Costs: $250,000 Effort: 10% This project will determine the molecular mechanisms by which shiga-like toxins induce cell death in mammalian cells. Funding Agency: NIH Type: R21 A1059720 Period: 09/30/04 – 3/31/06 Role: Co-Investigator Title: Mechanism of action of ricin A chain Total Direct Costs: $250,000 Effort: 15% The goal of this project was to determine the molecular mechanisms by which ricin causes apoptosis in cells. Funding Agency: Busch Biomedical Research Grant (Rutgers) Period: 07/01/05-6/30/07 Role: Principal Investigator Title: Effect of IGF-I on estrogen induced mammary tumorigenesis in the ACI rat. Total Direct Costs: $25,000 This project examined the interactions between the IGF and estrogen systems in an in vivo model of estrogen- induced carcinogenesis.

BIOGRAPHProvide the following information for the key personnel and

Follow this format for each perso

HICd othon.

CAL SKETCher significant co DO NOT EXCEE

Hontributors in the ordED FOUR PAGES.

der listed on Form Page 2.

NAMEPaul R. Copeland

POSITION TITLE

Assistant Pr

E

rofessoreRA COMMONS USER NAMECopeland

Assistant Prrofessor

EDUCATION/TRAINING (Begin with baccalaureate or other initial pprofeessional educatioon, such as nursing, and include postdoctoral training.)

INSTITUTION AND LOCATION (DEGREE

(if applicable) YEAR(s) FIELD OF STUDY

Loyola University of Chicago B.S. 1990 BiologyUniversity of Virginia Ph.D. 1997 BiologyCleveland Clinic Foundation Post-Doc 1997-2002 Cell Biology

A. Personal Statement The projects described in this proposal are designed to decipher the mechanism by which the 21st amino acid, selenocysteine (Sec), is co-translationally incorporated into 25 human proteins. Specifically we plan to elucidate the role of the novel elongation factor, eEFSec, in distinguishing UGA-Sec codons from the UGA codons that specify translation termination. My background in basic molecular biology is particularly well suited to lead these projects, and my past productivity in the area of selenocysteine incorporation should lend confidence that we will successfully complete the goals outlined in this proposal. My work in the selenium field began during my postdoctoral stint at the Cleveland Clinic Foundation in Donna Driscoll’s lab. There I purified and cloned a novel essential factor required for Sec incorporation, thus laying the groundwork for all of the mechanistic studies published to date. Since starting my own group in 2002, we have made significant progress in determining the role of SBP2 in this process, and here we seek to bring our expertise to bear on the mechanism of SBP2L function and regulation. In summary, our previous work has established that my lab has been providing the leading edge research in selenium molecular biology. B. Positions and Honors.Positions• Assistant Professor, UMDNJ, Robert Wood Johnson Medical School, Department of Molecular

Genetics, Microbiology and Immunology, 2002 – present.• Project Scientist, Cleveland Clinic Foundation, Lerner Research Institute, Department of Cell

Biology, 2001-2002.• Research Associate, Cleveland Clinic Foundation, Lerner Research Institute, Department of Cell

Biology, Dr. Donna M. Driscoll, Principal Investigator. 2000-2001.• Postdoctoral Fellow, Cleveland Clinic Foundation, Lerner Research Institute, Department of Cell

Biology, Dr. Donna M. Driscoll, Principal Investigator. 1997-1999.• Graduate Student, University of Virginia, Department of Biology, Dr. Michael Wormington, Principal

Investigator. 1990-1996.• Summer Research Training Program, National Cancer Institute, Human Genetics Analysis Lab, Drs

Steven J. O'Brien and Michael Dean, Advisors, Summers of 1989 and 1990.• Undergraduate Research, Loyola University of Chicago, Dr. Howard Laten, Advisor, 1986-1990.

Awards• Cancer Institute of New Jersey New Investigator Award, 2002-2003• Elsa Albrecht Fellow Award for Best Manuscript in Cell Biology Department, Cleveland Clinic

Foundation, 2000.• Kepner Teaching Award, Biology Department, University of Virginia, 1992.• SRTP fellowship, National Cancer Institute 1989-1990.

Professional Associations • American Association for the Advancement of Science• The RNA Society • American Society for Biochemistry and Molecular Biology

B. Selected peer-reviewed publications (from a total of 26)Copeland, P.R., and Driscoll, D.M. (1999). Purification, redox sensitivity and RNA binding properties of SECIS-binding protein 2, a protein involved in selenoprotein biosynthesis. J. Biol Chem 274: 25447-25454.Copeland, P.R., Fletcher, J.E., Carlson, B.A., Hatfield, D.L., and Driscoll, D.M. (2000). A novel RNA binding protein, SBP2, is required for the translation of mammalian selenoprotein mRNAs. EMBO J. 19:306-314. PMCID: PMC305564Tujebajeva, R. M., Copeland, P.R., Xu, X-M., Carlson, B.A., Harney, J.W., Driscoll, D.M., Hatfield, D.L., and Berry, M.J. (2000). Decoding apparatus for eukaryotic selenocysteine insertion. EMBO Reports 1:158-163. PMCID: PMC1084265Fletcher, J.E., Copeland, P.R., and Driscoll, D.M. (2000) Polysome distribution of phospholipid hydroperoxide glutathione peroxidase mRNA: Evidence for a block in elongation at the UGA/selenocysteine codon. RNA 6:1573-1584. PMCID: PMC1370027Copeland, P.R., Stepanik, V.A., and Driscoll, D.M. (2001) Insights into mammalian selenocysteine incorporation: Domain structure and ribosome binding of SBP2. Mol. Cell. Biol. 21:1491-1498. PMC86695Fletcher, J.E., Copeland, P.R., Driscoll, D.M., Krol, A. (2001). The selenocysteine incorporation machinery: interactions between the SECIS RNA and the SECIS-binding protein SBP2 RNA, 7:1442-1453. PMCID: PMC1370188Copeland, P.R. (2003). Regulation of gene expression by stop codon recoding: selenocysteine. Gene. 312:17-25. PMCID: In ProgressMehta, A, Rebsch, C.M., Kinzy, S.A., Fletcher, J.E. and Copeland, P.R. (2004) Efficiency of Mammalian Sec incorporation. J. Biol. Chem. 279:38852-59. PMCID: In ProgressKinzy, S.A., Caban, K. and Copeland, P.R. (2005) Characterization of the SECIS binding protein 2 complex required for the co-translational insertion of selenocysteine in mammals. Nucl Acid Res. 33:5172-5180. PMCID: PMC1214547Caban, K., Kinzy, S.A. and Copeland, P.R. (2007) The L7Ae RNA binding motif is a multi-functional domain required for the ribosome-dependent Sec incorporation activity of SECIS binding protein-2. Mol Cell Biol, 27:6350-60. PMCID: PMC2099609Gupta, M. and Copeland, P.R. (2007) Functional analysis of the interplay between translation termination, selenocysteine codon context and SECIS binding protein 2, J Biol Chem. 2007 282(51):36797-807. PMCID: In ProgressBockhorn, J., Balar, B., Seitomer, E., He, D., Copeland, P.R. and Kinzy, T.G. (2008) Genome Wide Screen of Saccharomyces cerevisiae Null Allele Strains Identifies Genes Involved in Selenomethionine Resistance. PNAS, 105(46):17682-7. PMCID: PMC2584752

Donovan, J., Caban, K., Ranaweera, R., Gonzales-Flores, J.N. and Copeland P.R. (2008) A Novel Protein Domain Induces High Affinity Selenocysteine Insertion Sequence Binding and Elongation Factor Recruitment. J. Biol Chem. 283(50):35129-35139. PMID: PMC18948268Donovan, J., and Copeland, P.R. (2009) Evolutionary history of selenocysteine incorporation from the perspective of SECIS binding proteins. BMC Evol. Biol. 9:229 PMCID: PMC2746813Donovan, J. and Copeland, P.R. (2010) Threading the needle: getting selenocysteine into proteins. Antioxidant & Redox Signalling 12(7):881-92.Esposito, A, Mateyak, M., He, D., Lewis, M., Sasikumar, A.N., Hutton, J., Copeland, P.R. and Kinzy, T.G. (2010) Eukaryotic polyribosome profile analysis. J. Vis. Exp. in press.Donovan, J. and Copeland, P.R. (2010) The efficiency of selenocysteine incorporation is regulated by translation initiation factors. Submitted to J Mol Biol.

C. Research SupportACTIVE

NIH R01 GM077073 (Copeland, PI) 1/1/06 – 12/31/10 NIH/NIGMS Functional analysis of SBP2 and selenocysteine incorporationThe major goals of this project are to characterize the regulation of SBP2, a factor required for selenocysteine incorporation.

UMDNJ Foundation Bridging Grant (Copeland, PI)UMDNJ FoundationTranslational Control of Selenoprotein Synthesis 7/1/08 - 6/30/10 This award provides bridge funds to sustain activities between awards.

PENDINGNSF MCB 0950882 (Copeland, PI) 10/1/10 - 9/30/14 Characterization of novel selenocysteine insertion sequencesThe goal of this project is to characterize three novel SBP2 target RNAs in the human genome.

NIH 1R01GM094833-01 (Copeland, PI) 7/1/10 – 6/30/14 NIH/NIGMS Expanding The Genetic Code In YeastThe major goal of this project is to reconstitute the complete Sec incorporation machinery in yeast.

NIH 1R01GM095523-01 (Copeland, PI) 1/1/11 - 12/31/15NIH/NIGMSMolecular requirements for selenocysteine incorporation.The major goals of this project is to determine how the dynamic interplay between the two key factors required for selenocysteine incorporation: SBP2 and the Sec-specific elongation factor, eEFSec.

NIH 1R03AG038869-01 (Copeland, PI) 1/1/11 - 12/31/12Characterization of a Novel Protein Involved in Selenocysteine Incorporation.The major goal of this project is to identify molecular partners and the function of a novel SECIS binding protein, SBP2L.

PASTR21 GM074180 – (Kinzy, PI) 8/1/06 – 7/31/09NIH/NIGMSDevelopment of selenomethionine resistant yeastThe major goal of this project is to identify a method to achieve high-level substitution of methionine for selenomethionine for use in crystallographic studies.

R01 GM068077 (Copeland, PI) 8/1/03 – 7/31/09 NIH/NIGMS Translational Control of Selenoprotein SynthesisThe major goals of this project are to characterize the function of the factors required for selenocysteine incorporation.



NAME

Dougherty, Joseph P. eRA COMMONS USER NAME (credential, e.g., agency login)

dougherty

POSITION TITLE

Professor



New York University, New York, NY B.A. 1975 Biology

Yale University, New Haven, Ct. Ph.D. 1977-1982 Molecular Biophysics and Biochemistry


1983 - 1984 Post-doctoral Fellow, Universite Louis Pasteur, Advisor: Pierre Chambon 1985 - 1988 Post-doctoral Fellow, University of Wisconsin, Advisor: Howard M.Temin 1983 - 1985 American Cancer Society post-doctoral fellowship 1983 NSF-NATO post-doctoral fellowship in science (declined) 1983 Fogarty International Fellowship, NIH-French CNRS Program (declined) 1985 - 1987 NIH post-doctoral fellowship 1988 - 1994 Assist. Professor, Dept of Mol. Genetics & Microbiology, UMDNJ-RWJMS 1988 - 1994 Pew Scholars Award in the Biomedical Sciences 1988 - Present Member, Graduate Program in Microbiology, Rutgers University 1989 - 1994 NIH FIRST Award 1989 - 1991 March of Dimes Basil O'Connor Starter Research Award 1994 - 2000 Associate Professor, Dept of Mol. Genetics & Micro, UMDNJ-RWJMS 1994 Invited Professorship, Universite Louis Pasteur, Strasbourg, France 1997 – 1999 Member, Executive Committee for Graduate Program in Mol. Biosciences,

Rutgers/UMDNJ Joint Program 1999 Reviewer, Gene Therapy Vectorology Special Emphasis Panel, NIDDK 1999 Reviewer for Special Study Section for SBIR/STTR, NIH 2000 Reviewer for Medical Biochemistry Study Section, NIDDK 2000 Reviewer for Special Emphasis Panel, NIDDK 2000 - Present Professor, Dept of Mol. Genetics, Micro. & Immunology, UMDNJ-RWJMS 2002 - Present Director, Grad. Program in Mol. Genet., Micro. & Immuno, UMDNJ-RWJMS 2003 – Present Member, Executive Committee for Graduate Program in Mol. Biosciences,

Rutgers/UMDNJ Joint Program 2003 - 2009 Chairman, Institutional Biosafety Committee, UMDNJ-RWJMS

B. Selected publications from 2004.

1. Biswas, P., X. Jiang, A.L. Pacchia, J.P. Dougherty and S.W. Peltz. Programmed –1 ribosomal frameshifting as a target for antiretroviral therapy. Journal of Virology, 78: 2082-7(2004).

2. Chen, C.-C., A. Rivera, J.P. Dougherty and Y. Ron. Complete protection from relapsing experimental autoimmune encephalomyelitis. Blood 103(12):4616-8 (2004).

3. Duttagupta, R., B. Tian, C.J. Wilusz, D.t. Khounh, P. Soteropoulos, M. Ouyang, J.P. Dougherty, and S.W. Peltz. Global analysis of Pub1p targets reveals a coordinate control of gene expression through modulation of binding and stability. Molecular and Cellular Biology, 25:5499-5513 (2005).

4. Le Roy, F., T. Salehzada, C. Bisbal, J.P. Dougherty, and S.W. Peltz. A novel function for RNase L in regulating translation termination. Nature Structural and Molecular Biology,6:505-512 (2005).

5. Micheva-Viteva, S., A.L. Pacchia, Y. Ron, S.W. Peltz, and J.P. Dougherty. Human immunodeficiency virus type 1 latency model for high-throughput screening. Antimicrobial Agents and Chemotherapy, 49(12):5185-8 (2005).

6. S. Mukherjee, H. L. Lee, Y. Ron, and J. P. Dougherty. Proviral progeny of heterodimeric virions reveal a high crossover rate for human immunodeficiency virus type 2. Journal of Virology 80 (24):12402-12407 (2006).

7. J. Zhuang, S. Mukherjee, Y. Ron, and J. P. Dougherty. High rate of genetic recombination in murine leukemia virus: implications for influencing proviral ploidy. Journal of Virology 80 (13):6706-6711, (2006).

8. S. Mukherjee, H. L. Lee, A. L. Pacchia, Y. Ron, and J. P. Dougherty. A HIV-2-based self-inactivating vector for enhanced gene transduction. Journal of Biotechnology 127 (4):745-757 (2007).

9. Graci, J., J. Colacino, S.W. Peltz, and J.P. Dougherty and Z. Gu. Human immunodeficiency virus type 1 latency: targeted induction of proviral reservoirs. Antimicrobial Agents and Chemotherapy. Antimicrobial Agents and Chemotherapy 19(5):177-187 (2009).

10. Edelstein, L.C., Micheva-Viteva, S., and J.P. Dougherty. Activation of latent HIV by suberoylanilide hydroxamic acid (SAHA), an HDAC inhibitor approved for use to treat cutaneous T-cell lymphoma. AIDS Research and Human Retroviruses, 25 (9):883-887 (2009).

11. Clartag, A., C.-C. Chen, J.P. Dougherty, and Y. Ron. Cross-reactive antibodies induced against xenogeneic IgA can cause selective IgA deficiency. Autoimmunity. In Press (2009).

12. Kobayashi, Y., J. Zhuang, S. Peltz, and J.P. Dougherty. Identification of a cellular factor that modulates HIV-1 programmed ribosomal frameshifting. Submitted (2009).

13. B. Phelan, L. Edelstein, R. Lee, S. Micheva-Viteva, Y. Ron, and J.P. Dougherty. Latent human immunodeficiency virus type-1 provirus activation by microtubule binding agents. In Preparation (2009).

14. Micheva-Viteva, S., L. C. Edelstein, J. Breslin, A.L. Pacchia, Y. Ron, S.W. Peltz, Z. Gu, and J.P. Dougherty. High-throughput screening of a small molecule library uncovers a compound that activates latent HIV-1 via a novel mechanism. In Preparation (2009).

15. G.M. DiGioia, B.D. Phelan, T. Lavoie, W.A. Clark, J.P. Dougherty, and S. Pestka. The interferon-alpha family of proteins shows variable antiviral potencies against Human Immunodeficiency Virus Type 1. In Preparation (2009)

Current Research Support 1R01AI081307 Dougherty (PI) 12/01/08-11/30/13 NIH/NIADS Gene Regulation using Novel Drugs Modulating Premature Translational Termination. Role: Principal Investigator 1R01AI070039 Dougherty (PI) 6/01/06-05/31/10 NIH/NIADS High Throughput Screening to Identify Antagonists of HIV-1 Latency .Role: Principal Investigator 487-09 Dougherty (PI) 6/01/09-5/31/10 Foundation of UMDNJ Chemical Genomics to Exploit HIV-1 Programmed -1 Ribosomal Frameshifting as a Novel Antiviral Target. Role: Principal Investigator P01 AI057596 Pestka (PD) 07/01/04 – 06/30/10 National Institute of Allergy and Infectious Diseases Translational Regulation by the TNF Alpha AU-rich Element Role: Project #3 Acting Principal Investigator


Follow this format for each person. DO NOT EXCEED TWO PAGES.

NAME Duffy, Siobain Marie Deirdre eRA COMMONS USER NAME SIOBAINDUFFY

POSITION TITLE Assistant Professor



Rutgers University, New Brunswick, NJ BA 2000 Molecular Biology & Biochemistry

Yale University, New Haven, CT MS 2003 Ecology & Evolutionary Biology

Yale University, New Haven, CT PhD 2006 Ecology & Evolutionary Biology

The Pennsylvania State University, University Park, PA 2007-2009 Viral Evolution


Positions and Employment 1995-1996 Student Trainee, Macromolecular Engineering Lab, Hoffman-LaRoche, Nutley, NJ 1997 Lab Technician I, Protein Engineering Lab, ABL-BRP National Cancer Institute, Frederick, MD 2001-2006 Howard Hughes Medical Institute Predoctoral Fellow, Yale University, New Haven, CT 2004-2006 Visiting Scholar, Department of Biology, University of North Carolina, Chapel Hill, NC 2007-2009 NSF Postdoctoral Fellow in Biological Informatics, Department of Biology,

The Pennsylvania State University, University Park, PA 2009- Assistant Professor, Department of Ecology, Evolution & Natural Resources, Rutgers University Other Experience and Professional Memberships 2003- Member, American Society for Microbiology 2003-2005 Editorial Board, Yale Journal of Biology and Medicine 2006- Member, Bacteriophage Ecology Group 2006-2007 Contributor, Bacteriophage Ecology Group News 2008- Member, Society for Molecular Biology and Evolution 2008- Member, Plant Virus Ecology Network 2008- Editorial Board, Applied and Environmental Microbiology Selected Honors 2000 Fulbright Grant, for study in Germany 2000 NSF Graduate Fellowship (declined to accept the HHMI Predoctoral Fellowship) 2001-2006 Howard Hughes Medical Institute Predoctoral Fellowship 2006 Raymond W. Sarber Award for graduate research excellence and potential,

American Society for Microbiology 2007 John Spangler Nicholas Prize for outstanding dissertation research, Yale University 2008 Postdoctoral poster prize, Society for Molecular Biology and Evolution annual meeting 2008 Women’s Career Development Grant for postdoctoral research excellence and potential,

American Society for Microbiology

B. Peer-reviewed publications (in chronological order).

1. S. Duffy, K.-L. Tsao and D.S. Waugh. 1998. Site-specific, enzymatic biotinylation of recombinant proteins in Spodoptera frugiperda cells using biotin acceptor peptides. Analytical Biochemistry. 262:122-128.

2. S. Duffy, D.W. Schaffner, J. Churey and R.W. Worobo 2000. Analysis and modeling of the variability associated with UV inactivation of Escherichia coli in apple cider. Journal of Food Protection. 63:1587–1590.

3. H.E. Uljas, D.W. Schaffner, S. Duffy and S.C. Ingham. 2001. Modeling of combined processing steps for reducing Escherichia coli O157:H7 populations in apple cider. Applied and Environmental Microbiology. 67:133-141. PMCID92532

4. S. Duffy and D.W. Schaffner. 2001. Modeling the survival of Escherichia coli O157:H7 in apple cider using probability distribution functions for quantitative risk assessment. Journal of Food Protection. 64:599–605.

5. M.K. Llaudes, L. Zhao, S. Duffy and D.W. Schaffner. 2001. Simulation and modelling of the effect of small inoculum size on time to spoilage by Bacillus stearothermophilus. Food Microbiology. 18:395-405.

6. A.S. Battey, S. Duffy and D.W. Schaffner. 2001. Modelling mould spoilage in cold-filled ready-to-drink beverages by Aspergillus niger and Penicillium spinulosum. Food Microbiology. 18:521-529.

7. A.S. Battey, S. Duffy and D.W. Schaffner. 2002. Modeling yeast spoilage in cold-filled ready-to-drink beverages. Applied and Environmental Microbiology. 68:1901-1906. PMCID123824

8. M.L. Caipo, S. Duffy, L. Zhao and D.W. Schaffner. 2002. Inoculum size affects germination of Bacillus megaterium. Journal of Applied Microbiology, 92:879-884.

9. T.M. Ng, E. Viard, M.L. Caipo, S. Duffy and D.W. Schaffner. 2002. Expansion and validation of a predictive model for the growth of Bacillus stearothermophilus in military rations. Journal of Food Science. 67:1872-1878.

10. S. Duffy and D.W. Schaffner. 2002. Modeling the environmental contamination of apples with Escherichia coli O157:H7. International Journal of Food Microbiology. 78:245-255.

11. D.W. Schaffner, J. McEntire, S. Duffy, R. Montville, and S. Smith. 2003. Monte Carlo simulation of the shelf life of pasteurized milk as affected by temperature and initial concentration of spoilage organisms. Food Protection Trends. 23:1014-1021.

12. S. Duffy, P.E. Turner and C.L. Burch. 2006. Pleiotropic costs of niche expansion in the RNA bacteriophage φ6. Genetics. 172:1-7. PMCID1456241

13. S. Duffy, C.L. Burch and P.E. Turner. 2007. Evolution of host specificity drives reproductive isolation among RNA viruses. Evolution. 61:2614-2622.

14. S. Duffy and E.C. Holmes. 2007. Multiple introductions of the old world begomovirus Tomato yellow leaf curl virus into the new world. Applied and Environmental Microbiology. 73:7114-7117. PMCID2074955

15. S. Duffy and E.C. Holmes. 2008. Phylogenetic evidence for rapid rates of molecular evolution in the single-stranded DNA begomovirus Tomato yellow leaf curl virus (TYLCV). Journal of Virology. 82:957-965. PMCID2224568

16. S. Duffy, L.A. Shackelton and E.C. Holmes. 2008. Rates of evolutionary change in viruses: patterns and determinants. Nature Reviews Genetics. 9:267-276.

17. S. Duffy and E.C. Holmes. 2009. Validation of high rates of nucleotide substitution in geminiviruses: Phylogenetic evidence from East African cassava mosaic viruses. Journal of General Virology. 90:1539-1547.

18. G. Harkins, W. Delport, S. Duffy, N. Wood, A,L. Monjane, B.E. Owor, L. Donaldson, S. Saumtally, S. Verabudren, G. Triton, P.G. Markham, R.W. Briddon, D.N. Shepherd, E.P. Rybicki, D.P. Martin and A. Varsani. 2009. Experimental evidence indicating that mastreviruses probably did not co-diverge with their hosts. Virology Journal. 6:104.

19. K. Rosario, S. Duffy and M. Breitbart. Diverse circovirus-like genome architectures revealed by environmental metagenomics. Journal of General Virology. In press.

20. J.M. Cuevas, S. Duffy and R. Sanjuán. Mutation rate of phiX174. Genetics. In press. 21. G.W. Harkins, D.P. Martin, S. Duffy, A.L. Monjane, D.N. Shepherd, O.P. Windram, B.E. Owor, L.

Donaldson, T. van Antwerpen, R.A. Sayed, B. Flett, M. Ramusi, E.P. Rybicki, M. Peterschmitt and A. Varsani. Dating the origins of the maize-adapted strain of maize streak virus, MSV-A. Journal of General Viology. In press.

C. Research Support Ongoing Research Support None Completed Research Support 06-30707 Duffy (PI) 01/01/07 – 12/31/08 NSF DBI Genomic Architecture, Mutational Bias and the Evolution of DNA Viruses. This study estimated the rate of evolution of several small DNA viruses, and compared the spectra of their substitutions to RNA and large DNA viruses. Role: PI 04-08000 Turner (PI) 09/01/04 – 08/31/06 NSF DEB Evolution of Generalism and Specialism in the dsRNA Bacteriophage Phi6. This study used experimental evolution to test the application of evolutionary theory to emerging, host-shifting viruses, using the model RNA virus phage Phi6. Role: Co-PI



NAME Richard H. Ebright eRA COMMONS USER NAME EBRIGHT1




Harvard University, Cambridge, MA

Harvard University, Cambridge, MA (with Jon Beckwith)

A.B.

Ph.D.

1977-1981

1981-1987

Biology (summa cum laude)

Microbiology and Molecular Genetics

Professional Positions: 1984-1987 Junior Fellow, Society of Fellows, Harvard University, Cambridge, MA 1987- Laboratory Director, Waksman Institute of Microbiology, Piscataway NJ 1987-1992 Assistant Professor, Department of Chemistry, Rutgers University, New Brunswick, NJ 1992-1995 Associate Professor, Department of Chemistry, Rutgers University, New Brunswick, NJ 1995- Professor, Department of Chemistry, Rutgers University, New Brunswick, NJ 1997- Investigator, Howard Hughes Medical Institute

Honors: Phi Beta Kappa (1980); Searle Scholar Award (1989); Johnson and Johnson Discovery Research Fellowship (1990); American Society for Biochemistry and Molecular Biology Schering-Plough Award (1995); Academic Press Walter J. Johnson Prize (1995); American Academy of Microbiology (1996); Rutgers University Board of Trustees Award (1998); American Association for the Advancement of Science Fellow (2004)

Selected Publications (of 134): Zhou, Y., Busby, S., and Ebright, R. (1993) Identification of the functional subunit of a dimeric transcription

activator protein by use of "oriented heterodimers." Cell 73, 375-379. Heyduk, T., Lee, J., Ebright, Y., Blatter, E., Zhou, Y., and Ebright, R. (1993) CAP interacts with RNA

polymerase in solution in the absence of promoter DNA. Nature 364, 548-549. Chen, Y., Ebright, Y., and Ebright, R. (1994) Identification of the target of a transcription activator protein by

protein-protein photocrosslinking. Science 265, 90-92. Pendergrast, P.S., Ebright, Y., and Ebright, R. (1994) High-specificity DNA cleavage agent: design and

application to kilobase and megabase DNA substrates. Science 265, 959-961. Blatter, E., Ross, W., Tang, H., Gourse, R., and Ebright, R. (1994) Domain organization of RNA polymerase α

subunit: C-terminal 85 amino acids constitute a domain capable of dimerization and DNA binding. Cell 78, 889-896.

Busby, S. and Ebright, R. (1994) Promoter structure, promoter recognition, and transcription activation in prokaryotes. Cell 79, 743-746.

Niu, W., Kim, Y., Tau, G., Heyduk, and Ebright, R. (1996) Transcription activation at Class II CAP-dependent promoters: two interactions between CAP and RNA polymerase. Cell 87, 1123-1134.

Miller, A., Wood, D., Ebright, R., and Rothman-Denes, L. (1997) RNA polymerase β': a target for DNA-binding-independent activation. Science 275, 1655-1657.

Kim, T.-K., Ebright, R., and Reinberg, D. (2000) Mechanism of ATP-dependent promoter melting by transcription factor IIH. Science 288, 1418-1421.

Naryshkin, N., Revyakin, A., Kim, Y., Mekler, V., and Ebright, R. (2000) Structural organization of the RNA polymerase-promoter open complex. Cell 101, 601-611.

Mukhopadhyay, J., Kapanidis, A., Mekler, V., Kortkhonjia, E., Ebright, Y., and Ebright, R. (2001) Translocation of σ70 with RNA polymerase during transcription: fluorescence resonance energy transfer assay for movement relative to DNA. Cell 106, 453-463.

Mekler, V., Kortkhonjia, E., Mukhopadhyay, J., Knight, J., Revyakin, A., Kapanidis, A., Niu, W., Ebright, Y., Levy, R., and Ebright, R. (2002) Structural organization of RNA polymerase holoenzyme and the RNA polymerase-promoter open complex. Cell 108, 599-614.

Benoff, B., Yang, H., Lawson, C., Parkinson, G., Liu, J., Blatter, E., Ebright, Y., Berman, H., and Ebright, R. (2002) Structural basis of transcription activation: structure of the CAP-αCTD-DNA complex. Science 297, 1562-1566.

Mukhopadhyay, J., Sineva, E., Knight, J., Levy, R., and Ebright, R. (2004) Antibacterial peptide microcin J25 inhibits transcription by binding within and obstructing the RNA polymerase secondary channel. Mol. Cell. 14, 739-751.

Tuske, S., Sarafianos, S., Wang, X., Hudson, B., Sineva, E., Mukhopadhyay, J., Birktoft, J, Leroy, O., Ismail, S., Clark, A., Dharia, C., Napoli, A., Laptenko, O., Lee, J., Borukhov, S., Ebright, R., and Arnold, E. (2005) Inhibition of bacterial RNA polymerase by streptolydigin. Cell 122, 541-552.

Revyakin, A., Liu, C., Ebright, R. & Strick, T. (2006) Abortive initiation and productive initiation by RNA polymerase involve DNA scrunching. Science 314, 1139-1143.

Kapanidis, A., Margeat, E., Ho, S.O., Kortkhonjia, E., Weiss, S. & Ebright, R. (2006) Initial transcription by RNA polymerase proceeds through a DNA-scrunching mechanism. Science 314, 1144-1147.

Mukhopadhyay, J., Das, K., Ismail, S., Koppstein, D., Jang, M., Hudson, B., Sarafianos, S., Tuske, S., Patel, J., Jansen, R., Irschik, H., Arnold, E., and Ebright, R. (2008) The RNA polymerase "switch region" is a target of inhibitors Cell 135, 295-307.

Goldman, S., Ebright, R., and Nickels, B. (2009) Direct detection of abortive RNA transcripts in vivo. Science 324, 927-928.

Hudson, B., Quispe, J., Lara, S., Kim, Y., Berman, H., Arnold, E., Ebright, R., and Lawson, C. (2009) Three-dimensional structure of an intact activator-dependent transcription initiation complex. Proc. Natl. Acad. Sci. USA 106, 19830-19835.

Research Support: Bacterial Transcription Complexes NIH-NIGMS, R01-GM41376 (Ebright) 12/01/04-11/30/08 ($770 K direct for last three years) The major goal of this project is analysis of the mechanism of bacterial transcription initiation: i.e., kinetic photocrosslinking to define the mechanism of entry of RNA polymerase into promoter DNA, and single-molecule fluorescence resonance energy transfer and single-molecule nanomanipulation to define the mechanism of escape of RNA polymerase from promoter DNA.

Small-Molecule Inhibitors of Bacterial RNA Polymerase: "Switch Region" NIH-NIAID, R01-AI072766 (Ebright) 01/01/07-12/31/2011 ($1160 K direct for last three years [$410 K for Ebright component]) The major goal of this project is to identify and characterize small-molecules that inhibit bacterial RNA polymerase through interactions with the "switch region," a structural element that mediates conformational changes required for RNA polymerase to interact with DNA.

Small-Molecule Inhibitors of Mycobacterium tuberculosis RNA polymerase Global Alliance for TB Drug Development (Ebright) 09/09/09-06/30/10 ($566 K direct for last three years [$298 K for Ebright component]) The goal of this project is to provide a comprehensive evaluation of M. tuberculosis RNA polymerase as a target for anti-tuberculosis drug discovery

Antibacterial Drug Discovery Johnson & Johnson Pharmaceutical R & D (unrestricted gift) (Ebright) 07/06/09-06/30/10 ($65 K direct external for last three years) The major goal of this project is initial characterization of newly identified classes of inhibitors of bacterial RNA polymerase.

Investigatorship Howard Hughes Medical Institute (Ebright) 12/15/97-01/31/13 ($2380 K direct for last three years)



NAME

EDERY, Isaac eRA COMMONS USER NAME

IEDERY

POSITION TITLE

Professor



McGill University, Montreal, Canada B. Sc. 1981 Biochemistry McGill University, Montreal, Canada Ph.D. 1988 Gene Expression Brandeis University, Waltham, MA Postdoc 1989-93 Circadian Biology

A. Academic Positions. 4/07-present Professor, Department of Molecular Biology and Biochemistry, Rutgers University 4/00-3/07 Associate Professor, Department of Molecular Biology and Biochemistry, Rutgers University 11/30-present Member, Joint Graduate Program in Cell & Developmental Biology, Rutgers University and

UMDNJ 7/99-present Member, Graduate Program in Physiology and Neurobiology, Rutgers University and UMDNJ 1/94-present Member, Consolidated Graduate Program in the Molecular Biosciences, Rutgers University and

UMDNJ 1/94-present Member, Graduate Program in Microbiology and Molecular Genetics, Rutgers University 9/93-present Resident Member, Center for Advanced Biotechnology and Medicine 9/93-4/00 Assistant Professor, Department of Molecular Biology and Biochemistry, Rutgers University B. Selected publications

1. Edery, I., Humbelin, M., Darveau, A., Lee, K.A.W., Milburn, S., Hershey, J.W.B., Trachsel, H. and Sonenberg, N. (1983). Involvement of eIF-4A in the cap recognition process. J. Biol. Chem. 258, 11398-11403.

2. Edery, I., Lee, K.A.W. and Sonenberg, N. (1984). Functional characterization of eukaryotic mRNA cap binding complex: Effects on translation of capped and naturally uncapped RNAs. Biochemistry 23, 2456-2462.

3. Sarkar, G., Edery, I., Gallo, R. and Sonenberg, N. (1984). Preferential stimulation of rabbit �-globin mRNA translation by a cap binding protein complex. Biochemica et Biophysica Acta. 783, 122-129.

4. Lee, K.A.W., Edery, I. and Sonenberg, N. (1985). Isolation and structural characterization of cap binding proteins from poliovirus-infected HeLa cells. J. Virol. 54, 515-524.

5. Lee, K.A.W., Edery, I., Hanecak, R., Wimmer, E. and Sonenberg, N. (1985). Poliovirus protease 3C (P3-7c) does not cleave P220 of the eukaryotic mRNA cap binding protein complex. J. Virol. 55, 489-493.

6. Altmann, M., Edery, I., Sonenberg, N. and Trachsel, H. (1985). Purification and characterization of protein synthesis initiation factor eIF-4E from yeast Saccharomyces cerevisiae. Biochemistry 24, 6085-6089.

7. Sarkar, G., Edery, I. and Sonenberg, N. (1985). Photoaffinity labeling of the cap binding protein complex with ATP/dATP. J. Biol. Chem. 260, 13831-13837.

8. Edery, I. and Sonenberg, N. (1985). Cap-dependent splicing in a HeLa nuclear extract. Proc. Natl. Acad. Sci. USA 82, 7590- 7594.

9. McCubbin, W.D., Edery, I., Altmann, M., Sonenberg, N. and Kay, C.M. (1988). Circular dichroism and fluorescence studies on protein synthesis initiation factor eIF-4E, and two mutant forms from the yeast Saccharomyces cerevisiae. J. Biol. Chem. 263, 17663-17671.

10. Edery, I., Altmann, M. and Sonenberg, N. (1988). High level expression in E. coli of functional cap binding eukaryotic initiation factor eIF-4E and affinity purification using a simplified cap analog affinity matrix. Gene 74, 517-525.

11. Altmann, M., Edery, I., Trachsel, H. and Sonenberg, N. (1988). Site-directed mutagenesis of the tryptophan residues in yeast eukaryotic initiation factor 4E: effects on cap binding activity. J. Biol. Chem. 263, 17229-17232.

12. Edery, I., Petryshyn, R. and Sonenberg, N. (1989). Activation of double-stranded RNA dependent kinase (dsI) by the TAR region of HIV-1 mRNA: A novel translational control mechanism. Cell 56, 303-312.

13. McCubbin, W.D., Edery, I., Altmann, M., Sonenberg, N. and Kay, C.M. (1989). Circular dichroism and fluorescence studies on five mutant forms of protein synthesis initiation factor eIF-4E, from the yeast Saccharomyces cerevisiae. FEBS Letts. 245, 261-266.

14. Roy, S., Katze, M.G., Parkin, N.T., Edery, I., Hovanessian, A.G. and Sonenberg, N. (1990). Control of the interferon-induced 68-kilodalton protein kinase by the HIV-1 tat gene product. Science 247, 1216-1219.

15. Rozen*, F., Edery*, I., Meerovitch, K., Dever, T.E., Merrick, W.C. and Sonenberg, N. (1990). Bidirectional RNA helicase activity of eukaryotic translation initiation factors 4A and 4F. Mol. Cell. Biol. 10, 1134-1144. (* equal contribution by authors).

16. Rutila, J.E., Edery, I., Hall, J.C. and Rosbash, M. (1992). The analysis of new short-period circadian rhythm mutants suggests features of D. melanogaster period gene function. J. Neurogenet. 8, 101-113.

17. Huang, Z.J., Edery, I. and Rosbash, M. (1993). PAS is a dimerization domain common to Drosophila Period and several transcription factors. Nature 364, 259-262.

18. Edery, I., Rutila, J.E. and Rosbash, M. (1994). Phase shifting of the circadian clock by induction of the Drosophila period protein. Science 263, 237-240.

19. Edery, I., Zweibel, L.J., Dembinska, M. and Rosbash, M. (1994). Temporal phosphorylation of the Drosophila period protein. Proc. Natl. Acad. Sci. USA 91, 2260-2264.

20. Edery, I., Chu, L.L., Altman, M., Sonenberg, N. and Pelletier, J. (1995). An efficient strategy to isolate full-length cDNAs based on a mRNA cap retention procedure (CAPture). Mol. Cell. Biol. 15, 3363-3371.

21. Lee, C., Parikh, V., Itsukaichi, T., Bae, K. and Edery, I. (1996). Resetting the Drosophila clock by photic regulation of PER and a PER-TIM complex. Science 271, 1740-1744.

22. Majercak, J., Kalderon, D. and Edery, I. (1997). Drosophila melanogaster deficient in protein kinase A manifests behavior-specific arrhythmic behavior but normal clock function. Mol. Cell. Biol. 17, 5915-5922.

23. Sidote, D., Majercak, J. Parikh, V. and Edery, I. (1998). Differential effects of light and heat on the Drosophila circadian clock proteins PER and TIM. Mol. Cell. Biol. 18, 2004-2013.

24. Lee, C., Bae, K. and Edery, I. (1998). The Drosophila CLOCK protein undergoes daily rhythms in abundance, phosphorylation, and interactions with the PER-TIM complex. Neuron. 21, 857-867.

25. Bae, K., Lee, C., Sidote, D., Chuang, K.-Y. and Edery, I. (1998). Circadian regulation of a Drosophila homolog of the mammalian Clock gene: PER and TIM function as positive regulators. Mol. Cell. Biol. 18, 6142-6151.

26. Sidote, D. and Edery, I. (1999). Heat-induced degradation of PER and TIM in Drosophila bearing a conditional allele of the heat shock transcription factor gene. Chronobiology International 16, 519-525.

27. Lee, C., Bae, K. and Edery, I. (1999). PER and TIM inhibit the DNA binding activity of a dCLOCK-CYC heterodimer without disrupting formation of the heterodimer: A basis for circadian transcription. Mol. Cell. Biol. 19, 5316-5325.

28. Majercak, J., Sidote, D., Hardin, P.H. and Edery, I. (1999). How a circadian clock adapts to seasonal decreases in temperature and day length. Neuron 24, 219-230.

29. Bae, K., Lee, C., Hardin, P.H. and Edery, I. (2000). dCLOCK is present in limiting amounts and likely mediates daily interactions between the dCLOCK-CYC transcription factor and the PER-TIM complex. J. of Neurosci. 20, 1746-1753.

30. Kim, E.Y., Bae, K., Ng, F.S., Glossop, N.R.J., Hardin, P.E. and Edery, I. (2002). Drosophila CLOCK protein is under posttranscriptional control and influences light-induced activity. Neuron 34, 69-81.

31. Ko Wan, H., Jiang, J. and Edery, I. (2002). A role for Slimb in the degradation of Drosophila PERIOD protein phosphorylated by DOUBLETIME. Nature 420, 673-678.

32. Akten, B., E. Jauch, G. K. Genova, E. Y. Kim, I. Edery, T. Raabe, F. R. Jackson. (2003). A role for CK2 in the Drosophila circadian oscillator. Nature Neurosci. 6, 251-257.

33. Majercak, J., Chen, W.-F. and Edery, I. (2004). Splicing of period 3’ terminal intron is regulated by light, circadian clock factors and phospholipase C. Mol. Cell. Biol. 24, 3359-3372.

34. Ko Wan, H. and Edery, I. (2005). Analyzing the degradation of PERIOD protein by the ubiquitin-proteasome pathway in cultured Drosophila cells. Meth. Enzymol. 393, 394-408.

35. Kim, E.Y. and Edery, I. (2006). Balance between DBT/CKIε kinase and protein phosphatase activities regulate phosphorylation and stability of Drosophila CLOCK protein. Proc. Natl. Acad. Sci. 103, 6178-6183.

36. Chen, W.F., Majercak, J. and Edery, I. (2006). Clock-gated photic stimulation of timeless expression at cold temperatures and seasonal adaptation in Drosophila. J. Biol. Rhythms 21, 256-271.

37. Bae, K. and Edery, I. (2006). Regulating a circadian clock’s period, phase and amplitude by phosphorylation; insights from Drosophila. J. Biochemistry (Tokyo) 140, 609-617.

38. Kim, E.Y., Ko Wan, H., Yu, W., Hardin, P.E. and Edery, I. (2007). A DOUBLETIME kinase binding domain on the Drosophila PERIOD protein is essential for its hyperphosphorylation, transcriptional repression and circadian clock function. Mol. Cell. Biol. 27, 5014-5028.

39. Edery, I. (2007). A blend of two circadian clock, seasoned to perfection. Cell 129, 21-23. 40. Ko, H.W., DiMassa, S., Kim, E.Y. and Edery, I. (2007). Cis-combination of the classic perS and perL mutations

results in arrhythmic Drosophila with ectopic accumulation of constitutive hyperphosphorylated PERIOD protein. J. Biol. Rhythms 22, 488-501.

41. Chen, W.F., Low, K.H., Lim, C. and Edery, I. (2007). Thermosensitive splicing of a clock gene and seasonal adaptation. Cold Spring Harb. Symp. Quant. Biol. 72, 599-606.

42. Lee, J.-E. and Edery, I. (2008). Circadian regulation in the ability of Drosophila to combat pathogenic infections. Curr. Biol. 18, 195-199.

43. Yang, M., Lee J.-E., Padgett, R.W. and Edery. I. (2008). Circadian regulation of a limited set of conserved microRNAs in Drosophila. BMC Genomics 9:83.

44. Chiu, J., Vanselow, J.T., Kramer, A. and Edery, I. (2008). The phospho-occupancy of an atypical SLIMB binding site on PERIOD that is phosphorylated by DOUBLETIME controls the pace of the clock. Genes & Dev. 22, 1758-1772.

45. Low, K.H., Lim, C., Ko, H.-W. and Edery, I (2008). Natural variation in the splice site strength of a clock gene and species-specific thermal adaptation. Neuron 60, 1054-1067.

46. Edery, I. (2009) A stretch from the periphery helps brain clocks feel the daily heat. Neuron 64:157-60. 47. Chiu, J., Pike, D., Low, K.H. and Edery, I. (2010). Analyzing daily activity rhythms in Drosophila. JoVE (In Press).

C. Research Support (last three years) NIH (3 R01 NS042088); Seasonal Adaptation of a Circadian Clock; July 1, 2010-June 30, 2014 Direct costs/year: $218,750 Role on project: PI NIH (2R56NS042088-09); Seasonal Adaptation of a Circadian Clock; July 1, 2009-June 30, 2010 Direct costs/year: $250,000 Role on project: PI NIH (R01 NS034958); Clock Mechanism Underlying Drosophila Rhythmic Behavior; 02/15/08-01/31/12 Direct costs/year: $218,750 Role on project: PI NIH (K99 NS061952); The role of clock protein phosphorylation and degradation in circadian biology; 04/01/08-03/31/13 Direct costs: $80,000 (first 2 years); $160,000 (last 3 years) Awarded to: Dr. Joanna Chiu, postdoctoral fellow in Edery lab Role on project: Co-PI NIH (2R01 NS34958); Clock Mechanism Underlying Drosophila Rhythmic Behavior; January 1, 2004-December 31,

2007 Direct costs: $925,000 Role on project: PI NIH/NRSA Fellowship (F32 NS049862); Role of PER Phosphorylation in Circadian Biology; August 1, 2005-July 31,

2007 FY2005: $43,976 ($37,476 stipend plus $6500 institutional allowance) Awarded to: Joanna Chiu Role on project: Co-PI NIH, Neuroscience Training Grant (T32-MH019957-06A2); Molecular and Developmental Basis of Mental Illness; July 1,

2003-June 30, 2008 Direct costs/year: $183,055 Role on project: Co-PI (coordinator: Dr. John Pintar, Department of Neuroscience, UMDNJ) NIH (2R01 NS/MH42088); Seasonal Adaptation of a Circadian Clock; March 11, 2005-February 28, 2009 Direct costs: $925,000 Role on project: PI NIH (3 R01 NS042088-06S2); Seasonal Adaptation of a Circadian Clock; June 1, 2006-March 31, 2009 Direct costs: $175,000 Role on project: PI Sponsor: NIH, P30NS046593 Title: Establishment of University of Medicine and Dentistry (UMDNJ) Neuroproteomic Core Facility Period: September 15, 2004-June 30, 2009 Direct costs/year: $378,132 Role on project: Co-PI (coordinator: Dr. Hong Li, University of Medicine and Dentistry of New Jersey) Busch Biomedical Research Grant, Rutgers University; MicroRNAs in circadian rhythms and immune responses; July 1,

2006-June 30, 2008 Direct costs: $23,800



NAME Huizhou Fan

eRA COMMONS USER NAME FANHUIZHOU




Hunan Medical University M.D. (Equivalence)

1978-1983 Medicine

Hunan Medical University M.Sc. 1983-1986 Clinical microbiology University of Manitoba Ph.D. 1990-1994 Medical microbiology Manitoba Institute of Cell Biology 1995-1997 Cancer Biology University of California San Francisco 1998-2000 Cell Signaling

A. Positions and Honors. Positions and Employment: 1990 – 1994 Graduate research assistant, University of Manitoba, Winnipeg, Canada 1994 – 1997 Postdoctoral fellow, Manitoba Institute of Cell Biology, Winnipeg, Manitoba, Canada 1997 – 2000 Postgraduate researcher, University of California, San Francisco, CA 2001 – 2001 Assistant research cell biologist, University of California, San Francisco, CA 2001 – Assistant professor, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ 2001 – Member, Joint Molecular BioScience Graduate Education Program of Rutgers/RWJMS 2002 – Member, Cancer Institute of New Jersey, Piscataway, NJ 2002 – Member, UMDNJ-RWJMS Gerontological Institute, Piscataway, NJ

Professional Memberships: 1991 – 1994 American Society for Microbiology 2000 – American Society for Cell Biology 2002 – American Association for the Advancement of Science 2003 – American Association for Biochemistry and Molecular Biology

Major Academic Services: 2002 – 2008 Chair and/or member of advisory committees for 13 PhD students 2003 – 2008 Journal reviewer, Journal of Biological Chemistry, BBA - Molecular Cell Research, Journal of

Molecular Microbiology and Biotechnology, Traffic, DNA and Cell Biology, Medical Science Monitor, Journal of Enzyme Inhibition & Medicinal Chemistry

2004 Reviewer for Susan G. Komen Breast Cancer Foundation 2005 Reviewer for NIH Macromolecular Structure and Function B Study Section 2006 Israel Science Foundation 2007 Editorial board member, the International Journal of Biological Chemistry

Awards and Honors: 1991 – 1993 Manitoba Health Research Council Studentship 1993 – 1994 Medical Research Council (MRC, Canada) Studentship 1994 – 1995 George H. Sellers Endowment Fund Postdoctoral Fellowship 1995 – 1998 MRC Postdoctoral Fellowship (terminated by awardee in 1996) 1996 – 1998 MRC/Pfizer Industrial Fellowship 1998 – 2000 California Tobacco Related Disease Research Program Fellowship 2002 UMDNJ nominee for Ellison Medical Foundation New Scholar Award

2003 RWJMS nominee for the Damon Runyon Cancer Research Foundation Scholar Award

B. Selected peer-reviewed publications (in chronological order) (an asterisk denotes corresponding author).

1. Fan, H., G. McClarty, R.C. Brunham. 1991. Biochemical Evidence for the existence of thymidylate synthase in the obligate intracellular parasite Chlamydia trachomatis. J. Bacteriol. 173, 6670-6677.

2. Fan, H., R.C. Brunham, G. McClarty. 1992. Acquisition and synthesis of folates by obligate intracellular bacteria of the genus Chlamydia. J. Clin. Invest. 90, 1803-1811.

3. McClarty, G., H. Fan, A.A. Andersen. 1993. Diversity in nucleotide acquisition by antigenically similar Chlamydia psittaci strains of avian origin. FEMS Microbiol. Lett. 108, 325-332.

4. McClarty, G., H. Fan. 1993. Purine metabolism by intracellular Chlamydia psittaci. J. Bacteriol. 175, 4662-4669.

5. Zhang, D.-J., H. Fan, G. McClarty, R.C. Brunham. 1995. Identification of the Chlamydia trachomatis RecA-encoding gene. Infect. Immun. 63, 676-680.

6. Fan, H., C. Villegas, J.A. Wright. 1996. Ribonucleotide reductase R2 component is a novel malignancy determinant that cooperates with activated oncogenes to determine transformation and malignant potential. Proc. Natl. Acad. Sci. USA. 93, 14036-14040.

7. Fan, H., C. Villegas, A. Huang, J.A. Wright. 1996. Suppression of malignancy by the 3' untranslated regions of ribonucleotide reductase R1 and R2 messenger RNAs. Cancer Res. 56, 4366-4369.

8. Fan, H., C. Villegas, J.A. Wright. 1996. A link between ferritin gene expression and ribonucleotide reductase R2 protein as demonstrated by retroviral vector-mediated stable expression of R2 cDNA. FEBS Lett. 382, 145-148.

9. Huang, A., H. Fan, J.A. Wright. 1997. Ribonucleotide reductase R2 protein expression and changes of drug resistance and genome stability. Cancer Res. 57, 4876-4881.

10. Fan, H., A. Huang, C. Villegas, J.A. Wright. 1997. The R1 component of mammalian ribonucleotide reductase has tumor suppressing activity as demonstrated by gene transfer experiments. Proc. Natl. Acad. Sci. USA. 94, 13181-13186.

11. Fan, H., C. Villegas, A. Chan, J.A. Wright. 1998. Myc epitope tagged proteins detected with the 9E10 antibody in immunofluorescence and immunopreciptation assays but not in Western blot analysis. Biochem. Cell Biol. 76, 125-128.

12. Fan, H., C. Villegas, J.A. Wright. 1998. The mammalian ribonucleotide reductase R2 component cooperates with a variety of oncogenes in mechanisms of cellular transformation. Cancer Res. 58, 1650-1653.

13. Fan, H., R. Derynck. 1999. Ectodomain shedding of TGF-α and other transmembrane proteins is induced by receptor tyrosine kinase activation and MAP kinase signaling cascades. EMBO J. 18, 6962-6972.

(Featured Science Magazine “paper of the week”: http://www.stke.org/cgi/content/full/OC_sigtrans;1999/13/tw1).

14. Shi, W., H. Fan, L. Shum, R. Derynck. 2000. The tetraspanin CD9 associates with transmembrane TGF-α and regulates TGF-α-induced EGFR activation and cell proliferation. J. Cell Biol. 148, 591-602.

15. Fan, H.*, C.W. Turck, R. Derynck. 2003. Characterization of growth factor-induced serine phosphorylation of tumor necrosis factor-α converting enzyme (TACE) and of an alternatively translated polypeptide. J. Biol. Chem. 278, 18617-18627.

16. Li, X., H. Fan*. 2004. Loss of ectodomain shedding due to mutations in the catalytic domain and cysteine-rich/disintegrin domain of the tumor necrosis factor-α converting enzyme (TACE). J. Biol. Chem. 279. 27365-27375.

http://www.stke.org/cgi/content/full/OC_sigtrans;1999/13/tw1

17. Zhang, Q., S. Xi, S. M. Thomas, M. J. Ogagan, J. M. Siegfried, H. Fan, T. E. Smithgall, J. Kamens, G. B. Mills, J. R. Grandis. 2006. Phosphorylation of TNF-α converting enzyme by gastrin-releasing peptide induces amphiregulin release and EGF receptor activation. Proc. Natl. Acad. Sci. USA. 103, 6901-6906.

18. Balakrishnan, A., B. Patel, S. Siebel, N. Pachikara, D. Chen, G. Zhong, B. Cravatt, H. Fan*. 2006. Matrix metalloprotease inhibitors GM6001 and TAPI-0 inhibit Chlamydia trachomatis by targeting polypeptide deformylase of the bacterium. J. Biol. Chem. 281:16691-16699.

19. Perez, L., J. E. Kerrigan, X. Li, H. Fan*. 2007. Substitution of methionine-435 in tumor necrosis factor-α converting enzyme with leucine, isoleucine and serine inactivate ectodomain shedding activity. Biochem. Cell Biol. 85:141-149.

20. Li, X., Perez, L., Z, Pan, H. Fan*. 2007. The transmembrane domain of TACE regulates protein ectodomain shedding. Cell Res. 17:985-998.

21. Pachikara, N., H. Zhang, Z. Pan, S. Jin, H. Fan*. 2009. Productive infection of Chlamydia trachomatis lymphogranuloma venereum 434 in cells with augmented or inactivated autophagy. FEMS Microbiology Letters. 292: 240-249.

22. Balakrishnan, A., L. Wang, X. Li, P. Ohman-Strickland, P. Malatesta, H. Fan*. 2009. Inhibition of chlamydial infection in the genital tract of female mice by topical application of a peptide deformylase inhibitor. Microbiol. Res. 164:338-346.

C. Research Support. List selected ongoing or completed (during the last three years) research projects (federal and non-federal support). Begin with the projects that are most relevant to the research proposed in this application. Briefly indicate the overall goals of the projects and your role (e.g. PI, Co-Investigator, Consultant) in the research project. Do not list award amounts or percent effort in projects.

Ongoing Research Support. 1. 4R33AI071954 (Fan) 09/01/2009 – 08/31/2012

NIH/NIAID Peptide Deformylase Inhibitor LBM415 for Sexually Transmitted Infections The major goal of this project is to continue preclinical evaluation LBM415 for the prevention of sexually transmitted chlamydial and gonococcal infections. Role: PI Total direct costs: $ 645,356

2. 1R03AG029859-01A1 (Fan) 07/01/2007 – 6/30/2010 NIH/NIA Role of Klotho Ectodomain Release in Suppression of Aging The major goals of this project are to identify the protease that release Klotho and to define the role Klotho ectodomain shedding in the regulation of aging. Role: PI Total direct costs: $ 100,000

3. 2R25GM055145-13 (Leibowitz) 03/13/2009 – 02/28/2013 NIH/NIGMS UMDNJ-RUTGERS UNIVERSITY PIPELINE PROGRAM Role: Key personnel

Completed Support: 1. 1R21AI071954-01A1 (Fan) 09/01/2007 – 08/31/2009

NIH/NIAID Peptide Deformylase Inhibitor LBM415 for Sexually Transmitted Infections The major goal of this project is to explore topical application of LBM415 for the prevention of sexually transmitted chlamydial and gonococcal infections.

Role: PI

Total direct costs: $ 275,000

2. 1 R21 AI64441 (FAN) 03/01/2005 – 02/28/2007 National Institute of Allergy and Infectious Diseases Specific Inhibition of Chlamydia with Hydroxamates The work supported by this grant led to the identification of chlamydial PDF as the target of hydroxamate-based metalloprotease inhibitors. Role: PI Total direct costs: $ 275,000

3. New Jersey Commission for Cancer Research 07/01/2006 – 06/31/2007 Control of TACE-mediated TGF-α Release in Cancer This grant contributed to the identification of catalytically inactive TACE mutants underlying ectodomain shedding-deficiencies in mutated CHO cell lines. Role: PI Total direct costs: $ 99,000

4. 2R01HL060061-06A2 (Schwarz) 04/01/2004 – 03/31/2008 NIH/NHLBI

EMAP II Regulation of Pulmonary Cell Proliferation Role: Consultant

1

BIOGRAPHICAL SKETCH

NAME

Zhaohui Feng eRA COMMONS USER NAME




Zhejiang University School of Medicine Hangzhou, China

M.D. 1988-1993 Clinical Medicine

Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China

Intern 1992-1993 Clinical Medicine

Zhejiang University School of Medicine Hangzhou, China

Ph.D. 1993-1998 Molecular Biology

New York University School of Medicine Tuxedo, New York

Postdoc 1998-2003 Environmental Medicine/Molecular Biology

Cancer Institute of New Jersey University of Medicine and Dentistry of New Jersey

Postdoc 2003-2007 Cancer Biology


Positions and Employement: 7/2007-6/2008 Instructor, Department of Pediatrics, University of Medicine and Dentistry of

New Jersey 7/2008-Present Assistant Professor (tenure-track), Department of Radiation Oncology/Division

of Cancer Biology, University of Medicine and Dentistry of New Jersey

B. Selected peer-reviewed publications

1. Feng Z, Hu W, Rom WN, Beland FA, Tang MS. (2002) N-hydroxy-4-aminobiphenyl-DNA binding in human p53 gene: sequence preference and the effect of C5 cytosine methylation. Biochemistry. 41:6414-6421.

2. Feng Z, Hu W, Rom WN, Beland FA, Tang MS. (2002) 4-aminobiphenyl is a major etiological agent of human bladder cancer: evidence from its DNA binding spectrum in human p53 gene. Carcinogenesis., 23:1721-1727.

3. Feng Z, Hu W, Komissarova E, Pao A, Hung MC, Adair GM, Tang MS. (2002) Transcription-coupled DNA repair is genomic context-dependent. J Biol Chem., 277:12777-12783.

4. Feng Z, Hu W, Chen JX, Pao A, Li H, Rom W, Hung MC, Tang MS. (2002) Preferential DNA damage and poor repair determine ras gene mutational hotspot in human cancer (see editorial). J Natl Cancer Inst., 94:1527-1536.

5. Hu W, Feng Z, Chasin LA, Tang MS. (2002) Transcription-coupled and transcription-independent repair of cyclobutane pyrimidine dimers in the dihydrofolate reductase gene. J Biol Chem., 277:38305-38310.

6. Feng Z, Hu W, Chasin LA, Tang MS. (2003) Effects of genomic context and chromatin structure on transcription-coupled and global genomic repair in mammalian cells. Nucleic Acids Res, 31:5897-5906.

7. Feng Z, Hu W, Amin S, Tang MS. (2003) Mutational spectrum and genotoxicity of the major lipid peroxidation product, trans-4-hydroxy-2-nonenal, induced DNA adducts in nucleotide excision repair-proficient and –deficient human cells. Biochemistry, 42:7848-7854.

8. Hu W, Feng Z, Tang MS. (2003) Preferential carcinogen-DNA adduct formation at codons 12 and 14 in the human K-ras gene and their possible mechanisms. Biochemistry, 42:10012-10023.

9. Feng Z, Hu W, Rom W, Costa M, Tang MS. (2003) Chromium(VI) exposure enhances polycyclic aromatic hydrocarbon-DNA binding at the p53 gene in human lung cells. Carcinogenesis, 24:771-778.

2

10. Zhang X, Succi J, Feng Z, Prithivirajsingh S, Story MD, Legerski RJ. (2004) Artemis is a phosphorylation target of ATM and ATR and is involved in the G2/M DNA damage checkpoint response. Mol Cell Biol., 24: 9207-9220.

11. Feng Z, Hu W, Tang MS. (2004) Trans-4-hydroxy-2-nonenal inhibits nucleotide excision repair in human cells: a possible mechanism for lipid peroxidation-induced carcinogenesis. Proc Natl Acad Sci U S A, 101:8598-8602.

12. Feng Z, Zhang H, Levine AJ, Jin S. (2005) The coordinate regulation of the p53 and mTOR pathways in cells. Proc Natl Acad Sci U S A, 102:8204-8209.

13. Feng Z, Hu W, Yu H, Tang MS (2006) Acrolein is a major cigarette-related lung cancer agent: preferential binding at p53 mutational hotspots and inhibition of DNA repair Proc Natl Acad Sci U S A, 103:15404-15409. (See comment in Proc Natl Acad Sci U S A. 2006, 103(43):15725-15726)

14. Levine AJ, Feng Z, Mak TW, You H, Jin S. (2006) Coordination and Communication between the p53 and IGF1-AKT-Tor signal transduction pathways. Genes Dev.,20:267-275.

15. Levine AJ, Hu W, Feng Z. (2006) The p53 pathway: what questions remain to be explored? Cell Death Differ. 13:1027-1036.

16. Feng Z, Jin S, Zupnick A, Hoh J, de Stanchina E, Lowe SW, Prives C, Levine AJ. (2006) p53 Tumor Suppressor Protein Regulates the Levels of Huntingtin Gene Expression. Oncogene, 25:1-7.

17. Levine AJ, Hu W, Feng Z, Gil G. (2007) Reconstructing Signal Transduction Pathways: Challenges and Opportunities. Ann N Y Acad Sci. 1115:32-50.

18. Hu W., Feng Z., Ma L., Wagner J., Rice JJ., Stolovitzky G., Levine, AJ. (2007) A single nucleotide polymorphism in the Mdm2 gene disrupts the oscillation of p53 and Mdm2 levels in cells. Cancer Res., 67(6):2757-65.

19. Feng Z., Hu W., de Stanchina E., Teresky AK., Jin S., Lowe S., Levine AJ. (2007) The regulation of AMPK β1, TSC2 and PTEN expression by p53: Stress, cell and tissue specificity and the role of these gene products in modulating the IGF-1-AKT-mTOR pathways. Cancer Res., 67(7):3043-53.

20. Feng Z, Hu W, Teresky AK, Hernando E, Cordon-Cardo C, Levine AJ. (2007) Declining p53 function in aging: a possible mechanism for high tumor incidence in older populations. Proc Natl Acad Sci USA., 104(42):16633-16638. (See comment in Proc Natl Acad Sci USA., 2007;104(47):18347-8)

21. Hu W., Feng Z (co-first author), Teresky AK., Levine AJ. (2007) p53 regulates maternal reproduction through LIF. Nature; 450 (7170): 721-724. (See comment in Nature, 450 (7170): 619)

22. Hu W, Feng Z, Atwal G, Levine AJ. (2008) p53: a new player in reproduction. Cell Cycle. 7(7):848-52. 23. Feng Z, Hu W, Rajagopal G, Levine AJ. (2008) The Tumor Suppressor p53; Cancer and Aging. Cell Cycle.

2008;7(7):842-7. 24. Kang H., Feng Z., Atwal G.S., Sun Y., Murphy M.E., Rebbeck T.R., Rosenwaks, Z., Levine, A.J. and Hu, W. (2009)

Single nucleotide polymorphisms in the p53 pathway regulate fertility in humans. Proc Natl Acad Sci USA., 106 (24): 9761-6.

25. Hu W, Feng Z, Levine AJ. (2009) The regulation of human reproduction by p53 and its pathway. Cell Cycle, 8(22):3621-2.

26. Feng Z. (2010) p53 Regulation of the IGF-1/AKT/mTOR Pathways and the Endosomal Compartment. The p53 family; Cold Spring Harb Perspect Biol;2:1-8. Cold Spring Harbor Laboratory Press

27. Hu W. Zhang C., Wu R., Sun Y. Levine A.J. Feng Z. GLS2, a novel p53 target gene, regulates energy metabolism and antioxidant function. (2010) Proc Natl Acad Sci USA., In press.

C. Rsearch Support Institutional seed award

a) The foundation of UMDNJ; b) The possible roles and mechanisms of GLS2, a novel p53 target gene, in energy metabolism; C) 2008-2009; D) $25,000; PI, 15% efforts

Institutional seed award a)The foundation of UMDNJ; b) The possible roles and mechanisms of leukemia inhibitory factor in breast cancer: c) 2009-2010; d) $25,000; PI, 15% efforts NJCCR seed grant

a) New Jersey Commission on Cancer Research (NJCCR); b) The role of LIF in breast cancer; C) 2009-2011; d) $270,189; PI, 15% efforts

NIH R01 grant a) NCI/NIH; b) The role of glutaminase 2, a novel p53 target gene in metabolism, in liver cancer; c) 2010 –2014; d)

$1,074,366; PI, 20% efforts

Foty, Ramsey A.

PHS 398/2590 (Rev. 09/04) Biographical Sketch Format Page 1


Follow this format for each person.

NAME Ramsey A. Foty, Ph.D. eRA COMMONS USER NAME fotyra




University of Toronto, Toronto, Canada B.Sc. 1982 Zoology University of Toronto, Toronto, Canada M.Sc. 1986 Dev. Biol. University of Toronto, Toronto, Canada Ph.D. 1991 Dev. Biol. Princeton University, Princeton, NJ Post Doc. Dev. Biol./Biophysics

A. Positions and Honors. Positions 1991-1993 NSERC Visiting Research Fellow, Dept. of Molecular Biology, Princeton University. 1993-1996 Research Associate, Department of Molecular Biology, Princeton University. 1996-1998 Professional Research Staff, Department of Molecular Biology, Princeton University 1998-1999 Instructor of Surgery, Department of Surgery, Division of Surgical Sciences, UMDNJ-RWJ Medical

School. 1999-2007 Assistant Professor of Surgery, Department of Surgery, Division of Surgical Sciences, UMDNJ-RWJ

Medical School. 2007- Associate Professor of Surgery, Department of Surgery, Division of Surgical Sciences, UMDNJ-RWJ

Medical School. Honors 1986 Pure and Applied Scientific Research Fellowship, University of Toronto. 1987 Life Sciences Committee Summer Research Award, University of Toronto. 1987/88 University of Toronto Open Fellowship. 1989/1990 Ontario Graduate Scholarship. 1991-1993 Natural Sciences and Engineering Research Council of Canada Post Doctoral Fellowship. 1996 International Society of Differentiation Fellowship. 1997 Gallo Award for Scientific Excellence in Cancer Research. The Cancer Institute of New Jersey. 1998 New Jersey Cancer Research Award. State of New Jersey Commission on Cancer Research. 2001-2002 American Foundation for Urologic Diseases Research Scholar B . Selected Publications Cowan, B.J., R.A. Foty and R.A. Liversage (1995). Insulin receptors in Xenopus laevis liver and the effects of local

insulin deprivation on forelimb regeneration. J. Exp. Zool. 273(1):130-141. Foty, R.A., C.M. Pfleger, G. Forgacs and M.S. Steinberg (1996). Surface tensions of embryonic tissues predict their

mutual envelopment behavior. Development 122(5):1611-1620. Steinberg, M.S. and R.A. Foty. (1997). Intercellular adhesions as determinants of tissue assembly and malignant

invasion. J. Cell. Physiol. 173: 135-139. Foty, Ramsey A. and Malcolm S. Steinberg (1997). Measurement of tumor cell cohesion and suppression of invasion by

E- or P-cadherin. Cancer Research 57:5033-5036. Forgacs, G., R.A. Foty, Y. Shafrir and M.S. Steinberg (1998). Viscoelastic properties of embryonic living tissues: a

quantitative study. Biophysical Journal 74:2227-2234.

Foty, Ramsey A.

Foty, R.A., S.A. Corbett, J.E. Schwarzbauer and M.S. Steinberg (1998). Effects of dexamethasone on cadherin-mediated cohesion of human fibrosarcoma HT-1080 cells. Cancer Research 58:3586-3589.

Ryan, P,L., R.A. Foty, J. Kohn and M.S. Steinberg (2001). Tissue spreading on implantable substrates is a competitive

outcome of cell-cell vs. cell-substratum adhesivity. PNAS 98(8):4323-4327. Robinson, E., Zazzali, K., Corbertt, S. and Foty, R. (2003). α5β1 integrin mediates strong tissue cohesion. Journal of

Cell Science 116(2):377-386. Duguay, D., Foty, R.A. and Steinberg, M.S. (2003). Qualititative and quantitative determinants of cadherin-mediated cell

sorting. Developmental Biology 253:309-323. Robinson, E., Foty, R. and Corbertt, S. (2004). Fibronectin matrix assembly regulates α5β1 integrin mediated cell

cohesion. Mol. Biol. Cell 15:973-981. Forgacs, G. and R. Foty (2004). Biological relevance of tissue liquidity and viscoelasticity. Function and regulation of

cellular systems: Experiments and models, 269-277. Foty, Ramsey A. and Malcolm S. Steinberg (2004). Cadherin-mediated cell-cell adhesion and tissue segregation in

relation to malignancy. Int. J. Dev. Biol. 48:397-409. Winters, B.S., Scott R. Shepard and Ramsey A. Foty (2005). Biophysical measurement of brain tumor cohesion. Int. J.

Cancer 114:371-379.

Foty, Ramsey A. and Malcolm S. Steinberg (2005). The Differential Adhesion Hypothesis: a direct evaluation. Dev. Biol. 278(1):255-263.

Yang. J-M, P. O’Neill, W. Jin, R. Foty, D.J. Medina, Z. Xu, M. Lomas, G.M. Arndt, Y. Tang, M. Nakada, L. Yan, and W.N.

Hait (2006). EMMPRIN (CD147) confers resistance of breast cancer cells to anoikis through inhibition of BIM. J. Biol. Chem. 281(14):9719-9727.

Winters, B.S., B.K. Mohan Raj, E.E. Robinson, R.A. Foty, and S.A. Corbett (2006). Three-dimensional culture regulates Raf-1 expression to modulate fibronectin matrix assembly. Mol. Bio. Cell 17:3386-3396.

Perez-Pomares, J.M. and R. A. Foty (2006). Tissue fusion and cell sorting in embryonic development and disease: biomedical implications. Bioessays 28:809-821.

Jia, Dongxuan, Daniel DaJusta, and Ramsey A. Foty (2007). Tissue surface tensions guide in vitro self-assembly of

rodent pancreatic islets. Dev. Dyn. 236(8):2039-2049. Schötz, Eva-Maria, Rebecca D. Burdine, Frank Julicher, Malcolm S. Steinberg, Carl-Philipp Heisenberg, and Ramsey A. Foty (2008). The role of differential adhesion in zebrafish germ layer

positioning. HFSP Journal 2(1):42-56. Shinbrot,T.,Caicedo-Carvajal,C, and R.A. Foty (2009). Cellular morphogenesis in silico. Biophys. J. (in press).

Current Support: 1R01CA118755-01 09.01/2008-07/31/2013 6.0 calendar NIH/NCI $1,612,922 PI Tumor microenvironment, tissue liquidity and cell interactions in prostate cancer. Goals: This project explores the role of tumor biomechanical properties in promoting invasion and how changes in cell-ECM interactions contribute to the process. Overlap: None.

PHS 398/2590 (Rev. 09/04) Continuation Format Page



NAME Gabriel, Abram eRA COMMONS USER NAME agabriel1

POSITION TITLE Associate Professor of Molecular Biology and Biochemistry


INSTITUTION AND LOCATION DEGREE

(if applicable)

YEAR(s) FIELD OF STUDY

Harvard College, Cambridge MA BA 1977 Biochemistry Johns Hopkins School of Medicine, Baltimore MD MD 1982 Medicince Johns Hopkins School of Public Health, Balt. MD MPH 1982 Public Health

A. Positions and Honors. Positions and Employment 1982 - 1985 Intern, Assistant, and Senior Assistant Resident, Department of Pediatrics, Johns

Hopkins Hospital 1985 - 1987 Postdoctoral Fellow, Department of Biological Chemistry, Johns Hopkins University

School of Medicine (Advisor: Dr. Don Cleveland) 1987 - 1989 Research Associate, Department of Biological Chemistry, Johns Hopkins

University School of Medicine (Advisor: Dr. Don Cleveland) 1989 - 1992 Research Associate, Department of Molecular Biology and Genetics, Johns

Hopkins University School of Medicine (Advisor: Dr. Jef Boeke) 1992 - 1999 Assistant Professor, Department of Molecular Biology and Biochemistry,

Rutgers University 1997 – present Member, Cancer Institute of New Jersey 1999 - present Associate Professor, Department of Molecular Biology and Biochemistry,

Rutgers University 2001 – present Acting Director, Rutgers/UMDNJ Joint Graduate Program in Biochemistry 2009 – present Representative, Rutgers University Senate Honors and Relevant Experiences 1974 National Merit Scholarship 1978 Howard Hughes Summer Research Fellowship, 1978 1987 - 1991 Physician Scientist Award, National Institute of Allergy and Infectious Disease 1991 - 1997 Lucille P. Markey Scholar Award in Biomedical Science 1999 – 2001 Isermann Family Foundation Cancer Research Award 2001 US Pat. No. 6,183,969, for "Intron-based assay for detecting and characterizing chromosomal rearrangement" 2003 Scientific Planning Committee, 4th Colmar Scientific Symposium, Colmar, France 2007 US Pat. No. 7,264,931, for “A method for sequencing nucleic acid sequences without chain termination”

B. Selected peer-reviewed publications. Starfield,B., Katz, H., Gabriel, A., Livingston, G., Benson, P., Hankin, J., Horn, S., and Steinwachs, D. Morbidity in Childhood: A Longitudinal View. New England Journal of Medicine, 310, 824, 1984. Mathias, S., Scott, A., Kazazian, H., Boeke, J.D. and Gabriel, A. Reverse transcriptase encoded by a human transposable element. Science, 254, 1808, 1991. Teng, S.C., Kim, B., and Gabriel, A. Retrotransposon reverse transcriptase-mediated repair of chromosomal breaks in Saccharomyces cerevisiae, Nature, 383, 641-644, 1996. Sassaman, D.M., Dombroski, B.A., Moran, J.V., Kimberland, M.L., Naas, T.P., DeBerardinis, R.J., Gabriel, A., Swergold, G.D., and Kazazian, H.H. Many human L1 elements are capable of retrotransposition, Nature Genetics, 16, 37-43, 1997. Kim, J.M., Vanguri, S., Boeke, J.D., Gabriel, A., and Voytas, D.F. Transposable elements and genome organization: a comprehensive survey of retrotransposons revealed by the complete Saccharomyces cerevisiae genome sequence, Genome Research, 8, 464-478, 1998. Yu, X. and Gabriel, A. Patching broken chromosomes with extranuclear cellular DNA, Molecular Cell, 4, 873-881, 1999. Kim, D.Y., Kim, T.Y., Walsh, T. Kobayashi, Y., Matise, T., Buyske, S., and Gabriel, A. Widespread RNA editing of embedded Alu elements in the human transcriptome, Genome Research, 14,1719-1725, 2004. Gabriel, A., Dapprich J., Kunkel, M., Gresham, D., Pratt, S., and Dunham, M. Global Mapping of Transposon Location, PLoS Genetics, 2, e212, 2006. Tseng, S-F., Gabriel, A. and Teng, S-C. Proofreading activity of DNA polymerase Pol2 mediates 3’-end processing during nonhomologous end joining in yeast, PLoS Genetics, 4(4), e1000060, 2008. Harris, C., DeWan, A., Zupnick, A., Normart, R., Gabriel, A., J. Prives, C., Levine, A.J. and Hoh, J. p53 responsive elements in human L1 retrotransposons, Oncogene, 28, 3857-3865, 2009. Gabriel, A. A Biologist’s Perspective of DNA and Race in the Genomics Era, in Genetics and the Unsettled Past: The Collision of DNA, Race and History, eds. Bay, M., Lee, C., Nelson, A., and Wailoo, K., in press (Rutgers University Press, Studies in Race and Ethnicity) Gabriel, A. and Przybylski, J. Sickle-cell anemia: A Look at Global Haplotype Distribution. Nature Education 3(3):2, 2010. C. Research Support 2005 – 2008 Cancer Institute of New Jersey Collaborative Grant, Gabriel (PI) Retrotransposons and p53 in Cancer Genomic Instability ($40,000) This study examined an unexpected link between p53 and human LINE element activity.

PI: Gartenberg, Marc

BIOGRAPHICAL SKETCH

NAME Gartenberg, Marc R.


INSTITUTION AND LOCATION DEGREE YEAR(s) FIELD OF STUDY

University of California, Berkeley B.Sc. 1981-5 Chemistry Yale University Ph.D. 1985-90 Chemistry Harvard University Post-doc 1990-93 Mol. Biol.

A. Positions and Honors:

Positions 1993 to 2000 – Asst. Prof., Department of Pharmacology, Robert Wood Johnson Medical School 2000 to 2005 – Assoc. Prof., Department of Pharmacology, Robert Wood Johnson Medical School 2005 to present – Prof., Department of Pharmacology, Robert Wood Johnson Medical School 2002 – Visiting Prof., University of Geneva, Dept. of Mol. Biol., Geneva, Switzerland 2002 to present – Director, Graduate Program in Cellular and Molecular Pharmacology, University of Medicine and Dentistry of New Jersey – Robert Wood Johnson Medical School (UMDNJ-RWJMS) 2007 to 2010 – Permanent member, NIH MGC study section

Academic Appointments (Faculty Member) Joint Graduate Programs in Pharmacology, Microbiology and Biochemistry at UMDNJ-RWJMS and Rutgers Univ. Graduate Program in Molecular Biophysics at Rutgers University Cancer Institute of New Jersey Department of Biochemistry, Division of Nucleic Acids Enzymology, UMDNJ-RWJMS

B. Publications (* indicates corresponding author)

1) Liu-Johnson, H.-N., Gartenberg, M.R. and Crothers, D.M.* (1986). The DNA Binding Domain and Bend Angle of E. coli CAP Protein. Cell 47, 995-1005. 2) Gartenberg, M.R. and Crothers, D.M.* (1988). DNA Sequence Determinants of CAP-induced Bending and Protein Binding Affinity. Nature 333, 824-9. 3) Dalma-Weishausz, D.D., Gartenberg, M.R. and Crothers, D.M.* (1990). Sequence-dependent contribution of the distal binding domains to CAP protein-DNA binding affinity. Nucl. Acids Res. 19, 611-6. 4) Gartenberg, M.R., Ampe, C., Steitz, T.A. and Crothers, D.M.* (1990). Molecular Characterization of the GCN4-DNA Complex. PNAS 87, 6034-8. 5) Gartenberg, M.R. and Crothers, D.M.* (1991). Synthetic DNA bending sequences increase the rate of in vitro transcription initiation at the E. coli lac promoter. J. Mol. Biol. 219, 217-30. 6) Crothers, D.M.*, Gartenberg, M.R. and Shrader, T.E. (1991). DNA bending in protein-DNA complexes. Methods Enzymol. 208, 118-46. 7) Gartenberg, M.R. and Wang J.C.* (1992). Positive Supercoiling Greatly Diminishes mRNA Transcription in Yeast. PNAS 89, 11461-5.

8) Roca, J., Gartenberg, M.R., Oshima, Y. and Wang, J.C.* (1992). A hit-and-run system for targeted genetic manipulations in yeast. Nucl. Acids Res. 20, 4671-2. 9) Gartenberg, M.R. and Wang, J.C.* (1993). Identification of Barriers to Rotation of DNA Segments in Yeast from the Topology of DNA Rings Excised by an Inducible Site-specific Recombinase. PNAS 90, 10514-8. 10) Mirabella, A. and Gartenberg, M.R.* (1997). Yeast Telomeric Sequences Function as Chromosomal Anchorage Points in vivo. EMBO J. 16, 523-33. 11) Ansari, A. and Gartenberg, M.R.* (1997). The yeast silent information regulator Sir4p anchors and partitions plasmids. Mol. Cell Biol. 17, 7061-8. 12) Tsalik, E.T. and Gartenberg, M.R.* (1998). Curing Saccharomyces cerevisiae of the 2 micron plasmid by targeted DNA damage. Yeast 14, 847-52. 13) Cheng, T.-H., Li, Y.-C., and Gartenberg, M.R.* (1998). Persistence of an Alternate Chromatin Structure at Silenced Loci in the Absence of Silencers. PNAS 95, 5521-6. 14) Ansari, A. and Gartenberg, M.R.* (1999). Persistence of Silent Chromatin Structure in vitro. PNAS 96, 343-8.

15) Ansari, A., Cheng, T.-H., and Gartenberg, M.R.* (1999). Isolation of selected chromatin fragments from yeast by site-specific recombination in vivo. Methods, A Companion to Methods in Enzymology 17, 104-11. 16) Gartenberg, M.R.* (1999). Formation of extrachromosomal DNA rings in Saccharomyces cerevisiae. In Protocols for DNA Topoisomerases, v. I, pgs 125-134, eds. Bjornsti, M. and Osheroff, N., (Humana Press, NJ). 17) Cheng, T.-H. and Gartenberg, M.R.* (2000). Maintenance of Yeast Heterochromatin is a Dynamic Process that Requires Silencers Continuously. Genes Dev. 14, 452-63. 18) Edwards, T.K., Saleem, A., Shaman, J.A., Dennis, T., Gerigk, C., Oliveros, E., Gartenberg, M. R., Rubin, E. H.* (2000). Role for nucleolin/Nsr1 in the cellular localization of topoisomerase I. J. Biol. Chem. 275, 36181-8. 19) Gartenberg, M.R.* (2000). The Sir proteins of Saccharomyces cerevisiae: mediators of transcriptional silencing and much more. Curr. Opin. Microbiol. 3, 132-137. 20) Cheng, T.-H., Chang, C.-R., Joy, P., Yablok, S., and Gartenberg, M.R.* (2000). Controlling Gene Expression in Yeast by Inducible Site-Specific Recombination. Nucl. Acids Res. 28, e108 (pgs 1-6). 21) Li, Y.-C., Cheng, T.-H., and Gartenberg, M.R.* (2001). Establishment of Transcriptional Silencing in the Absence of DNA Replication. Science 291, 650-3. 22) Andrulis, E.A., Zappulla, D.C., Ansari, A.I., Perrod, S., Laiosa, C.V., Gartenberg, M.R.,* and Sternglanz, R.* (2002). Esc1, a Nuclear Periphery Protein Required for Sir4-based Plasmid Anchoring and Partitioning. Mol. Cell. Biol. 22, 8292-301. 23) Gartenberg, M.R.,* Laroche, T., Blaszczyk, M and Gasser, S.M. (2004). Sir-mediated Repression Can Occur Independently of Chromosomal and Subnuclear Contexts. Cell 119, 955-67. 24) Gasser, S.M.,* Hediger, F., Taddei, A., Neumann, F.N., and Gartenberg, M.R. (2004). The Function of Telomere Clustering in Yeast: the Circe Effect. In Epigenetics, Cold Spring Harbor Symposia on Quantitative Biology, vol. 69. eds. B. Stillman and D. Stewart. New York, Cold Spring Harbor laboratory Press, 327-38. 25) Taddei, A., Gartenberg, M.R., Neumann, F.R., Hediger, F., and Gasser, S.M.* (2005). Multiple Pathways Tether Telomeres and Silent Chromatin at the Nuclear Periphery: Functional Implications for Sir-Mediated Repression. In

Nuclear Organization in Development and Disease, eds. C. Stewart and B. Goldman. Chichester, Wiley.A Novartis Foundation Symposium, 264, 140-56. 26) Chang, C.-R., Wu, C.-S., Hom, Y., and Gartenberg, M.R.* (2005). Targeting of Cohesin by Transcriptionally Silent Chromatin. Genes Dev. 19, 3031-42. 27) Mead, J., McCord, R., Youngster, L., Sharma, M., Gartenberg, Marc R. and Vershon, A.K.* (2007). Interconversion between Localized and Regional Silencing Mechanisms by Modulating Hst1 and Sir2 Deacetylase Binding Partner Specificity. Mol. Cell Biol. 27, 2466-75. 28) Dubey, R.D. and Gartenberg, M.R.* (2007). A tDNA Establishes Cohesion of a Neighboring Silent Chromatin Domain. Genes Dev. 21, 2150-60. 29) Valenzuela, L., Dhillon, N., Dubey, R.N., Gartenberg, M.R. and Kamakaka, R.T.* (2008). Long-range Communication between the Silencers of HMR. Mol. Cell Biol. 28, 1924-35. 30) Schober, H. Kalck, V., Vega-Palas, M.A., Van Houwe, G., Sage, D., Unser, M., Gartenberg, M.R., and Gasser, S.M.* (2008). Controlled exchange of chromosomal arms reveals principles driving telomere interactions in yeast. Genome Research 18, 261-71. 31) Chou, C.-C, Li, Y.-C. and Gartenberg, M.R.* (2008). Bypassing Sir2 and O-acetyl-ADP-ribose in Transcriptional Silencing. Mol. Cell 31, 650-59. 32) Gartenberg, M.R.* and Merkenschlager, M.* (2008). Condensin goes with the family but not with the flow. Genome Biology 9, 236 (pgs 1-3). 33) Gartenberg, M.R.* (2009). Heterochromatin and the cohesion of sister chromatids. Chromosome Res. 17, 229-38 34) Gartenberge, M.R.* (2009). Life on the edge: telomeres and persistent double strand breaks converge at the nuclear envelope. Genes Dev. 23, 1027-31. 35) Wu, C.-S, Chen, Y.-F. and Gartenberg, M. R.* (2010). Targeted Sister Chromatid Cohesion by Sir2 in Budding Yeast. Manuscript in preparation.

C. Current Support Active Chromosome Architecture: Cohesion of Transcriptionally Silenced Domains (USPHS 2R01GM51402). I am currently in my 16th year of continuous funding. This is the third year of a four-year cycle (scoring in the 5.9 percentile). The long-term goals of this project are to elucidate the mechanisms and consequences of heterochromatic cohesion. Specific objectives include determining the roles of Sir proteins and RNA pol III components in cohesin recruitment and how cohesin functions once it has been targeted to silenced domains. Role – Principle Investigator Establishment Of Sister Chromatid Cohesion In Heterochromatin (March of Dimes, 1-FY08-481). The long-term goals of this grant are to determine the roles of retrotransposon sequences in cohesin recruitment and to determine how the complex, once recruited, moves between sites on DNA. We will also examine the mode of cohesin binding to a variety of non-silenced sites to determine how they compare to binding within silenced chromosomal domains. Role – Principle Investigator

PI: Gartenberg, M. R.

Support Title – Chromosome Architecture: Cohesion of Transcriptionally Silenced Domains Granting Agency – USPHS Grant number – 2R01GM51402 Role – PI Direct – $1,180,620 over four years Period – 2007 to 2011 Percent effort – 50% Title – Establishment of Sister Chromatid Cohesion in Heterochromatin Granting Agency – March of Dimes Grant Number – 1-FY08-481 Role – PI Direct – $300,000 over three years Period – 2008 to 2010 Percent effort – 25% Title – Impact of Benzene Metabolites on Chromosome Condensation in Yeast Granting Agency – American Petroleum Institute Role – PI Direct – $75,000 over two years Period – 2008 to 2009 Percent effort – 20%



NAME

Gélinas, Céline eRA COMMONS USER NAME

Gelinas

POSITION TITLE

Professor



Université de Sherbrooke, Québec. Canada B.Sc. 1981 Chemistry/Biochemistry Université de Sherbrooke, Québec. Canada Ph.D. 1985 Microbiol./Tumor Virol. (Marcel F. Bastin) University of Wisconsin, Madison, WI Postdoc 1985-1988 Oncogenic Retroviruses McArdle Laboratory for Cancer Research (Howard M. Temin)

A. Positions and Honors

Research, Teaching, and Professional Experience: 1988-1994 Assistant Professor, University of Medicine and Dentistry of New Jersey (UMDNJ)–Robert

Wood Johnson Medical School (RWJMS), Dept. Biochemistry 1988-present Resident Faculty Member, Center for Advanced Biotechnology and Medicine

1988-present Member, Graduate Program, Biochemistry and Molecular Biology, RWJMS 1989-present Member, Graduate Program, Microbiology and Molecular Genetics, Rutgers Univ. 1994-2000 Associate Professor UMDNJ - Robert Wood Johnson Med. Sch., Dept. Biochemistry 1995-present Member, Cancer Institute of New Jersey 1997-present Member, Graduate Program, Molecular Genetics and Microbiology, RWJMS 2000-present Professor, UMDNJ - Robert Wood Johnson Medical School, Dept. Biochemistry 2004-present Member, Joint Graduate Program in Cellular & Molecular Pharmacology, Rutgers/UMDNJ 2008-present Associate Dean for Research, UMDNJ - Robert Wood Johnson Medical School Editorial Board Member: 1995-2001 Archives of Biochemistry and Biophysics Reviewer for: Molecular Cell, Genes & Development, EMBO Journal, EMBO Reports, Journal of Clinical Investigation, Journal of Cell Biology, Proceedings of the National Academy of Sciences USA, Molecular and Cellular Biology, The Journal of Biological Chemistry, Oncogene, Journal of Virology, Cancer Research, Virology, Cell Growth & Differentiation, Nucleic Acids Research, Leukemia Research, Journal of Cellular Biochemistry, Gene, Toxicologic Pathology, Cancer Letters, Molecular Cancer Therapeutics Honors and Awards: 1981-84 National Cancer Institute of Canada Graduate Student Fellowship 1981-84 FCAC (Québec's Government) Graduate Student Fellowship 1981 Medical Research Council of Canada Graduate Student Fellowship (declined) 1981 Fernand Seguin Award for Academic Excellence, Université de Sherbrooke 1983 Medical Research Council of Canada Graduate Student Fellowship (declined) 1983 Boehringer-Mannheim Canada First Graduate Student Prize, Canadian Biochemical Society 1984 Jean-Marie Beauregard Award for Academic and Research Excellence 1985-87 National Cancer Institute of Canada King George V Silver Jubilee Postdoctoral Fellowship 1985 Medical Research Council of Canada Postdoctoral Fellowship (declined) 1985 FCAC (Québec's Government) Postdoctoral Fellowship (declined) 1987-88 Medical Research Council of Canada Postdoctoral Fellowship 1990-93 Basil O'Connor Starter Scholar Research Award March of Dimes Birth Defect Foundation 1995 NJ Commission on Cancer Research Award for Outstanding Service to Cancer Research 1999 Reviewer, NIH Program Project Site Visit (P01), Kimmel Cancer Ctr, Thomas Jefferson U. 2001 Ad Hoc member - NIH Molecular Biology Study Section (CDF-1) 2001 Session Chair – Seventeenth Annual Meeting on Oncogenes, Frederick, MD

2002 Session Chair – Keystone Meeting on NF-kB, Keystone, CO 2002 Reviewer, NIH – NCI Program Project Grant (P01), The Burnham Institute, La Jolla 2002 Ad Hoc - NIH Special Emphasis Panel Molecular Biology Study Section ZRG1 CDF-1 01 2002 Ad Hoc member - NIH Experimental Virology Study Section (EVR) 2003-04 Member, NIH Experimental Virology Study Section (EVR) 2004-07 Member, NIH Virology B Study Section (VIRB) 2006 Master Educator, UMDNJ Stuart D. Cook Master Educators Guild 2007 Reviewer, NIH – NIEHS Program Project Grant (P01), Boston Univ. School of Medicine 2009 The Leukemia and Lymphoma Society Tom Bell and Jennifer Bell-Keating Research Grant 2010-pres Member, NIH College of CSR Reviewers 2010 Elected to Fellowship in the American Academy of Microbiology B. Selected publications (in chronological order) from 59

Gélinas, C. and White, E. (2005) BH3-only proteins in control: specificity regulates MCL-1 and BAK-mediated apoptosis. Genes & Dev. 19: 1263-1268.

Kucharczak, J.F., Simmons, M.J., Duckett, C.S. and Gélinas, C. (2005) Constitutive proteasome-mediated turnover of Bfl-1/A1 and its processing in response to TNF receptor activation in FL5.12 pro-B cells convert it into a pro-death factor. Cell Death & Differ. 12: 1225-1239.

Fan Y, Dutta J, Gupta N, Gélinas C. (2006) Molecular Basis of Oncogenesis by NF-kB: From a bird¹s eye view to a relevant role in cancer. In: Liou H-C, ed. in NF-kB/Rel Transcription Factor Family. Georgetown: Landes Bioscience/Eurekah.com, New York: Springer Science +Business Media,pp 112-130.

Degenhardt K, Mathew R, Beaudoin B, Bray K, Anderson A, Chen G, Mukherjee C, Shi Y, Gélinas C, Fan Y, Nelson D, Jin S and White E. (2006) Autophagy promotes tumor cell survival and restricts necrosis, inflammation and tumorigenesis. Cancer Cell 10: 51-64.

Pegman, P.M., Smith, S.M., D'Souza, B.N., Loughran, S.T., Maier, S, Kempkes, B., Cahill, P.A., Simmons, M.J., Gélinas, C. and Walls, D.. (2006) The Epstein-Barr virus nuclear antigen 2 trans-activates the cellular anti-apoptotic bfl-1 gene by a CBF-1/RBPJk dependent pathway. J. Virol. 80: 8133-8144.

Dutta J, Fan, Y, Gupta N, Fan G and Gélinas C. (2006) Current insights into the regulation of programmed cell death by NF-kB. Oncogene 25: 6800-6816.

Liu A, Li, J, Marin-Husstege, M, Kageyama R, Fan Y, Gélinas, C and Casaccia-Bonnefil, P (2006) A molecular insight of Hes5-dependent inhibition of myelin gene expression: old partners and new players. EMBO J. 25: 4833-4842.

Fan Y, Gélinas C (2007) An optimal range of transcription potency is necessary for efficient cell transformation by c-Rel to ensure optimal nuclear localization and gene-specific activation Oncogene 26: 4038-4043.

Fan, Y, Dutta J, Gupta N, Fan G and Gélinas C. (2008) Regulation of programmed cell death by NF-KB and its role in tumorigenesis and therapy. Adv Exp Med Biol. 615: 223-50.

Gupta N, Delrow J, Drawid, A, Sengupta AM, Fan G and Gélinas C. (2008) Repression of BLNK and BCAP is important for lymphocyte transformation by Rel proteins. Cancer Research 68: 808-814.

Simmons, M.J, Fan G, Zong, W.X., Degenhardt K, White E and Gélinas C. (2008) Bfl-1/A1 functions, similar to Mcl-1, as a selective tBid and Bak antagonist. Oncogene 27: 1421-1428.

Dutta J, Fan G and Gélinas C. (2008) CAPERα is a novel Rel-TAD-interacting factor that inhibits lymphocyte transformation by the potent Rel/NF-κB oncoprotein v-Rel. J. Virol. 82: 10792-10802..

Fan G, Fan Y, Gupta N, Matsuura I, Liu F, Zhen Zhou X, Lu KP and Gélinas C. (2009) Peptidyl-prolyl isomerase Pin1 markedly enhances the oncogenic activity of the Rel proteins in the NF-κB family.. Cancer Research 69: 4589-4597.

Mathew R, Karp C, Beaudoin B, Vuong N, Chen G, Chen H-Y, Bray K, Reddy A, Bhanot G, Gelinas C, DiPaola RS, Karantza-Wadsworth V, White E. (2009) Autophagy suppresses tumorigenesis through elimination of p62. Cell 137: 1062-1075.

Drawid A, Gupta N, Nagaraj VH, Gélinas C and Sengupta A. (2009) A Hidden Markov Model with position-dependent transition probabilities accurately predicts the occupancy of a transcription factor on self-overlapping binding motifs. BMC Bioinformatics 10: 208-234.

Fan G, Simmons MJ, Ge S, Dutta-Simmons J, Kucharczak J, Ron Y, Weissmann D, Chen CC, Mukherjee C, White E and Gélinas C. (2010) Defective ubiquitin-mediated degradation of anti-apoptotic Bfl-1 predisposes to lymphoma. Blood, in press. Feb 25. [Epub ahead of print]

C. Research Support. ACTIVE R01 CA083937-07 (Gélinas) 06/05/08 - 03/31/11 NIH/NCI $486,675 (direct costs) Functional analysis of Bfl-1/A1 in apoptosis and oncogenesis The goals are to determine the mechanisms that control ubiquitination of apoptosis inhibitor Bfl-1/A1 and its role in regulating Bfl-1’s role in tumorigenesis and chemoresistance. Role: PI 6138-09 (Gélinas) 10/01/08 – 09/30/11 The Leukemia and Lymphoma Society $540,000 (direct costs) Tom Bell and Jennifer Bell-Keating Translational Research Grant Bfl-1 as a Therapeutic Target and Prognostic Indicator in B-CLL and AML The goals are to determine if Bfl-1 is a potential therapeutic target for B-CLL and AML and to identify and characterize Bfl-1 variants in drug-resistant B-CLL and AML. Role: PI W81XWH-09-1-0598 (Molli) 08/15/09 – 08/14/12 Department of Defense $225,000 (direct costs) Breast Cancer Research Program Post-doctoral Award Tumor suppressor role of CAPERα in ERα negative and Rel/NF-kB-positive breast cancer The goal of this project to study the tumor suppressor activity of CAPER in breast cancer and its impact on NF-kB activity is an exciting area of research with great potential, particularly as it relates to understanding the mechanisms involved in the progression to invasive breast cancer. Role: Sponsor/Mentor 09-1083-CCR-E0 (White) 06/26/09 - 06/25/10 New Jersey Commission on Cancer Research Development Award $500,000 (direct costs) Multidisciplinary research network targeting the autophagy pathway for cancer therapy The goals of this multi-disciplinary collaborative grant (4 projects) are to define the molecular mechanisms governing autophagy and to modulate the autophagy pathway to develop novel approaches to cancer therapy. Role: co-PI W81XWH06-1-0514 (White) Department of Defense Prostate Cancer Research Program 10/01/07 – 08/31/10 (no cost extension) CINJ Interdisciplinary Cancer Research Grant $110,000 (direct costs) Regulation of cell death in oncogenesis and therapy The goals of this pilot project (1 of 5) are to investigate the roles of deficiency in different cell death pathways and its interplay with NF-kB in cancer and therapy. Role: co-PI COMPLETED (last 3 years) R01 CA054999-15 (Gélinas) 07/01/91-06/30/06 NIH/NCI (no cost extension to 06/30/07) Trans-acting function of the v-and c-Rel oncoproteins The goals were to study how the transactivation function of Rel proteins affects cell survival, proliferation and oncogenesis, to characterize its mode of action and to explore the role of phosphorylation in its regulation. Role: PI 07-1057-CCR-E0 (Gélinas) 07/01/06 - 06/30/08 New Jersey Commission on Cancer Research (no cost-extension to 6/30/09) Role of CAPERα in ER and NF-κB activity in breast cancer The goal of this grant is to develop an inducible shRNA system to study the role of CAPERα interaction with Rel/NF-kB proteins and ER in breast cancer cells.

Role: PI Foundation of UMDNJ (Gelinas) 10/01/07 - 9/30/08 Functional analysis of Bfl-1/A1 in apoptosis and oncogenesis $25,000 (direct costs) The goal of this bridging grant was to gather necessary data to secure renewal of NIH grant R01 CA083937. Role: PI





NAME Glod, John eRA COMMONS USER NAME (credential, e.g., agency login) JohnGlod

POSITION TITLE Assistant Professor of Pediatrics & Pharmacology



Lehigh University Bethlehem, PA

BS 1988 Biochemistry

University of Colorado Health Sciences Center, Denver, CO

MD / PhD 1996 PhD in Pharmacology

Children’s Hospital Medical Center, Cincinnati (CHMCC)

Residency 1996-1999 Pediatrics

CHMCC Fellowship 1999-2000 Peds Heme/Onc NCI / Johns Hopkins NCI / Johns Hopkins

Fellowship Fellowship

2000-2002 2002-2003

Peds Heme/Onc Neuro-Oncology

Please refer to the application instructions in order to complete sections A, B, and C of the Biographical Sketch. A. Positions and Honors. Positions and Employment 2003- Assistant Professor of Pediatrics, UMDNJ / Robert Wood Johnson Medical School, New Brunswick, NJ

2007- Assistant Professor of Pharmacology, UMDNJ / RWJMS, New Brunswick, NJ 2007- Director, Scientific Review Board, The Cancer Institute of New Jersey Other Experience and Professional Memberships 2004- Member, Children’s Oncology Group 2004- Member, The American Society of Pediatric Hematology/Oncology 2004- Member, The Cancer Institute of New Jersey 2005-2006 Co-chair, Neuro-oncology Committee, CINJ oncology group,

Honors 1990- Department of Radiology Student Research Award 1990- Glaxo award for outstanding pharmacology graduate student 1995- Junior Alpha Omega Alpha, Medical Honor Society

B. Selected peer-reviewed publications (in chronological order).

1. Jones, D.A., Glod, J., Wilson-Shaw, D., Hahn, W.E., and Sikela, J.M. (1991) cDNA Sequence and Differential Expression of the Mouse Ca2+/Calmodulin-dependent Protein Kinase IV Gene. FEBS Lett. 289(1): 105-9. 2. Tokumitsu, H., Brickey, D.A., Glod, J., Sikela, J.M., and Soderling, T.R., (1994) Activation Mechanisms for Ca2+/Calmodulin-dependent Protein Kinase Type IV. Identification of a Brain CaM Kinase IV Kinase. J.Biol.Chem. 269(46): 28640-7. 3. Cohen, KJ, Broniscer, A., and Glod, J. (2001) Pediatric Glial Tumors. Current Treatment Options in Oncology 2:529-536. 4. Glod, J. , Koch, B., Myseros, J., Breneman, J., and Collins, M. H., (2002) Issues Concerning the Treatment of a Child With Craniopharyngioma. Med. Ped Oncology 38:360-367


PHS 398/2590 (Rev. 11/07) Page

5. Ferrari, N, Glod, J*., Lee, J., Kobiler, D., and Fine H.A., (2003) Bone Marrow-derived, Endothelial Progenitor-like Cells as Angiogenesis-Selective Gene Targeting Vectors. Gene Therapy 10(8):647-56. * the first two authors contributed equally to the manuscript

6. Anderson, SA, Glod, J, Arbab, AS, Noel, M, Ashari, P, Fine, HA, and Frank, JA., (2005) Non-Invasive MR Imaging of Magnetically Labeled Stem Cells to Directly Identify Neovasculature in a Glioma Model. Blood. 105(1):420-5.

7. Glod, J, Kobiler D, Noel M, Maric D, and Fine HA, (2006) Monocytes adopt a Brain Microvascular Endothelial Phenotype and Participate in Vascular Repair after Brain Injury. Blood, 107(3):940-6.

8. Menon LG, Picinich S, Koneru S, Gao H, Lin SY, Koneru M, Mayer-Kuckuk P, Glod J, and Banerjee D. (2007) Differential Gene Expression Associated with Migration of Mesenchymal Stem Cells to Conditioned Medium From Tumor Cells or Bone Marrow Cells. Stem Cells. 25: 520-528.

9. Cole PD, Drachtman RA, Masterson M, Smith AK, Glod J, Zebala JA, Lisi S, Drapala DA, and Kamen BA. (2007) Phase 2B Trial of Aminopterin in Multiagent Therapy for Children with newly Diagnosed Acute Lymphoblastic Leukemia. Cancer Chemotherapy and Pharmacology, Sept 2, Epub ahead of print.

10. Jan B. Wollack, Benedette Makori, Stuti Ahlawat, Rajeth Koneru, Sonia Picinich, Angela Smith, I. David Goldman, Andong Qiu, Peter D. Cole, John Glod, and Barton Kamen. (2008) Characterization of folate uptake by choroid plexus epithelial cells in a rat primary culture model. J. Neurochem. 104(6): 1494-503.

11. Mishra PJ, Mishra PJ, Humeniuk R, Medina, D, Alexe G, Mesirov JP, Ganesan S, Glod J, and Banerjee D. (2008) Carcinoma-associated fibroblast-like differentiation of human mesenchymal stem cells. Cancer Research 68(11):4331-39.

12. Siang-Yo Lin , Jun Yang, Allen D. Everett, Charles V. Clevenger, Mythili Koneru, Barton Kamen, Debabrata Banerjee, and John Glod (In Press). The isolation of novel mesenchymal stromal cell chemotactic factors from the conditioned medium of tumor cells. Experimental Cell Research.

13. Mishra PJ, Mishra PJ, Glod JW, Banerjee D. Mesenchymal stem cells: flip side of the coin. Cancer Research. 2009 Feb 15; 69(4): 1255-8. Epub 2009 Feb 10. 14. Anton K, Glod J. Targeting the tumor stroma in cancer therapy. Current Pharmacology Biotechnology. 2009 Feb; 10(2):185-91. 15. Hui Gao, Waldemar Priebe, John Glod, Debabrata Banerjee. Activation of Signal Transducers and Activators of Transcription 3

and Focal Adhesion Kinase by Stromal Cell-Derived Factor 1 Is Required for Migration of Human Mesenchymal Stem Cells in Response to Tumor Cell-Conditioned Medium. Stem Cells Apr 2009; 27: 857 - 865; doi:10.1002/stem.23

Recent Abstracts Mishra P., Mishra P., Humeniuk R., Glod J., and Banerjee D., Mesenchymal stem cells express markers of myofibroblast lineage after long-term exposure to conditioned medium from tumor cells. Submitted for presentation at American Association for Cancer Research Meeting, April 14-18, 2007. Los Angeles CA. Lin JY, Kamen BA, Banerjee D, and Glod J., Hepatoma-derived growth factor is a tumor-derived mesenchymal stem cell chemoattractant. Submitted for presentation at American Association for Cancer Research Meeting, April 14-18, 2007. Los Angeles CA. Lin JY, Kamen BA, Banerjee D, and Glod J., Cyclophilin B is a tumor-derived mesenchymal stem cell chemoattractant. Submitted for presentation at Keystone Symposia, Stem Cells and Cancer, March 2-7, 2007. Keystone CO. C. Research Support

Ongoing Research Support 1. Children’s Brain Tumor Foundation

The role of Monocytes in Brain Tumor Angiogenesis PI J. Glod 5% effort 1/1/07 – 11/30/2009 $150,000

2. New Jersey Commission on Brain Injury Research The Role of Bone Marrow Cells in Repair of the Blood Brain Barrier After Injury PI J. Glod 10% effort 7/1/2008 – 6/30/2010 $300,000


PHS 398/2590 (Rev. 11/07) Page

Completed Support 1. New Jersey Science and Technology Commission Umbilical cord blood derived mesenchymal stem cells for tumor targeting P.I. D. Banerjee Percent effort of J Glod 10% 1/16/06 – 1/15/07 $250,000 2. The Beez Foundation; Gene Modified Mesenchymal Stromal Cells for Therapy of Brain Tumors; P.I. J. Glod Percent effort of J. Glod 10%; 2/01/05-1/31/06; direct costs $20,000 3. 05-2002-CCR-E0, The New Jersey State Commission on Cancer Research The Role of Endothelial-like Monocytic Cells in Angiogenesis in CNS Tumors P.I. J. Glod 50% effort 6/01/04-5/31/06 $45,000 4. Foundation of UMDNJ Grants Program Mechanisms regulating the recruitment of bone-marrow stromal cells for tumor stroma P.I. J. Glod, 10% 06/01/05-05/30/06 $25,000 5. 05-2406-CCR-EO NJ Commission on Cancer Research Bone marrow derived MSCs for therapy of liver Mets of CRC P.I. D.Banerjee, Percent effort of J. Glod 20% 06/01/05-05/30/06 $42,750



NAME Barth D. Grant eRA COMMONS USER NAME BarthGrant


EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such


(if applicable)


University of Virginia, Charlottesville VA B.A. 1985-1989 Biology/Chemistry Princeton University, Princeton NJ M.A., Ph.D. 1989-1996 Molecular Genetics Columbia University College of Physicians and Surgeons, New York NY postdoc 1996-2001 Cell Biology

Personal Statement: My laboratory pioneered the use of C. elegans as a system to dissect the molecular mechanisms underlying membrane traffic. Most of this work has focused on endocytosis and endocytic recycling mechanisms. In many cases we have also extended our work into mammalian cell systems showing that the new regulators of endocytic traffic that we identified in C. elegans have orthologs that perform similar functions in mammalian cells. B) Positions and Honors: 1996-2001 Postdoctoral Fellow. Columbia University College of Physicians and Surgeons, Department of Biochemistry and Molecular Biophysics. David I. Hirsh, Advisor. 2001-2007. Assistant Professor, Graduate Faculty, Rutgers University, Department of Molecular Biology and Biochemistry, Piscataway NJ. 2007-present. Associate Professor with Tenure, Graduate Faculty, Rutgers University, Department of Molecular Biology and Biochemistry, Piscataway NJ. Awards: National Institutes of Health Postdoctoral Fellowship 1996-1999. March of Dimes Basil O’ Connor Starter Scholar Research Award 2003-2004. Searle Scholar Award 2003-2006 Grant Review Panels: 2002, 2008 Division of Cellular Organization, National Science Foundation (Ad hoc) 2005-2006, 2008, 2010 National Institutes of Health, SYN Study Section [Synapses, Cytoskeleton, and Trafficking] (Ad hoc) C) 15 Selected Publications (Out of a total of 44): Tsvika Greener* Barth Grant* Yinhua Zhang, Xufeng Wu, Lois E. Greene, David Hirsh, and Evan

Eisenberg (2001) Caenorhabditis elegans auxilin: a J-domain protein essential for clathrin-mediated endocytosis in vivo. Nature Cell Biology. 3(2): 215-219 PMID: 11175756 *These authors contributed equally to this work.

Sharron X. Lin*, Barth Grant*, David Hirsh and Frederick R. Maxfield (2001) Rme-1 Regulates the Distribution and Function of the Endocytic Recycling Compartment in Mammalian Cells. Nature Cell Biology. 3(6): 567-572. PMID: 11389441 *These authors contributed equally to this work.

Barth Grant, Yinhua Zhang, Marie-Christine Paupard, Sharron X. Lin, David H. Hall and David Hirsh (2001) Evidence that RME-1, a conserved C. elegans EH domain protein, functions in endocytic recycling. Nature Cell Biology. 3(6): 573-579. PMID: 11389442

John A. Picciano, Nadia Ameen, Barth D. Grant and Neil A. Bradbury (2003) Rme-1 Regulates The Recycling of the Cystic Fibrosis Transmembrane Conductance Regulator. American Journal of Physiology: Cell Physiology. 285(5):C1009-18 .

Miyuki Sato, Ken Sato, Paul Fonarev, Chih-Jen Huang, Willisa Liou and Barth D. Grant (2005) Caenorhabditis elegans RME-6 is a novel regulator of RAB-5 at the clathrin-coated pit. Nature Cell Biology 7(6):559-69. PMID: 15895077 See also News and Views discussion of this paper Nature Cell Biology (2005) 7(6):548-50.

Carlos Chih-Hsiung Chen, Peter J. Schweinsberg, Darren P. Mareiniss, Eric Lambie, and Barth D. Grant (2006) RAB-10 Is Required for Endocytic Recycling in the C. elegans Intestine. Molecular Biology of the Cell. 17(3):1286-97. PMID: 16394106

Clifford M. Babbey, Nahid Ahktar, Exing Wang, Carlos Chih-Hsiung Chen, Barth D. Grant and Kenneth Dunn (2006) Rab10 regulates membrane transport through early endosomes of polarized Madin-Darby canine kidney cells. Molecular Biology of the Cell. 17(7):3156-75. PMID: 16641372

Zita Balklava, Saumya Pant, Hanna Fares, and Barth Grant (2007) Genome-wide analysis identifies a general requirement for polarity proteins in endocytic traffic. Nature Cell Biology 9(9):1066-73. PMID: 17704769. See also News and Views discussion of this paper Nature Cell Biology (2007) 9(9):1027-9..

Anbing Shi, Saumya Pant, Zita Balklava, Carlos Chih-Hsiung Chen, Vanesa Figueroa, and Barth D. Grant. (2007) A novel requirement for C. elegans Alix/ALX-1 in RME-1 mediated membrane transport. Current Biology, 17(22):1913-24. PMID: 17997305

Miyuki Sato, Ken Sato, Willisa Liou, Saumya Pant, Akihiro Harada and Barth D Grant. (2008) Regulation of endocytic recycling by C. elegans Rab35 and its regulator RME-4, a coated-pit protein. EMBO Journal, 27(8):1183-96. PMID: 18354496 PMCID: PMC2367398

Ken Sato, Glen G. Ernstrom, Shigeki Watanabe, Robby M. Weimer, Chih-Hsiung Chen, Miyuki Sato, Ayesha Siddiqui, Erik M. Jorgensen, Barth D. Grant. (2008) Differential requirements for clathrin in receptor-mediated endocytosis and maintenance of synaptic vesicle pools. Proc Natl Acad Sci USA, 106(4):1139-44. PMID: 19151157 PMCID: PMC2633560

Barth D. Grant and Julie G. Donaldson (2009) Pathways and Mechanisms of Endocytic Recycling. Nature Reviews Molecular Cell Biology, 10(9):597-608. PMID: 19696797

Vincent Popoff, Gonzalo A. Mardones, Valérie Chambon, Danièle Tenza, Patricia V. Burgos, Anbing Shi, Philippe Benaroch, Sylvie Urbé, Christophe Lamaze, Barth D. Grant, Graça Raposo, and Ludger Johannes. (2009) Analysis of Articulation Between Clathrin and Retromer in Retrograde Sorting on Early Endosomes. Traffic, Dec;10(12):1868-80. PMID: 19874558

Anbing Shi, Lin Sun, Riju Banerjee, Michael Tobin, Yinhua Zhang, Barth D. Grant. (2009) Regulation of endosomal clathrin and retromer mediated endosome to Golgi retrograde transport by the J-domain protein RME-8. EMBO Journal, Nov 4;28(21):3290-302. PMID: 19763082 PMCID: PMC2776105

Saumya Pant, Mahak Sharma, Kruti Patel, Steve Caplan, Chavela Carr, Barth D. Grant. (2009) AMPH-1/Amphiphysin/Bin1 functions with RME-1/Ehd in endocytic recycling. Nature Cell Biology, Dec;11(12):1399-410. PMID: 19915558, PMCID: PMC2788952

GRANT SUPPORT (Principal Investigator: Barth Grant)

Research Funding – last 3 years 2003-2012 National Institutes of Health GM67237 “Endocytosis and Recycling in C. elegans

and Mammals.” $1,745,000 direct costs 2009-2011 National Institutes of Health 3R01GM067237-07S1 Administrative Supplement to

“Endocytosis and Recycling in C. elegans and Mammals.” $203,494 direct costs 2009-2011 National Institutes of Health R21 DK082854-01 “Regulation of Apical Specific

Endocytosis in the C. elegans Intestine” Barth Grant PI $275,000 direct costs

2009-2011 National Institutes of Health R21 AI077805-01A1 “C. elegans as a model for ricin intoxication” Barth Grant Co-PI $120,000 direct costs

NAME

Samuel I. Gunderson, Ph.D. eRA COMMONS USER NAME

SAMGUNDERSON




University of Minnesota, Minneapolis B.S. 1981-1984 Genetics & Cell Biology University of Wisconsin, Madison Ph.D. 1984-1990 Genetics European Molecular Biol. Lab, Heidelberg 1990-1996 Biochemistry & RNA processing A. Professional Experience 1990 to 1996 Postdoctoral Fellow at the EMBL Heidelberg, Germany 1997 to 2004 Assistant Professor, Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 2004 to present Associate Professor, Dept. Mol. Biol. & Biochem. Rutgers Univ., Piscataway, NJ Honors and Awards 1990 - 1992 Von Humboldt Postdoctoral Fellowship 1992 - 1993 EMBO Postdoctoral Fellowship 1994 - 1996 Deutsche Forshungsgemeinshaft Postdoctoral Fellowship Grant Review Panels NIH NRSA Nov 2006 - present (8 times) A postdoctoral and pre-doctoral Fellowship review panel. NIH CDF1 June 2005 and Oct. 2006 (Ad hoc) Review of RO1 grants. NSF Ad Hoc reviewer B. Selected Peer-reviewed publications Beckley S.A., Liu P., Stover M.L., Gunderson S.I., Lichtler A.C., Rowe D.W. (2001) Reduction of target gene expression by a modified U1 snRNA. Mol Cell Biol. 21:2815-25. Phillips, C., Jung, S., and Gunderson, S.I. (2001) Regulation of nuclear poly(A) addition controls the expression of Immunoglobulin M secretory-mRNA. EMBO J. 20: 6443-6452. Ko, B., and Gunderson, S.I. (2002) Identification of new poly(A) polymerase-inhibitory proteins capable of regulating pre-mRNA polyadenylation. J. Mol. Biol. 318: 1189-1206. Guan, F., Palacios, D., Hussein, R.I., and Gunderson, S.I. (2003) Determinants within an 18 amino acid U1A autoregulatory domain that uncouple cooperative RNA binding, inhibition of polyadenylation and homodimerization. Molecular and Cellular Biology 23: 3163-3172. Fortes,P., Cuevas, Y., Guan,F., Liu, P., Pentlicky, S., Jung, S., Martínez-Chantar , M.L., Prieto, J., Rowe, D., and Gunderson, S.I. (2003) Inhibiting expression of specific genes in mammalian cells using modified U1 snRNPs targeted to terminal exons of pre-mRNA. Proc. Natl. Acad. Sci. USA 100: 8264-8269. Phillips, C. and Gunderson S.I. (2003) Sequences adjacent to the 5’ splice site control U1A binding upstream of the IgM heavy chain secretory poly(A) site. J. Biol. Chem. 278: 22102-22111.

Akum, B.F., *Chen, M., *Gunderson, S.I., Riefler, G.M., Scerri-Hansen, M.M., and Firestein, B.L. (2004). Cypin regulates dendrite patterning in hippocampal neurons by promoting microtubule assembly. Nature Neuroscience 7:145-152. * Note: acknowledged that second and third authors made equal contributions. Phillips, C. Pachikara, N, and Gunderson S.I. (2004) U1A inhibits cleavage at the IgM heavy chain secretory poly(A) site by binding between the two downstream GU-rich regions. Molecular and Cellular Biology 24:6162-6171. Miranda TB, Khusial P, Cook JR, Lee JH, Gunderson SI, Pestka S, Zieve GW, Clarke S. (2004). Spliceosome Sm proteins D1, D3, and B/B’ are asymmetrically dimethylated at arginine residues in the nucleus". BBRC 323:382-387. Lee JH, Cook JR, Yang ZH, Mirochnitchenko O, Gunderson S, Felix AM, Herth N, Hoffmann R, Pestka S. (2005) PRMT7: A new protein arginine methyltransferase that synthesizes symmetric dimethylarginine. J. Biol. Chem. 280:3656-64 Ma, J., Gunderson, S.I., and Phillips, C. (2006) "Non snRNP U1A levels decrease during mammalian B cell differentiation and release the IgM secretory poly(A) site from repression." RNA Journal 12:122-132. Guan*, F., Caratozzolo*, R.M., Goraczniak, R., Ho, E.S., and Gunderson, S.I. (2007). A bipartite U1 site represses U1A expression by synergizing with PIE to inhibit nuclear polyadenylation. RNA. 13:2129-40. Goraczniak, R., and Gunderson, S.I. (2008) The HPV16 3'UTR regulatory element inhibits expression by binding CUG binding protein 1. J Biol Chem. 283:2286-96. (Epub 2007 Nov 27). Abad X, Vera M, Jung SP, Oswald E, Romero I, Amin V, Fortes P, Gunderson SI. (2008) Requirements for gene silencing mediated by U1 snRNA binding to a target sequence. Nucleic Acids Res. 36:2338-52. Jankowska A, Gunderson SI, Andrusiewicz M, Burczynska B, Szczerba A, Jarmolowski A, Nowak-Markwitz E, Warchol JB. (2008) Reduction of human chorionic gonadotropin beta subunit expression by modified U1 snRNA caused apoptosis in cervical cancer cells. Mol Cancer. 7:26 Li, Y; Ho, Eric; Gunderson, SI; Kiledjian, Mike (2009) Mutational analysis of a Dcp2 binding element reveals general enhancement of decapping by 5' end stem-loop structures. Nucleic Acids Res. 37:2227-37. Collaboration between two labs. Eric Ho is a Gunderson lab graduate student. Goraczniak, R., Behlke, M and Gunderson, S.I. (2009) U1 Adaptors: a novel gene silencing technology. Nat Biotechnol. 27:257-63. Work was featured on the cover page and also highlighted in Nature journal. In Press Wypijewski K, Hornyik C, Shaw JA, Stephens J, Goraczniak R, Gunderson SI, Lacomme C. (2009) Ectopic 5' splice sites inhibit gene expression by engaging RNA surveillance and silencing pathways in plants. Plant Physiol. In press Aug 2009. Dr. Goraczniak is from the Gunderson lab. Ho ES, Jakubowski CD, Gunderson SI. (2009) iTriplet, a rule-based nucleic acid sequence motif finder. Algorithms Mol Biol. 2009 Oct 29;4(1):14. [Epub ahead of print]. All authors are from Gunderson lab. Reid DC, Chang BL, Gunderson SI, Alpert L, Thompson WA, Fairbrother WG. (2009) Next-generation SELEX identifies sequence and structural determinants of splicing factor binding in human pre-mRNA sequence. RNA. 2009 Oct 27.

http://www.ncbi.nlm.nih.gov/pubmed/19874606?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=1




PHS 398/2590 (Rev. 05/01) Page _______ Biographical Sketch Format Page

BIOGRAPHICAL SKETCH

NAME Max M. Häggblom



INSTITUTION AND LOCATION DEGREE (if applicable)


University of Helsinki, Finland B.S. 1985 Biology University of Helsinki M.S. 1986 General Microbiology University of Helsinki Ph.D. 1989 General Microbiology NYU Medical Center, New York Post-Doc 1988-1991 Environmental Medicine /

Microbiology A. Positions and Honors. Positions and Employment 1991-1993 Research Assistant Professor, Institute of Environmental Medicine, NYU Medical Center, NY. 1991-pres. Docent (Applied Microbiology), University of Helsinki, Finland. 1996-pres. Docent (Environmental Microbiology), University of Jyväskylä, Finland. 1993-1997 Assistant Research Professor, Center for Agricultural Molecular Biology, Rutgers University,

New Brunswick, NJ. 1997-1998 Associate Research Professor, Biotechnology Center for Agriculture and the Environment,

Rutgers University 1998-1999 Assistant Professor, Dept. of Biochemistry and Microbiology, Rutgers University 1999-2003 Associate Professor, Dept. of Biochemistry and Microbiology, Rutgers University 2000-2001 Visiting Professor, Dept. of Applied Chemistry and Microbiology, University of Helsinki, Finland

(sabbatical appointment). 2003-pres. Professor, Dept. of Biochemistry and Microbiology, Rutgers University 2008-pres. Chair, Dept. of Biochemistry and Microbiology, Rutgers University Other Positions and Experience 1995-2006 Editorial Board, Applied and Environmental Microbiology 1998-pres. Editorial Board, FEMS Microbiology Ecology 2003-pres. Editor, FEMS Microbiology Ecology 2004-pres. Microbiology Undergraduate Program Director, Rutgers University 2006-2007 Chair Elect, Division Q (Applied and Environmental Microbiology) American Society for Microbiology 2007-2008 Chair, Division Q (Applied and Environmental Microbiology), American Society for Microbiology. Member, American Society for Microbiology, American Chemical Society, Society for Industrial Microbiology, Theobald

Smith Society (local ASM branch), Society for Environmental Toxicology and Chemistry Canadian Natural Science and Engineering Research Council (NSERC) site-visit committee member to review NSERC's

Research Network application on northern environmental technologies, 2001. Chair, 34th Mid-Atlantic Industrial & Hazardous Waste Conference, Sept. 20-21, 2002, New Brunswick. Chair, International Conference on Arctic Microbiology, March 21-25, 2004, Rovaniemi, Finland. Canadian Natural Science and Engineering Research Council (NSERC) site-visit committee member to review NSERC's

Research Network application on metals in the holistic environment, 2004. U.S. Department of Energy Office of Science NABIR program review panel member, 5/2004. Review panel, Office of Environmental and Biological Research (OBER), U.S. Department of Energy program area of

Subsurface Microbial Ecology and Community Dynamics in the Environmental Science Research Division, 8/2006. Honors 1999 Rutgers University Board of Trustees Research Fellowship for Scholarly Excellence2003 Cook College/New Jersey Agricultural Experiment Station Sustained Research Excellence Award 2010 Waksman Award, Theobald Smith Society

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B. Selected peer-reviewed publications (from over 100). Häggblom MM (1992) Microbial breakdown of halogenated aromatic pesticides and related compounds. FEMS

Microbiol. Rev. 103:29-72. Song B, Palleroni NJ, Häggblom MM (2000) Isolation and characterization of diverse halobenzoate-degrading

denitrifying bacteria from soils and sediments. Appl. Environ. Microbiol. 66:3446-3453. Song B, Palleroni NJ, Kerkhof LJ, Häggblom MM (2001) Characterization of halobenzoate-degrading denitrifying

Azoarcus and Thauera isolates, and description of Thauera chlorobenzoica sp. nov. Int. J. Syst. Evolut. Microbiol. 51:589-602.

Vargas C, Fennell DE, Häggblom MM (2001) Anaerobic reductive dechlorination of chlorinated dioxins in estuarine sediments. Appl. Microbiol. Biotechnol 57:786-790.

Daane LL, Harjono I, Zylstra GJ, Häggblom MM (2001) Isolation and characterization of polycyclic aromatic hydrocarbon-degrading bacteria associated with the rhizosphere of salt marsh plants. Appl. Environ. Microbiol. 67:2683-2691.

Voordeckers J, Fennell DE, Jones K, Häggblom MM (2002) Anaerobic biotransformation of tetrabromobisphenol A, tetrachlorobisphenol A, and bisphenol A in estuarine sediments. Environ. Sci. Technol. 36:696-701.

Turpeinen R, Kairesalo T, Häggblom MM (2004) Microbial activity and community structure in arsenic, chromium and copper contaminated soils. FEMS Microbiol. Ecol. 47:39-50.

Fennell DE, Nijenhuis I, Wilson SF, Zinder SH, Häggblom MM (2004) Dehalococcoides ethenogenes strain 195 reductively dechlorinates diverse chlorinated aromatic pollutants. Environ. Sci. Technol. 38:2075-2081.

Fennell DE, Rhee S-K, Ahn Y-B, Häggblom MM, Kerkhof LJ (2004) Detecting the dehalogenating microorganism in a sulfidogenic, 2-bromophenol-utilizing enrichment by T-RFLP fingerprinting of ribosomes. Appl. Environ. Microbiol. 70:1169-1175.

Ravit B, Häggblom MM, Ehrenfeld JG (2005) Salt marsh rhizosphere affects microbial biotransformation of the widespread halogenated contaminant tetrabromobisphenol A (TBBPA). Soil Biol. Biochem. 37:1049-1057.

Ahn Y-B, Häggblom MM, Fennell DE (2005) Co-amendment with halogenated compounds enhances anaerobic microbial dechlorination of 1,2,3,4-tetrachlorodibenzo-p-dioxin and 1,2,3,4-tetrachlorodibenzofuran in estuarine sediments. Environ. Toxicol. Chem. 24:2775-2784.

Somsamak P, Richnow HH, Häggblom MM (2006) Carbon isotope fractionation during anaerobic degradation of methyl tert-butyl ether (MTBE) under sulfate-reducing and methanogenic conditions. Appl. Environ. Microbiol. 72:1157-1163.

Narasingarao P, Häggblom MM (2006) Sedimenticola selenatireducens, gen. nov., sp. nov., an anaerobic selenate-respiring bacterium isolated from estuarine sediment. Systematic and Applied Microbiology 29:382-388.

Ravit B, Ehrenfeld JG, Häggblom MM (2006) Effects of wetland vegetation on rhizosphere microbial communities: A comparison of disturbed versus undisturbed estuarine sediments. Soil Biol. Biochem. 38:2359-2371.

Männistö MK, Tiirola M, Häggblom MM (2007) Microbial communities in Arctic fjelds of Finnish Lapland are stable but highly pH dependent. FEMS Microbiology Ecology 59:452-465.

Narasingarao P, Häggblom MM (2007) Anaerobic selenate-respiring bacteria are diverse and ubiquitous in aquatic sediments. Appl. Environ. Microbiol. 73:3519-3527.

Ahn Y-B, Häggblom MM. Kerkhof LJ (2007) Comparison of anaerobic microbial communities amended with halogenated compounds to enhance dechlorination of 1,2,3,4-tetrachlorodibenzo-p-dioxin in estuarine sediments. FEMS Microbiol Ecol. 61:362-371.

Launen LA, Dutta J, Turpeinen R, Eastep ME, Dorn R, Buggs VH, Leonard JW, Häggblom MM (2008) Characterization of the indigenous PAH-degrading bacteria of the Spartina alterniflora-dominated salt marshes in the New York / New Jersey harbor. Biodegradation 19:347-363.

George KW, Häggblom MM (2008) Microbial O-methylation of the flame retardant tetrabromobisphenol-A. Environ. Sci. Technol. 42:5555–5561.

Ahn Y-B, Liu F, Fennell DE, Häggblom MM (2008) Biostimulation and bioaugmentation to enhance dechlorination of polychlorinated-p-dioxins in contaminated sediments. FEMS Microbiology Ecology 66:271-281.

Youngster LKG, Somsamak P, Häggblom MM (2008) Effects of co-substrates and inhibitors on the anaerobic O-demethylation of methyl tert-butyl ether (MTBE). Appl. Microbiol. Biotechnol. 80:1113-1120.

Ahn Y-B, Kerkhof LJ, Häggblom MM (2009) Desulfoluna spongiiphila sp. nov., a dehalogenating bacterium in the Desulfobacteraceae from the marine sponge Aplysina aerophoba. Int. J. System. Evol. Microbiol. 59:2133-2139.

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Männistö MK, Tiirola M, Häggblom MM (2009) Effect of freeze-thaw cycles on bacterial communities of Arctic tundra soil. Microbial Ecology 58:621–631.

Krumins V, Park J-W, Son E-K, Rodenburg LA, Kerkhof LJ, Häggblom MM, Fennell DE (2009) Sustained PCB dechlorination enhancement in Anacostia River sediment. Water Research 43:4549-4558.

Youngster LKG, Kerkhof LJ, Häggblom MM (2010) Community characterization of anaerobic methyl tert-butyl ether (MTBE) degrading enrichment cultures. FEMS Microbiol. Ecol. 72:279-288.

Selected Books and Book Chapters Häggblom MM, Milligan PW (2000) Anaerobic degradation of halogenated pesticides: influence of alternate electron

acceptors. In: Bollag J-M, Stotzky G (eds) Soil Biochemistry, Vol. 10., Marcel Dekker, New York, pp. 1-34. Häggblom MM, Bossert ID (Editors) (2003) Dehalogenation: Microbial Processes and Environmental Applications,

Kluwer Academic Publishers, Boston. Häggblom MM, Ahn Y-B, Fennell DE, Kerkhof LJ, Rhee SK (2003) Anaerobic dehalogenation of organohalide

contaminants in the marine environment. In: Laskin AI, Gadd GM, Bennett J (eds) Advances in Applied Microbiology 53:61-84. Elsevier Science, San Diego

Kerkhof LJ, Häggblom MM (2007) Detecting active bacteria involved in biodegradation in the environment. In: Diaz E (ed) Microbial Biodegradation: Genomics and Molecular Biology, Caister Academic Press, pp. 55-70.

C. Research Support Current Quantifying enhanced microbial dehalogenation impacting the fate and transport of organohalide mixtures in

contaminated sediments. DoD/SERDP, 03/06-2/11. PI. The overall objectives are develop techniques and amendments that enhance and accelerate microbial dehalogenation of organohalide mixtures in contaminated sediments.

Impact of climate fluctuations on microbial communities responsible for carbon and nitrogen cycling in Arctic soils. Academy of Finland, 422,400 Euro, 01/08-12/11, PI

The study examines the role of different bacterial groups in C and N cycling in Arctic soil environments and assess the selection mechanisms promoting the dominance of key species in changing temperature regimes. Field and laboratory experiments are combined to elucidate the metabolic fingerprints of the dominant bacterial species.

IPY Microbial subzero activity and its impact on biogeochemical processes in frozen tundra and permafrost. National Science Foundation, $538,647, 01/01/08-12/31/10, Co-PI

The overall objective is to reach an understanding of the subzero microbial processes and their impacts on permafrost dynamics including thermal degradation in an interdisciplinary systems study combining mechanistic mathematical modeling with modern molecular-genetic techniques, environmental physics and biogeochemistry.

D. Graduate Students and Post-Doctoral Associates Graduate Students: Peter Milligan (1994-1998; M.S. 1995, Ph.D. 1998), Sonia Vela (1994-1997, M.S. 1997;co-advisor), Bongkeun Song (1996-2000; Ph.D. 2000), Riina Turpeinen (1998-2002; University of Helsinki, Finland, M.S. 1998, Ph.D. 2002), Jayeeta Dutta (1999-2000; M.S. 2000), Piyapawn Somsamak (2000-2005, Ph.D. 2005), Beth Ravit (2001-2005, Ph.D. 2005, co-advisor), E. Jane Pavlik (1999-2005, Ph.D. 2006), Michael Fleming (2000-2006, M.S. 2006, co-advisor), Priya Narasingarao (2001-2006, Ph.D. 2006), Leslie Wickam (2003-2005, M.S. 2005), Laura Youngster (2004-2009), Jessica McCormick (2006-2010, co advisor), Hui Liu (2005-), Isabel Horna Gray (2006-), Ines Rauschenbach (2007-), Nora Lopez (2007-, co-advisor), Sanna Kuokka (2009-, University of Helsinki, co-advisor). Post-doctoral and Research Associates: Esteban Monserrate (1994-1996), Cecilia Vargas (1996-1998), Victoria Knight (1996-1999), Lori Daane (1997-1999), Miao Y. Wang (1997-1998), Loren Launen (1999-2001), Matthew Caldwell (2000-2001), Donna Fennell (1999-2001), Sung-Keun Rhee (2000-2002), Peter Kourtev (2001-2002), Young-Beom Ahn (2001-2008), Minna Männistö (2001-2004), Sari Stark (2001-2004), Katri Mattila (2001-2005), Jong-Wook Park (2006-pres.), Duong Minh Vien (2008-2009).

BIOGRAPHICAL SKETCH Provide the following information for the key personnel in the order listed for Form Page 2.


NAME Beatrice Haimovich eRA COMMONS USER NAME HAIMOVICH





Tel-Aviv University, Israel B.Sc. 1980 Life Sciences University of Pennsylvania, Philadelphia Ph.D. 1986 Biochemistry

A. Positions and Honors. Positions and Employment: 1986-1988 Post-Doctoral fellow, Department of Biochemistry, University of Pennsylvania, Philadelphia. 1988-1992 Post-Doctoral fellow, Department of Microbiology and Howard Hughes Institute, University of

Pennsylvania, Philadelphia. 1992-2000 Assistant Professor, Department of Surgery, UMDNJ-RWJ Medical School, New Brunswick, NJ. 1993-To date Member of the Joint Program in Molecular Biosciences 1998-To data Joint appointment, Department of Biochemistry, UMDNJ-RWJ Medical School 2000-To date Associate Professor, Department of Surgery, UMDNJ-RWJ Medical School, New Brunswick, NJ 2001-To date Member, Cancer Institute of NJ B. Selected peer-reviewed publications (in chronological order). (Publications selected from 34 peer-reviewed publications).

2. Haimovich, B., E. Bonilla, J. Casadei, and R. Barchi. 1984. Immunochemical localization of the mammalian voltage-dependent

sodium channel using polyclonal antibodies against the purified proteins. J. Neurosci. 4:2259-2268. 3. Haimovich, B., J.C. Tanaka, and R.L. Barchi. 1986. Developmental appearance of sodium channel sub-types in rat skeletal muscle

cultures. J. Neurochem. 47:1148-1153. 4. Haimovich, B., D.L. Schotland, W.F. Fieles and R.L. Barchi. 1987. Sodium channel subtypes identified in rat skeletal muscle using

channel specific monoclonal antibodies. J. Neurosci. 7:2956-2966. 5. Hayashi, Y., B. Haimovich, A. Reszka, D. Boettiger, and A. Horwitz. 1990. Expression and function of chicken integrin beta1 subunit

and its cytoplasmic domain mutants in mouse NIH 3T3 cells. J.Cell.Biol.110:175-184. 6. Haimovich, B. , B.J. Aneskievich, and D. Boettiger. 1991. Cellular partitioning of beta-1 integrins and their phosphorylated forms is

altered after transformation by Rous sarcoma virus or treatment with cytochalasin D. Cell Regulation 2:271-283. 7. Aneskievich, B.J., B. Haimovich, and D. Boettiger. 1991. Phosphorylation of integrin in differentiating ts-Rous sarcoma virus-infected

myogenic cells. Oncogene 6:1381-1390. 8. Lipfert, L., B. Haimovich, M.D. Schaller, B.S. Cobbe., J.T. Parsons, and J.S. Brugge. 1992. Integrin-dependent phosphorylation and

activation of the protein tyrosine kinase pp125FAK in platelets. J. Cell Biol. 119:905-912. 9. Haimovich, B., L. Lipfert, J.S. Brugge, and S.J. Shattil. 1993. Platelet tyrosine phosphorylation and cytoskeletal reorganization are

triggered by the interaction of integrin adhesion receptors with fibrinogen and collagen matrices. J. Biol. Chem. 268:15868-15877. 10. Shattil, S.J., Haimovich, B., M. Cunningham, L. Lipfert,T. Parsons, M. Ginsberg, and J.S. Brugge1994. Tyrosine phosphorylation of

pp125FAK in platelets requires coordinated signaling through integrin and agonist receptors. J. Biol. Chem. 269:14738-14745. 12. Katz, D.A., Haimovich, B., and R.S. Greco. 1994. Neutrophil activation by expanded polytetrafluoroethylene is dependent on the

induction of protein phosphorylation. Surgery. 116:446-455.

13. Katz, D.A., Haimovich, B., and R.S. Greco. 1995. The FcγRII, FcγRIII, and CD18 receptors mediate in part neutrophil activation on a

plasma coated ePTFE surface. Surgery. 118:154-161. 14. Haimovich, B. and J.C. Tanaka. 1995. Magainin-induced cytotoxicity in eukaryotic cells: Kinetics, dose-response, and channel

characteristics. Biochimica et Biophysica Acta. 149-158. 15. Haimovich, B., N. Kaneshiki, and P. Ji. 1996. Protein Kinase C regulates tyrosine phosphorylation of pp125FAK in platelets adherent

to fibrinogen. Blood. 87:152-161. 17. Haimovich, B. Regan, C., DiFazio L., Ginalis, E.M., P, Ji., Purohit, U., Bowley, R.B., Bolen, J., and R.S. Greco. 1996 The FcγRII

receptor triggers pp125FAK phosphorylation in platelets. J. Biol. Chem. 271:16332-16337. 18. Haimovich, B. DiFazio L., Katz, D., Greco, R.S., Dror, Y., and A. Freeman. 1997 A new method for membrane construction on

ePTFE vascular grafts: effect on surface morphology and platelet adhesion. Journal of Applied Polymer Science. 63:1391-1400. 19. De La Cruz, C. Haimovich, B. and R.S. Greco. 1998. Immobilized IgG and Fibrinogen differentially effect the cytoskeletal

organization and bactericidal function of adherent neutrophils. Journal of Surgical Research 80:28-34. 21. Moussazadeh, M. Ji, P. and B. Haimovich. 1998. PKC-δ activation and tyrosine phosphorylation in platelets. FEBS Lett. 438:225-

230. 22. Haimovich, B., Ji, P. Ginalis, E. Kramer, R. and Greco, R.S. 1999. Phospholipase A2 enzymes regulate αIIbβ3-mediated, but not

FcγRII receptor-mediated, pp125FAK phosphorylation in platelets. Thrombosis and Haemostasis 81:618-624. 23. Ji, P. and Haimovich, B. 1999. Integrin αIIbβ3-mediated pp125FAK phosphorylation and platelet spreading on fibrinogen are

regulated by PI3-kinase Biochimica et Biophysica Acta. 1448:543-552. 24. Izaguirre, G. Aguirre, L. Ji, P. Aneskievich, B. and Haimovich, B. 1999. Tyrosine phosphorylation of alpha-actinin in activated

Platelets, J. Biol. Chem., 274:37012-37020. 25. Nazdam J, De La Cruz, C. Greco, R.S. and B. Haimovich. 2000. Neutrophil adhesion to vascular prosthetic surfaces triggers a non-

apoptotic cell death Annals of Surgery, 231:587-599. 27. Izaguirre, G. Aguirre, L. Hu, Y-A. Young H.Y., Schlaepfer, D.D., Aneskievich, B. and Haimovich, B. 2001. The

cytoskeletal/non-muscle isoform of α-actinin is phosphorylated on its actin-binding domain by the focal adhesion kinase. J. Biol. Chem., 276:28676-28685.

28. Chang, S. Popowich, Y, Greco R.S. and Haimovich, B. 2003. Neutrophil survival on biomaterials is determined by surface topography. Journal of Vascular Surgery,37:1082-90.

29. von Wichert G, Haimovich B, Feng GS, Sheetz M. 2003. Force-dependent integrin-cytoskeleton linkage formation requires downregulation of focal complex dynamics by Shp2. EMBO J. 22(19):5023-35.

30. Lin SY, Raval S, Zhang Z, Deverill M, Siminovitch KA, Branch DR, Haimovich B. 2004 The protein tyrosine phosphatase SHP-1 regulates the phosphorylation of a-actinin. J Biol Chem 279:25755-25764 31. Zhang, Z., Izaguirre, G., Lin, S-Y., Lee HY., Schaefer, E., and Haimovich, B. 2004 The phosphorylation of vinculin on tyrosine residues 100 and 1065, mediated by Src kinases, affects cell spreading. Mol Biol Cell

15(9):4234-47. 32. Koterski JF, Nahvi M, Venkatesan MM, Haimovich B. 2005. Virulent Shigella flexneri causes damage to mitochondria and triggers

necrosis in infected human monocyte-derived macrophages. Infect Immun. 73(1):504-13. 33. Haimovich, B, and Venkatesan M. Shigella and Salmonella: death as a means of survival. Microbes and Infection. 2006. 8(2):568-77. 34. Zhang, Z., Lin , S-Y., Neel, BG., and Haimovich B. 2006. Phosphorylated alpha-actinin and PTP 1B coregulate the disassembly of

the FAK/Src complex and promote cell migration. J Biol Chem. 281(3):1746-54. 35. Moese S, Selbach M, Brinkmann V, Karlas A, Haimovich B, Backert S, Meyer TF. 2007. The Helicobacter pylori CagA protein

disrupts matrix adhesion of gastric epithelial cells by dephosphorylation of vinculin. Cell Microbiol.9(5):1148-61. 36. Craig DH, Haimovich B, Basson MD. 2007. Alpha-actinin-1 phosphorylation modulates pressure-induced colon cancer cell adhesion

through regulation of focal adhesion kinase-Src interaction. Am J Physiol Cell Physiol. 293(6):C1862-74. 37. Zhang, Z. Ning, G., Lee, C., Venkatesan, M., and Haimovich, B. Virulent Shigella infection enhances endogenous autophagy in

human monocytes and macrophages without altering host-cell cytotoxicity and bacterial survival. Submitted . 38. Haimovich, B. Calvano, J. Haimovich, AD, Calvano SE, Coyle, SM., and Lowry, SF. 2010. In vivo endotoxin synchronizes and

suppresses clock gene expression in human peripheral blood leukocytes. Critical Care Medicine. 38(3):751-8.

http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17217431

http://www.ncbi.nlm.nih.gov/pubmed/17898132?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

Research Support in past three years

PI: Beatrice Haimovich 01/01/2007-12/31/2009 (one year no cost extension) Source NIH-GM079255-01 Grant type R21 (total direct $250,000) Title of project Induction of Autophagy in Human Macrophages by Lipopolysaccharide Research Goals The major goals of this project are to determine whether and how LPS induces autophagy in human

macrophages PI: Beatrice Haimovich 01/01/2007-03/01/2010 Source UMDNJ Grant type Pilot grant (total $25,000) Title of project Circadian gene expression and tissue bioenergetics are altered during the acute phase of systemic

inflammation

Principal Investigator/Program Director (Last, First, Middle): HAMPSEY, Michael

HS 398/2590 (Rev. 09/04) Page Biographical Sketch Format Page 1



NAME Michael Hampsey eRA COMMONS USER NAME hampsey

POSITION TITLE Professor and Interim Chair



SUNY – Geneseo, NY B.A. 1976 Chemistry Purdue University, W. Lafayette, IN Ph.D. 1982 Biochemistry University of Rochester Medical Center, Rochester, NY Post-doc 1986 Genetics

A. Positions, Service and Honors Positions 1986 – 1992 Assistant Professor, Department of Biochemistry and Molecular Biology, Louisiana State

University Health Sciences Center, Shreveport, LA. 1992 – 1996 Associate Professor, LSUHSC, Shreveport, LA. 1996 – 2002 Associate Professor, Department of Biochemistry, UMDNJ – Robert Wood Johnson

Medical School, Piscataway, NJ. 1999 – present Member, Cancer Institute of New Jersey 2002 – present Professor, Department of Biochemistry, UMDNJ – RWJMS, Piscataway, NJ. 2007 – present Interim Chair, Department of Biochemistry, UMDNJ – RWJMS, Piscataway, NJ. Professional Service and Memberships 1993 – 1997 Member, ACS Scientific Advisory Committee: Genetic Mechanisms in Cancer. 1996 National Science Foundation – EPSCoR Site Visit: University of Southern Mississippi. 1996, 2000 Member (ad hoc), NIH Microbial Genetics and Physiology Study Section (MCB-2). 2000 National Science Foundation – Committee of Visitors: Div. Molec. & Cell. Biosciences 1999, 2000 Member (ad hoc), NIH Genome Study Section (GNM). 2000 – 2004 Member, NIH Microbial Genetics and Physiology Study Section (MBC-2). 2002 – 2004 Chairperson, NIH Microbial Genetics and Physiology Study Section (MBC-2). 1999 – present Associate Editor, Genetics. 2005 – present Member, Editorial Board, Molecular & Cellular Biology. Awards 2008 Elected Fellow – American Association for the Advancement of Science (AAAS). 2005 Selected Member – UMDNJ Master Educators’ Guild. B. Publications (selected from 67 peer-reviewed manuscripts; cited in PubMed as either Hampsey, DM or

Hampsey, M) Primary Research Articles HAMPSEY, M. and D. REINBERG (2003) Tails of intrigue: phosphorylation of RNA polymerase II mediates

histone methylation. Cell 113:429-432. CHEN, B.-S. and M. HAMPSEY (2004) Functional Interaction Between TFIIB and the Rpb2 Subunit of RNA

Polymerase II: Implications for the Mechanism of Transcription Start Site Selection. Mol. Cell. Biol. 24: 3983-3991.

KRISHNAMURTHY, S., X. HE, M. REYES-REYES, C. MOORE AND M. HAMPSEY (2004) Ssu72 is a RNA polymerase II CTD phosphatase. Mol. Cell 14:387-394.

Principal Investigator/Program Director (Last, First, Middle): HAMPSEY, Michael


CHEN, B.-S., S. MANDAL and M. HAMPSEY (2004) High-resolution protein-DNA contacts for the yeast RNA polymerase II general transcription machinery. Biochemistry 43:12741-12749.

FREIRE-PICOS, M. A., S. KRISHNAMURTHY, Z.-W. SUN AND M. HAMPSEY (2005) Evidence that the Tfg1/Tfg2 dimer interface of TFIIF lies near the active center of the RNA polymerase II initiation complex. Nucl. Acids Res. 33:5045-5052.

HAUSMANN, S., H. KOIWA, S. KRISHNAMURTHY, M. HAMPSEY and S. SHUMAN (2005) Different strategies for CTD recognition by serine5-specific CTD phosphatases. J. Biol. Chem. 280:37681-37688.

ANSARI, A. and M. HAMPSEY (2005) A role for the CPF 3’-end processing machinery in RNAP II-dependent gene looping. Genes & Dev. 19:2969-2978.

REYES-REYES, M. and M. HAMPSEY (2007) Role for the Ssu72 C-terminal domain phosphatase in RNA polymerase II transcription elongation. Mol. Cell. Biol. 27:926-936.

SINGH, B. N. and M. HAMPSEY (2007) A transcription-independent role for TFIIB in gene looping. Mol. Cell 27:806-816.

ESTRELLA, L. A., S. KRISHNAMURTHY, C. R. TIMME and M. HAMPSEY (2008) The Rsp5 E3 ligase mediates turnover of low-affinity phosphate transporters in Saccharomyces cerevisiae. J. Biol. Chem. 283:5327-5334.

GHAZY, M., X. HE, B.N. SINGH, M. HAMPSEY and C. MOORE (2009) The essential N-terminus of the Pta1 scaffold protein is required for snoRNA transcription termination and Ssu72 function but is dispensable for pre-mRNA 3’-end processing. Mol. Cell. Biol. 29:2296-2307.

KRISHNAMURTHY, S., M. A. GHAZY, C. MOORE and M. HAMPSEY (2009) Functional interaction of the Ess1 prolyl isomerase with components of the RNA polymerase II initiation and termination machineries. Mol. Cell. Biol. 29:2925-2934.

SINGH, B.N., A. ANSARI and M. HAMPSEY (2009) Detection of transient short-range chromatin interactions by 3C in yeast. Methods 48:361-367.

LAINÉ, J.-P., B.N. SINGH, S. KRISHNAMURTHY and M. HAMPSEY (2009) A physiological role for gene loops in yeast. Genes & Dev. 23:2604-2609.

Invited Review Articles (selected from 16 peer-reviewed articles) WOYCHIK, N. A. and M. HAMPSEY (2002) The RNA polymerase II machinery: structure illuminates function.

Cell 108:453-463. HAMPSEY, M. (2006) The RNA polymerase II initiation complex: looking for a place to start. Nat. Struct.

Mol. Biol. 13:564-566. M. HAMPSEY and T. G. KINZY (2007) Synchronicity: Policing multiple aspects of gene expression by Ctk1.

Genes & Dev. 21:1288-1291. HAMPSEY, M. (2007) Negative regulatory elements (ver. 2). Encyclopedia of Life Sciences, John Wiley &

Sons, Ltd, UK. http://www.mrw.interscience.wiley.com/emrw/047001590X/home. KRISHNAMURTHY, S. and M. HAMPSEY (2009) Eukaryotic transcription initiation. Curr. Biol. 19:R153-

R156. C. Research Grant Support Agency: National Institutes of Health – RO1 GM-39484 (15-18) Title: Genetic Analysis of Transcription Initiation in Yeast P.I.: M. Hampsey Period: 4/01/09 – 3/31/13 Direct Costs: $850,000 [direct costs] Agency: National Institutes of Health – GM-068887 (05-09) Title: The Coupling of mRNA Transcription and 3’-End Formation PIs: M. Hampsey and Claire Moore (Tufts Medical School) (M.H. and C.M. are co-PIs) Period: 9/01/07 – 8/31/11 Direct Costs: $1,014,901 (to M.H.) + $151,876 (Supplement for Jesús Rosado) [direct costs]

http://www.mrw.interscience.wiley.com/emrw/047001590X/home



NAME Ronald P. Hart, Ph.D. eRA COMMONS USER NAME (credential, e.g., agency login) ronhart2

POSITION TITLE Professor of Cell Biology & Neuroscience



The University of Connecticut, Storrs, CT B.S. 05/77 Biology The University of Michigan, Ann Arbor, MI Ph.D. 08/81 Molecular Biology Rockefeller University, New York, NY (Postdoc) 08/85 Molecular Biology

A. Personal Statement Our research group focuses on the role of small RNAs during early differentiation in human embryonic stem cells. We recently predicted a large set of novel microRNAs based on deep sequencing of stem cell small RNAs through bioinformatics and RNA immunoprecipitation of RISC complexes as validation. Ongoing work seeks to discover function of these novel microRNAs through innovative genome-wide strategies. We are also asking whether microRNAs regulated by histone deacetylase inhibitors mediate the induction of neurogenesis, and whether small RNAs interact with long, non-coding RNAs to place epigenetic marks on chromatin during early stem cell development. Graduate students trained in our lab helped to shape these projects and spearhead the development of technologies to answer the questions.

B. Positions and Honors

Positions and Employment 1985-1991 Assistant Professor, Rutgers University, Newark. 1991-1997 Associate Professor, Rutgers University, Newark. 1997-2002 Professor, Rutgers University, Newark. 1999- Member, W.M. Keck Center for Collaborative Neuroscience, Rutgers University, Piscataway 2002- Professor, Cell Biology & Neuroscience, Rutgers University, Piscataway.

Other Experience and Professional Memberships 2006- Member, International Society for Stem Cell Research 2009- Member, State of Connecticut Stem Cell Research Advisory Committee

C. Selected Peer-reviewed Publications (Selected from 70 peer-reviewed publications)

Most relevant to the current application 1. Goff, L.A., J.D. Davila, R. Jörnsten, S. Keles, and R.P. Hart. (2007) Bioinformatic Analysis in Neural

Stem Cell Differentiation. Journal of Biomolecular Techniques 18:205-212. PMCID: PMC2062565 2. Lakshmipathy, U., B. Love, L. A. Goff, R. Jörnsten, R. Graichen, R. P. Hart, and J. D. Chesnut (2007).

Micro RNA expression pattern of undifferentiated and differentiated human embryonic stem cells. Stem Cells & Development, 16: 1003-1016. PMCID: PMC2743486

3. Li, H., Y. Han, C. Bi, J. J. Davila, L.A. Goff, K. Thompson, M. Swerdel, C. Camarillo, C.L. Ricupero, R.P. Hart, M. Plummer, and M. Grumet. (2008) Functional differentiation of a clone resembling embryonic cortical interneuron progenitors. Dev. Neurobiol. 68: 1549-1564. PMCID: PMC2743477

4. Goff, L.A., J. Davila, M.R. Swerdel, J.C. Moore, R.I. Cohen, H. Wu, Y.E. Sun and R.P. Hart (2009) Ago2 immunoprecipitation identifies predicted microRNAs in human embryonic stem cells and neural precursors. PLoS One 4: e7192. PMCID: PMC2745660

5. Moore, J.C., S. Sadowy, M. Alikani, A.J. Toro-Ramos, M.R. Swerdel, R.P. Hart and R.I. Cohen (2009) A high-resolution molecular-based panel of assays for identification and characterization of human embryonic stem cell lines., Stem Cell Res 4: 92-106. Not NIH supported

Additional recent publications of importance to the field (in chronological order) 1. Lakshmipathy, U. and R.P. Hart (2008) Concise Review: MicroRNA Expression in Multipotent

Mesenchymal Stromal Cells, Stem Cells 26: 356-363. PMCID: PMC2673465 2. Goff, L.A, S. Boucher, C. Ricupero, S. Fenstermacher, M. Swerdel, L. Chase, C. Adams, J.D. Chesnut,

U. Lakshmipathy and R.P. Hart. (2008) Differentiating human multipotent mesenchymal cells regulate microRNAs: prediction of microRNA regulation by PDGF during osteogenesis. Experimental Hematology, 36: 1354-1369. PMCID: PMC2782644

3. Chang, Y.W., L.A. Goff, H. Li, N. Kane-Goldsmith, E. Tzatzalos, R. Hart, W. Young and M. Grumet (2009) Rapid induction of genes associated with tissue protection and neural development in contused adult spinal cord after radial glial cell transplantation., J Neurotrauma 26: 979-993. PMC Journal – In Process

4. Bail, S., M. Swerdel, L. A. Goff, R. P. Hart and M. Kiledjian. Differential Regulation of microRNA Stability. RNA, In press.

5. Lakshmipathy, U., J. Davila, R.P. Hart. Concise Review: microRNA in pluripotent stem cells. Regenerative Medicine, In press.

D. Research Support

Ongoing Research Support RC1 CA147187 Hart (PI) 03/01/10-02/28/12 “Genome-wide chromatin modification targeting by endogenous small RNAs.” We will explore the hypothesis that small RNAs direct positioning of epigenetic marks through binding of antisense ncRNA. There is no scientific or budgetary overlap. Role: PI (multiple PI project with Manolis Kellis, MIT and Broad Institute)

R21 MH085088-01A1 Hart (PI) 09/29/09-09/28/11 “Epigenetic regulation of microRNAs in neurogenesis” We will determine whether microRNAs are regulated by HDAC inhibitors in neuronal precursors via chromatin modification. This is parallel to but not overlapping with aims proposed here. Role: PI

R01 NS037060-12 Filbin (PI) 02/15/10-02/14/11 “The role of myelin in spinal cord regeneration.” Our subcontract will identify microRNAs found in neurites of DRG neurons grown in compartmentalized chambers using deep sequencing and qPCR. Role: Subcontractor

07-3067-SCR·E-0 Hart (PI) 06/15/07-06/15/10 “Overcoming myelin inhibition with microRNAs.” Agency: New Jersey Commission on Spinal Cord Research. This is a pilot project to identify neurite-specific microRNAs from cells grown on inhibitory and permissive substrates for regenerative growth. Role: PI

HESC-08-02-00 Grumet (PI); Hart (Project PI) 09/01/07-09/30/10 “Human ES Cells and Neural Transplantation.” PI: Martin Grumet. Research Project 2: “microRNA modulation of hESC differentiation into NSC.” PI: Ronald P. Hart. Agency: New Jersey Commission on Science & Technology, Stem Cell Program. We will identify novel microRNAs in human embryonic stem cells as they differentiate into neuronal precursors. Role: Co-PI

Principal Investigator/Program Director (Last, First, Middle):




NAME Sarah E. Hitchcock-DeGregori eRA COMMONS USER NAME HITCHCOCK



INSTITUTION AND LOCATION DATES ATTENDED DEGREE (if applicable) YEAR(s) FIELD OF STUDY

Smith College, Northampton, MA 9/61-6/65 A.B. 06/65 Zoology Wesleyan University, Middletown, CT 9/65-6/67 M.A. 06/67 Biology Case Western Reserve Univ., Cleveland, OH 9/67-6/70 Ph.D. 06/70 Biology

Brandeis University, Waltham, MA 9/70-8/73 Postdoc. 1970-73 Biochemistry

MRC Lab. Mol. Biology, Cambridge, UK 9/73-8/76 Res. Fellow

1973-76 Molecular Biology

A. Personal Statement The goal of the proposed research is to understand the molecular basis of tropomyosin function, a universal regulator of the actin cytoskeleton. I have recruited a team of fine collaborators and together we have the expertise, knowledge and experience to address a fundamental problem in biology: how the coiled coil protein, tropomyosin, binds to actin and its other targets and regulates the actin cytoskeleton. I am a recognized leader in my field, having studied the actin filament and its regulation during my entire career, making a number of relevant contributions. I have used biochemical and biophysical methods to address questions about the structure and function of actin and associated proteins, and was the first to apply recombinant DNA and molecular genetic strategies to understand their functions. In our recent work on tropomyosin we have verified the model for quasi-equivalent actin binding sites and defined the molecular requirements for binding. Our structural studies include the first atomic resolution structure of tropomyosin (with Norma Greenfield and Gaetano Montelione), and later an X-ray structure with Carolyn Cohen) and the structure of the overlap complex (with Greenfield and Montelione). The structures solved an unanswered question and gave fresh insights into tropomyosin and its assembly on the actin filament . Throughout this period I have remained interested in actin filament function in both muscle and non-muscle cells, and have had productive collaborations with Tom Pollard, John Condeelis, and Clare Waterman-Storer concerning actin filament dynamics and regulation of cell motility, the focus of the proposed work. Recently I have introduced a bioinformatics approach that in essence takes advantage of the experiments evolution has done in defining the critical residues of proteins for function. I took a three-week intense Molecular Evolution Workshop at the MBL in Woods Hole in the Summer, 2008, to learn the methods that we have successfully applied during the past 18 months in my lab that form the basis of the present proposal. B. Positions and Honors Positions and Employment 1973 Associate of the Physiology Course, Marine Biological Laboratory, Woods Hole, MA, Summer 1976-1985 Assistant and Associate Professor of Biological Sciences, Carnegie-Mellon University,

Pittsburgh PA 1985-present Associate Professor and Professor of Neuroscience and Cell Biology, UMDNJ-Robert Wood

Johnson Medical School Other Experience and Professional Memberships (partial list) 1976- Member, American Society for Cell Biology 1976- Member, Biophysical Society, elected Secretary, 1995-1999 1993-1999 Editorial Board, FASEB J.



1996, 1999 Gordon Research Conference on Contractile Proteins, 1996 Vice-Chair, 1999 Chair 1996-1999 Member, NIH National Arthritis and Musculoskeletal and Skin Diseases Advisory Council 2000-2006 Editorial Board, Biophysical Journal 2008- Secretary of the Faculty, Robert Wood Johnson Medical School Honors 1971-1973 Muscular Dystrophy Research Fellow 1973-1976 British-American Heart Fellow 1975-1976 NIH Special Fellow 1982-1987 NIH Research Career Development Award 2005 Distinguished Service Award, Biophysical Society C. Selected Peer-reviewed Publications (Selected from 70 peer-reviewed publications) Most relevant to the current application, and most recent 1. Singh, A. and Hitchcock-DeGregori, S.E. 2006. Dual requirement for flexibility and specificity for binding of

the coiled coil tropomyosin to its target, actin . Structure 14:43-50. 2. Greenfield, N.J., Huang, Y.J., Swapna, G.V.T., Bhattacharya, A., Rapp, B., Singh, A., Montelione, G.T., and

Hitchcock-DeGregori, S.E.. 2006. Solution NMR structure of the junction between tropomyosin molecules: Implications for actin binding and regulation. J. Mol. Biol. 364: 80-96.

3. Wawro, B., Greenfield, N.J., Wear, M.A., Cooper, J.A., Higgs, H.N. and Hitchcock-DeGregori, S.E. 2007. Tropomyosin regulates elongation by formin at the fast-growing end of the actin filament. Biochemistry 46:8146-8155.

4. Singh, A. and Hitchcock-DeGregori, S.E. 2009. A peek into tropomyosin binding and unfolding on the actin filament. PLoS One, 4 (7) e6336.

5. Hitchcock-DeGregori, S.E. and Singh, A. 2010. What makes tropomyosin an actin binding protein? A perspective. J. Struct. Biol. 170:319-324.

Additional recent publications of importance to the current application and the field (in chronological

order) 1. DesMarais, V., Ichetovkin, I., Condeelis, J., and Hitchcock-DeGregori, S.E. 2002. Spatial regulation of actin

dynamics: A tropomyosin-free, actin-rich compartment at the leading edge. J. Cell Sci. 115:4649-4660. 2. Hitchcock-DeGregori, S.E, Song, Y. and Greenfield, N.J. 2002. Functions of tropomyosin’s periodic repeats.

Biochemistry 41: 15036-15044. 3. Greenfield, N.J., Swapna, G.V.T., Huang, Y., Palm,T., Graboski, S., Montelione, G.T., and Hitchcock-

DeGregori, S.E.. 2003. The structure of the carboxyl terminus of striated -tropomyosin in solution reveals an unusual parallel arrangement of interacting -helices. Biochemistry 42:614-619.

4. Palm, T., Greenfield, N.J., and Hitchcock-DeGregori, S.E. 2003. Tropomyosin ends determine the stability and functionality of overlap and troponin T complexes. Biophys. J. 84: 3181-3189.

5. Singh, A. and Hitchcock-DeGregori, S.E. 2003. Local destabilization of the tropomyosin coiled coil gives the molecular flexibility required for actin binding. Biochemistry 48:14114-14121.

6. Kostyukova, A.S. and Hitchcock-DeGregori, S.E. Effect of the structure of the N terminus of tropomyosin on tropomodulin function. J. Biol. Chem. 2004, 279:5066-5071.

7. Gupton, S.L. et al. (11 authors). 2005. Cell mitration without a lamellipodium: Translation of actin dynamics into cell movement mediated by tropomyosin. J. Cell Biol. 168: 619-631.

8. Kostyukova, A.S., Rapp, B., Choy, A., Greenfield, NJ and Hitchcock-DeGregori, S.E. 2005. Structural requirements of tropomodulin for tropomyosin binding and actin filament capping. Biochemistry 44:4905-4910.

9. Singh, A., and Hitchcock-DeGregori, S.E. 2007. Tropomyosin’s periods are quasi-equivalent for actin binding but have specific regulatory functions. Biochemistry 46: 14917-14927.

10. Greenfield, N.J., Kotlyanskaya, L. and Hitchcock-DeGregori, S.E. 2009. Structure of the N Terminus of a Non-Muscle α-Tropomyosin in Complex with the C Terminus: Implications for Actin Binding. Biochemistry 48:1272-1283.

D. Research Support



Ongoing Research Support Muscular Dystrophy Association Hitchcock-DeGregori PI 01/01/2008-12/31/2010 Tropomyosin in Health and Disease: Bioinformatics and Biophysical Approaches Bioinformatics approaches will be applied to sequences in the genomic data bases to identify events during phylogeny that lead to tropomyosin as we know it: gene duplication, exon duplication, and to identify functionally important residues by measuring the shifts in evolutionary rates. The results will lead to new, testable hypotheses concerning structure-function relationships in the tropomyosin coiled coil. Role: PI Completed Research Support (last three years) RO1 GM36326 Hitchcock-DeGregori PI 07/01/2003-06/31/2007 Regulation of Contraction in Muscle and Nonmuscle Cells The overall goals of the grant were to determine the structures and dynamics of coiled coil domains of tropomyosin and myosin that are important for function. A major focus was to determine using NMR the atomic resolution structures of the end-to-end overlap complexes of short and long tropomyosin isoforms, and of the striated muscle complex with troponin T, using model peptides. We also tested the hypothesis that localized flexibility of the coiled coil is important for the binding interactions of tropomyosin Role: PI UMDNJ Foundation Hitchcock-DeGregori PI 07/01/2007-06/30/2009 Molecular Mechanism of Regulation of Contraction This was bridge funding for RO1 GM36326. Role: PI Pending Applications NIH (RO1): Deciphering how tropomyosin regulates the actin filament. American Heart Association (Grant-in-Aid): Control of actin function and dynamics by tropomyosin: an integrated cellular, genetic and biochemical approach

Principal Investigator/Program Director (Last, First, Middle): Irvine, Kenneth D.




NAME Kenneth D. Irvine eRA COMMONS USER NAME kirvine




Williams College, Williamstown MA B.A. 1981-1985 Chemistry Stanford University, Stanford CA PhD 1985-1991 Biochemistry Princeton University, Princeton NJ 1991-1995 Developmental Biol.

Please refer to the application instructions in order to complete sections A, B, and C of the Biographical Sketch. Research Positions & Professional Experience: 1984-1985 Undergraduate Thesis, Williams College, "Site-specific mutagenesis of sequences implicated in

splicing of the Tetrahymena thermophila large rRNA precursor," John M. Burke, Advisor. 1985-1991 Ph.D. Thesis Stanford University, "Regulation of expression of the Drosophila homeotic gene

Ultrabithorax", David S. Hogness, Advisor. 1991-1995 Post-doctoral Fellow, Princeton University, Eric Wieschaus, Advisor 1995 - 2001 Assistant Professor, 2001 - 2006 Associate Professor, 2006 - Professor, Waksman Institute and Department of Molecular Biology and Biochemistry, Rutgers

University, Piscataway NJ. 2000- 2004 Assistant Investigator, 2005- Investigator, Howard Hughes Medical Institute

Awards and Other Professional Activities: 1984&1985 Magna cum laude, John Sabian Adriance Prize in Chemistry, Phi Beta Kappa, Sigma Xi, American Chemical Society Award 1986-1989 NSF Graduate Fellowship 1991-1994 Helen Hay Whitney Foundation Postdoctoral Fellowship 1994-1995 New Jersey Commission on Cancer Research Postdoctoral Fellowship 1996-1997 American Cancer Society Junior Faculty Research Award 1997-2003 Ad hoc reviewer for grants submitted to NSF 2000 Appointed as an Assistant Investigator of the Howard Hughes Medical Institute 2001 Rutgers Board of Trustees Research Fellowship for Scholarly Excellence 2004 ad hoc member of ACS Development, Differentiation, and Cancer Study Section 2005-present Associate Editor, Developmental Dynamics 2009 co-Editor, Current Opinion in Genetics & Development Aug 09 Issue 2003-2008 Member NIH Study Section, Development-1 2008-2009 Chair NIH Study Section, Development-1 Publications: 1. Burke, J.M., Irvine, K.D., Kaneko, K.J., Kerker, B.J., Oettgen, A.B., Tierney, W.M., Williamson, C.L., Zaug, A.J. and Cech. T.R. 1986. Role of conserved sequence elements 9L and 2 in self-splicing of the Tetrahymena ribosomal RNA precursor. Cell 45: 167-176. 2. Irvine, K.D., Helfand, S.L. and Hogness, D.S. 1991. The large upstream control region of the Drosophila homeotic gene Ultrabithorax. Development 111: 407-424. 3. Irvine, K.D., Botas, J., Jha, S., Mann, R., and Hogness, D.S. 1993. Negative autoregulation by Ultrabithorax controls the level and pattern of its expression. Development 117: 387-399.


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4. Irvine, K.D. and Wieschaus, E. 1994. Cell intercalation during Drosophila germband extension and its regulation by pair-rule segmentation genes. Development 120: 827-841. 5. Irvine, K.D. and Wieschaus, E. 1994. fringe, a boundary-specific signaling molecule, mediates interactions between dorsal and ventral cells during Drosophila wing development. Cell 79: 595-606. 6. Kim, J., Irvine, K.D., and Carroll, S.B. 1995. Cell recognition, signal induction, and symmetrical gene activation at the dorsal/ventral boundary of the developing Drosophila wing. Cell 82: 795-802. 7. Johnston, S.H., Rauskolb, C., Wilson, R., Prabhakaran, B., Irvine, K.D., Vogt, T.F. 1997. A family of mammalian Fringe genes implicated in boundary determination and the Notch pathway, Development 124, 2245-2254. 8. Panin, V.M., Papayannopoulos, V., Wilson, R., and Irvine, K.D. 1997. Fringe modulates Notch-ligand interactions. Nature 387, 908-913. 9. Irvine, K.D. and Vogt, T.F. 1997. Dorsal-ventral signaling in limb development. Curr Opin Cell Biol. 9, 867-876. 10. Papayannopoulos, V. P., Tomlinson, A., Panin, V. M., Rauskolb, C. and Irvine, K. D. 1998. Dorsal-ventral signaling in the Drosophila eye. Science 281, 2031-2034. 11. Panin, V.M. and Irvine, K. D. 1998. Modulators of Notch signaling. Sem. Cell & Dev. Biol. 9, 609-617. 12. Simmonds, A. J., Liu, X., Soanes, K.H., Krause, H.M., Irvine, K.D. and Bell, J.B. 1998. Molecular interactions between Vestigial and Scalloped promote wing formation in Drosophila. Genes Dev. 12, 3815-3820. 13. Rauskolb, C. and Irvine, K.D. 1999. Notch-mediated segmentation and growth control of the Drosophila leg. Dev. Biol. 210, 339-350. 14. Irvine, K. D. 1999. Fringe, Notch, and making developmental boundaries Curr Opin Genet & Dev. 9, 434-441. 15. Rauskolb, C., Correia, T. and Irvine, K.D. 1999. Fringe-dependent separation of dorsal and ventral cells in the Drosophila wing. Nature, 401, 476-480. 16. Moloney, D. J., Panin, V. M., Johnston, S. H., Chen, J., Shao, L., Wilson, R., Wang, Y., Stanley, P., Irvine, K. D. Haltiwanger, R. S. and Vogt, T. F. 2000. Fringe is a glycosyltransferase that modifies Notch. Nature, 406, 369-375. 17. Liu, X., Grammont, M. and Irvine, K. D. 2000. Roles for scalloped and vestigial in regulating cell affinity and interactions between the wing blade and the wing hinge. Dev. Biol., 228. 287-303. 18. Grammont, M. and Irvine, K. D. 2001. Fringe and Notch specify polar cell fate during Drosophila oogenesis, Development, 128, 2243-2253. 19. Irvine, K. D. and Rauskolb, C. R. Boundaries in development: formation and function. 2001. Ann Reviews Cell & Dev. Biol., 17, 189-214. 20. Panin, V.M., Shao, L., Lei, L., Moloney, D.J., Irvine, K.D., and Haltiwanger, R.S. 2002. Notch ligands are substrates for Protein O-fucosyltransferase-1 and Fringe. J. Biol. Chem., 277, 29945-29952. 21. Grammont, M. and Irvine, K.D. 2002. Organizer activity of the polar cells during Drosophila oogenesis. Development, 129, 5131-5140. 22. Nakamura, Y., Haines, N., Chen, J., Okajima, T., Furukawa, K., Urano, T., Stanley, P., Irvine, K.D., and Furukawa, K. 2002. Identification of a Drosophila gene encoding xylosylprotein ß4-galactosyltransferase that is essential for the synthesis of glycosaminoglycans and for morphogenesis. J. Biol. Chem., 277, 46280-46288. 23. Okajima, T. and Irvine, K.D. 2002. Regulation of Notch signaling by O-linked fucose. Cell, 111, 893-904. 24. Li, Y. Lei, L., Irvine, K.D. and Baker, N.E. 2003. Notch activity in neural cells triggered by a mutant allele with altered glycosylation. Development, 130, 2829-2840. 25. Correia, T., Papayannopoulos, V., Panin, V., Woronoff, P., Jiang, J., Vogt T.F. and Irvine, K.D. 2003. Molecular genetic analysis of the glycosyltransferase Fringe in Drosophila. PNAS, 100, 6404-6409. 26. Okajima, T., Xu, A. and Irvine, K.D. 2003. Modulation of Notch-ligand binding by Protein O-fucosyltransferase 1 and Fringe. J. Biol. Chem. 278, 42340-50. 27. Haines, N. and Irvine, K.D. 2003. Glycosylation regulates the Notch signaling pathway. Nature Rev MCB, 4, 786-797. 28. Lei, L., Xu, A., Panin, V. and Irvine, K. D. 2003. An O-fucose site in the ligand binding domain inhibits Notch activation, Development 130, 6411-6421. 29. Koles, K. Irvine, K. D., Panin, V. M. 2004. Functional characterization of the Drosophila Sialyltransferase. J. Biol. Chem. 279, 4346-57.



30. Cho, E. and Irvine, K.D. 2004. Action of fat, four-jointed, dachsous and dachs in distal-to-proximal wing signaling. Development, 131, 4489-4500. 31. Haines, N. and Irvine, K.D. 2005. Functional analysis of Drosophila N-Acetlygalactosaminyltransferases. Glycobiology, 15, 335-346. 32. Okajima, T., Xu, A., Lei, L. and Irvine, K.D. 2005. Chaperone Activity of Protein O-fucosyltransferase 1 Promotes Notch Receptor Folding. Science 30, 1599-1603. 33. Xu, A., Lei, L. and Irvine, K.D. 2005. Regions of Notch that contribute to ligand binding and the modulatory influence of Fringe. J. Biol. Chem., 280, 30158-30165. 34. Major, R. and Irvine, K.D. 2005. Influence of Notch on dorsal-ventral compartmentalization and actin organization in the Drosophila wing. Development, 132, 3823-3833. 35. Rogulja, D. and Irvine, K.D. 2005 Regulation of cell proliferation by a morphogen gradient. Cell 123, 449-461. 36. Mao, Y., Rauskolb, C., Cho, E., Hu, W.-L., Hayter, H., Minihan, G., Katz, F.N., and Irvine, K.D. 2006. Dachs, an unconventional myosin that functions downstream of Fat to regulate growth, affinity and gene expression in Drosophila. Development 133, 2539-2551 . 37. Cho, E., Feng, Y., Rauskolb, C., Maitra, S., Fehon, R., and Irvine, K.D. 2006. Delineation of a Fat tumor suppressor pathway. Nature Genetics 38, 1142-1150. 38. Major, R. and Irvine, K.D. 2006. Localization and requirement for Myosin II at the dorsal-ventral compartment boundary of the Drosophila wing. Dev. Dyn. 235, 3051-3058. 39. Stolz, A., Haines, N., Pich, A., Irvine, K. D., Hokke, C. H., Deelder, A. M., Gerardy-Schahn, R., Wuhrer, M. and Bakker, H. 2007. Distinct contributions of β4GalNAcTA and β4GalNAcTB to Drosophila glycosphingolipid biosynthesis. Glycoconjugate J., DOI 10.1007/s10719-007-9069-5. 40. Xu, A. and Haines, N., Dlugosz, M., Rana, N.A., Takeuchi, H. Haltiwanger, R.S., and Irvine, K.D. 2007. In vitro reconstitution of the modulation of Drosophila Notch-ligand binding by Fringe. J. Biol. Chem. 282, 35153-35162. 41. Feng, Y. and Irvine, K.D. 2007. Fat and expanded act in parallel to regulate growth through Warts. Proc. Nat. Acad. Sci. USA, 104, 20362-20367. 42. Okajima, T., Reddy, B.V.V.G., Matsuda, T. and Irvine, K.D. 2008. Contributions of chaperone and enzyme activities of O-fucosyltransferase 1 to Notch signaling. BMC Biology.6, 1. 43. Irvine, K.D. 2008. A Notch sweeter. Cell. 132, 177-179. 44. Oh, H., Irvine, K.D. 2008. in vivo regulation of Yorkie phosphorylation and localization. Development 135, 1081-1088. 45. Ishikawa, H.O., Takeuchi, H., Haltiwanger, R.S. and Irvine, K.D. 2008. Four-jointed is a Golgi kinase that phosphorylates a subset of cadherin domains. Science 321, 401-404. 46. Rogulja, D. Rauskolb, C. and Irvine, K.D. 2008 Morphogen control of wing growth through the Fat signaling pathway. Developmental Cell, 15, 309-321. 47. Reddy, B.V.V.G. and Irvine, K.D. 2008. The Fat ands Warts signaling pathways: new insights into their regulation, mechanism, and conservation. Development, 135, 2827-2838. 48. Lin, Y., Reddy, B.V.V.G., and Irvine, K.D. 2008. Requirement for a core 1 galactosyltransferase in the Drosophila nervous system. Dev. Dyn. 237, 3703-3714. 49. Oh, H., Irvine, K.D. 2009. in vivo analysis of Yorkie phosphorylation sites. Oncogene 28, 1916-1927. 50) Feng, Y. and Irvine, K.D. 2009. Processing and Phosphorylation of the Fat receptor. Proc. Nat. Acad. Sci. USA, 106, 11989-11994. 51) Mao, Y., Kucuck, B., Irvine K.D. 2009 Drosophila lowfat, a novel modulator of Fat signaling. Development 136, 3223-3233. 52) Anderson, K. and Irvine, K. 2009. Developmental biology moves forward in the 21st century. Curr. Opin. Genet. & Dev. 19, 1-3. 53) Oh, H., Reddy, B.V.V.G. and Irvine, K.D. 2009. Phosphorylation-independent repression of Yorkie in Fat-Hippo signaling. Dev. Biol. 335, 188-197. 54) Reddy, B.V.V.G., Rauskolb, C., Irvine, K.D. 2010. Regulation of the proliferation and differentiation of Drosophila optic neuroepithelia. Submitted (in revision) 55) Simon, M.A., Xu, A., Ishikawa, H.O. and Irvine, K.D. 2010. Modulation of Fat-Dachsous binding by the cadherin domain kinase Four-jointed. Submitted (in revision) 56) Oh, H., Irvine, K.D. 2010. Yorkie: the final destination of Hippo signaling. submitted



57) Kucuk, B. and Irvine, K.D. 2010. Hippo signaling mediates intestinal regeneration by controlling stem cell proliferation. submitted

Research Support Howard Hughes Medical Institute Investigatorship (renewed through 8/31/10). Provides salary of PI and $645,618 (FY2009) in support for salary and other research costs. * HHMI does not allow individual support levels to be publicized, but it can be included in an aggregate total. NIH R01 GM 078620-01 to -04 Regulation of Growth by the Fat Signaling Pathway 5/1/07 - 4/30/11 $170,000 direct costs support.


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NAME Terri Goss Kinzy, Ph.D. eRA COMMONS USER NAME kinzytg




The University of Akron, Akron, OH B.S. 1980-1985 Chemistry Case Western Reserve Univ., Cleveland Ph.D. 1987-1991 Biochemistry Carnegie Mellon University, Pittsburgh, PA Post-doc 1991-1995 Molecular Genetics

A. POSITIONS AND HONORS: Professor Dept. of Molecular Genetics, Microbiology & Immunology 2004 – present Dept. of Pediatrics 2007 - present Associate Professor UMDNJ-Robert Wood Johnson Medical School Piscataway, NJ 2001 – 2004 Assistant Professor 1995 – 2001 Executive Director, RWJMS DNA Sequencing Laboratory 1998 - present Director RWJMS, Rutgers University, Princeton University MD/PhD Program 2005 – present Sr. Associate Dean UMDNJ Graduate School of Biomedical Sciences 2007 – present HONORS: 2010 Theme organizer, ASBMB Annual Meeting 2009 Session chair, EMBL Protein Synthesis and Translational Control Meeting 2008 Co-organizer, Cold Spring Harbor Translational Control Meeting 2007 Co-organizer, AAMC GREAT Group MD-PhD Section Annual Meeting 2006 New Jersey Association for Biomedical Research Outstanding Mentor Award 2005 R. Walter Schlesinger Basic Science Mentoring Award 2004 Woman of the Year in Medicine, Somerset County NJ 2003 Hedwig van Ameringen Executive Leadership in Academic Medicine Fellow 2002 Compact for Faculty Diversity, Faculty Mentor of the Year 2001 Inducted UMDNJ Master Educator Guild 2001 Invited speaker and session chair, 66th Cold Spring Harbor Symposium: The

Ribosome 2000 Session chair, Cold Spring Harbor Translational Control Meeting 2000-2005 N.S.F. CAREER Award Recipient 1996 Cancer Institute of New Jersey ACS Junior Faculty Research Award SERVICE: 2004-2007 Member: NIH Molecular Genetics-C Study Section 2003-2004 Member: NIH Physiological Chemistry Study Section 2000-2002 Ad Hoc Reviewer: NIH Physiological Chemistry Study Sections 2009-2010 Ad Hoc Reviewer: NIH ZRG K99 and P30 Study Sections B. SELECT PEER-REVIEWED PUBLICATIONS: Anthony, D. D., Kinzy, T. G. and Merrick, W. C. (1990) Affinity Labeling of Eukaryotic Initiation Factor 2 and

Elongation Factor 1 αβγwith GTP Analogs, Arch. Bioc. Biophys., 281, 157-162. PMID: 2383020 Kinzy, T. G. and Merrick, W. C., (1991) Characterization of a Limited Trypsin Digestion Form of Eukaryotic

Elongation Factor 1α, J. Biol. Chem., 266, 4099-4105. PMID: 1999404 Kinzy, T. G., Freeman, J.P., Johnson, A.E. and Merrick, W. C., (1992) A Model for the Aminoacyl-tRNA

Binding Site of Eukaryotic Elongation Factor 1α, J. Biol. Chem., 267, 1623-1632. PMID: 1730707 Hannig, E.M., Cigan, A.M., Freeman, B.A. and Kinzy, T.G., (1993) GCD11, a Negative Regulator of GCN4

Expression, Encodes the γ Subunit of eIF-2 in Yeast, Mol. Cell. Biol., 13, 506-520. PMID: 8417348 Kinzy, T.G., Ripmaster, T.L. and Woolford, J.L. (1994) Multiple Genes Encode the Translation Elongation

Factor 1-γ in Saccharomyces cerevisiae, Nucleic Acids Res. 22, 2703-2707. PMID: 8041634


Kinzy, T.G. and Woolford, J.L.(1995) Increased Expression of Saccharomyces cerevisiae Translation Elongation Factor 1a Bypasses the Lethality of a Null Allele Encoding EF-1β, Genetics 141, 481-489. PMID: 8647386

Asano, K., Kinzy, T.G., Merrick, W.C. and Hershey, J.W.B. (1997) Conservation and Diversity of Eukaryotic Translation Initiation Factor eIF-3, J. Biol. Chem. 272, 1101-1109. PMID: 8995409

Dinman, J.D. and Kinzy, T.G. (1997) Translational Misreading: Mutations in Translation Elongation Factor 1α Differentially Affect Programmed Ribosomal Frameshifting and Drug Sensitivity, RNA 3, 870-881. Carr-Schmid, A., Valente, L., Loik, V.I., Williams, T., Starita, L.M. and Kinzy, T.G. (1999) Mutations in Elongation Factor 1β, a Guanine Nucleotide Exchange Factor, Enhance Translational Fidelity, Mol. Cell. Biol. 19, 5257-5266. PMID: 9257646

Carr-Schmid, A., Durko, N., Cavallius, J. Merrick, W.C. and Kinzy, T.G. (1999) Mutations in a GTP-Binding Motif of eEF1A Reduce Both Translational Fidelity And The Requirement For Nucleotide Exchange, J. Biol. Chem.274, 30297-30302. PMID: 10514524

Kinzy, T.G. and Goldman, E. (2000) Non-translational Functions Of Components Of The Translational Apparatus, in Translational Control, M. Mathews, J.W.B. Hershey and N. Sonenberg, eds. Cold Spring Harbor Laboratory Press, 993-997.

Andersen, G.R. Pedersen, L., Valente, L., Chatterjee, I., Kinzy, T.G., Kjeldegard, M. and Nyborg, J. (2000) Structural Basis For Nucleotide Exchange And Competition With tRNA In The Yeast Elongation Factor Complex eEF1A:eEF1Bα Molecular Cell. 6, 1261-1266. PMID: 11106763

Pedersen, L. P., Andersen, G. R., Knudsen, C.R., Kinzy, T.G. and Nyborg, J. (2001) Crystallization of the Yeast Elongation Factor Complex eEF1A:eEF1Bα, Acta Crystallogr. D Biol. Crystallogr. 57(Pt 1), 159-161. PMID: 11134944

Munshi, R., Kandl, K.A., Carr-Schmid, A., Whitacre, J.L., Adams, A.E.M., and Kinzy, T.G. (2001) Overexpression of Translation Elongation Factor 1A Affects The Organization And Function Of The Actin Cytoskeleton In Yeast, Genetics 157, 1425-1436. PMID: 11290701

Andersen, G.R., Valente, L., Pedersen, L., Kinzy, T.G. and Nyborg, J. (2001) Crystal Structures of Nucleotide Exchange Intermediates In The eEF1A:eEF1Bα Complex, Nature Struct. Biol. 8, 531-534. PMID: 11373622

Carr-Schmid, E., Pfund, C., Craig, E.A., and Kinzy, T.G. (2002) Novel G-protein Complex Whose Requirement Is Linked To The Translational Status Of The Cell, Mol. Cell. Biol. 22, 2564-2574. PMID: 11909951

Jørgensen, R., Carr-Schmid, A., Ortiz, P.A., Kinzy, T.G. and Andersen, G.R. (2002) Purification and Crystallisation Of The Yeast Elongation Factor eEF2, Acta Crystallogr. D58, 712-715. PMID: 11914505

Anand, M., Valente, L., Carr-Schmid, A., Munshi, R., Olarewaju, O., Ortiz, P. and Kinzy, T.G. (2002) Functions of the Translation Elongation Factor 1 in the Yeast Saccharomyces cerevisiae, Symposium on Quantitative Biology, 66, 439-448. PMID: 12762046

Kinzy, T.G., Harger, J.W., Carr-Schmid, A., Kwon, J., Shastry, M., Justice, M., and Dinman, J.D. (2002) New Targets For Antivirals: The Ribosomal A-Site And The Factors That Interact With It, Virology, 300; 60-70. PMID: 12202206

Kandl, K.A., Munshi, R., Ortiz, P.A., Andersen, G.R., Kinzy, T.G., and Adams, A.E.M. (2002) Identification of a Role For Actin In Translational Fidelity In Yeast, Mol. Gen. Genomics, 268; 10-18. PMID: 12242494

Anand, M., Chakraburtty, K., Marton, M., Hinnebusch, A., and Kinzy, T.G. (2003) Functional Interactions Between Yeast Translation Elongation Factors eEF1A and eEF3, J. Biol. Chem, 278; 6985-6991. PMID: 12493761

Jørgensen, R., Ortiz, P.A., Carr-Schmid, A., Nissen, P., Kinzy, T.G. and Andersen, G.R. (2003) Two Crystal Structures Demonstrate Very Large Conformational Changes Of The Eukaryotic Ribosomal Translocase, Nature Struct. Biol,.10; 379-385. PMID: 12692531

Valente, L. and Kinzy, T.G. (2003) Yeast as a Sensor of Factors Affecting The Accuracy Of Protein Synthesis, Cell. Mol. Life Sci., 60; 2115-2130. PMID: 14618259 Pomerening, J.R., Valente, L., Kinzy, T.G., and Jacobs, T.W. (2003) Mutation of a conserved CDK

phosphorylation site converts metazoan Elongation Factor 1Bβ into a replacement for yeast eEF1Bα, Mol. Gen. Genomics, 269; 776-788. PMID: 12898219

Jeppesen, M.G., Ortiz, P.A., Shepard, W., Kinzy, T.G., Nyborg, J. and Andersen, G.R. (2003) The Crystal Structure of the GST-like Domain of Elongation Factor 1Bγ from Saccharomyces cerevisiae, J. Biol. Chem., 278; 47190-47198. PMID: 12972429


Arora S., Yang, J.M., Kinzy, T.G., Utsumi, R., Okamoto, T., Kitayama, T., Ortiz, P.A., Hait, W.N. (2003) Identification and Characterization Of An Inhibitor Of Eukaryotic Elongation Factor 2 Kinase Against Human Cancer Cell Lines, Cancer Res., 63; 6894-6899. PMID: 14583488

Jan, E. Kinzy, T.G. and Sarnow, P. (2003) Divergent RNA Element Supports Initiation, Elongation And Termination In Protein Biosynthesis, Proc. Natl. Acad. Sci. USA,100; 15410-15415. PMID: 14673072

Andersen, C.F., Anand, M., Boesen, T., Van, L.B., Kinzy, T.G. and Andersen, G.R. (2004) Purification and Crystallisation of the Yeast Translation Elongation Factor eEF3, Acta Crystallogr. D Biol. Crystallogr. D60; 1304-1307. PMID: 15213400

Olarewaju, O., Chowdhury, W., Ortiz, P.A., Chatterjee, I., and Kinzy, T.G. (2004) The Translation Elongation Factor, eEF1B Plays a Role in the Oxidative Stress Response Pathway, RNA Biology 1;12-17. PMID: 17179749

Chuang, S-M., Lambertson, D., Chen, L., Anand, M., Kinzy, T. G. and Madura, K. (2005) Proteasome-Mediated Degradation of Co-translationally Damaged Proteins Involves the Translation Elongation Factor eEF1A, Mol. Cell. Biol. 25:403-413. PMID: 15601860

Copeland, H.L. and Kinzy, T.G. (2005) Development and Evaluation of a Peer-Tutoring Program for Graduate Students, Biochem. Mol. Biol. Ed. 33:86-90.

Komar, A.A., Gross, S.R., Barth-Baus, D., Strachan, R., Hensold, J.O., Kinzy, T.G. and Merrick, W.C. (2005) Novel Characteristics of the Biological Properties of the Yeast Saccharomyces cerevisiae Initiation Factor elF2A, J. Biol. Chem. 280:15601-15611. PMID: 15718232

Magazinnik, T., Anand, M., Sattlegger, E., Hinnebusch, A.G., and Kinzy, T.G (2005) Interplay Between GCN2 and GCN4 Expression, Translation Elongation Factor 1 Mutations, and Translational Fidelity in Yeast. Nuc. Acids Res. 33: 4584-4592. PMID: 16100380

Gross, S.R. and Kinzy, T.G. (2005) The Translation Elongation Factor 1A Plays Essential Regulatory Functions in the Organization of Both the Actin Cytoskeleton and Cell Morphology Nature Struct. Mol. Bio. 12:772-778. PMID: 16116436

Ortiz, P.A. and Kinzy, T.G. (2005) Dominant Negative Mutant Phenotypes and the Regulation of Translation Elongation Factor 2 Levels in Yeast. Nucl. Acids Res. 33:5740-5748. PMID: 16214807

Chatterjee, I., Gross, S.R., Kinzy, T.G. and Chen, K.Y. (2006) Rapid Depletion of Mutant Eukaryotic Initiation Factor 5A at Restrictive Temperature Reveals Connections to Actin Cytoskeleton and Cell Cycle Progression. Mol. Gen. Genomics. 275:264-276. PMID: 16408210

Pittman, Y., Valente, L., Jeppesen, M.G., Andersen, G.R., Patel, S. and Kinzy, T.G. (2006) Mg+2 and a Key Lysine Residue Modulate Guanine Nucleotide Exchange by Eukaryotic Translation Elongation Factor 1Bα. J. Biol. Chem. 281:19457-19468. PMID: 16675455

Andersen, C.B.F., Becker, T., Blau, M., Anand, M., Halic, M., Balar, B., Mielke, T., Boesen, T., Petersen, J.S., Spahn, C.M.T., Kinzy, T.G., Andersen, G.R. and Beckmann, R. (2006) Structure of eEF3 and the mechanism of transfer RNA release from the E-site. Nature, 443:663-668. PMID: 16929303

Ozturk S., Vishnu M.R., Olarewaju O., Starita L.M., Masison D.C. and Kinzy T.G. (2006) Unique classes of mutations in the Saccharomyces cerevisiae G-protein translation elongation factor 1A suppress the requirement for guanine nucleotide exchange, Genetics, 174:651-663. PMID: 16951075

Ortiz, P.A., Ulloque, R., Zheng, H., and Kinzy, T.G. (2006) Eukaryotic translation elongation factor 2 anticodon mimicry domain mutants affect fidelity and diphtheria toxin resistance. J. Biol. Chem. 281:32639-32648. PMID: 16950777

Anand, M., Balar, B., Ulloque, R., Gross, S.R. and Kinzy, T.G. (2006) Domain and nucleotide dependence of the interaction between Saccharomyces cerevisiae translation elongation factors 3 and 1A. J. Biol. Chem. 281:32318-32326. PMID: 16954224

Taylor, D., Frank, J. and Kinzy, T.G. (2006) Structure and Function of the Eukaryotic Ribosome and Elongation Factors, in Translational Control of Gene Expression, N. Sonenberg, J.W.B. Hershey and, M. Mathews, eds. Cold Spring Harbor Laboratory Press. 59-85.

Gross, S.R. and Kinzy, T.G. (2007) Improper organization of the actin cytoskeleton affects protein synthesis at initiation. Mol. Cell. Biol. 27: 1974-1989. PMID: 17178834

Cai, Y.C., So1, C.K., Nie1,A.Y., Song, Y., Yang, G., Wang, L., Zhao, X., Kinzy, T.G., and Yang, C.S. (2007) Characterization of genetic alteration patterns in human esophageal squamous cell carcinoma using selected microsatellite markers spanning multiple loci. Intern. J. Oncology. 30: 1059-67. PMID: 17390007


Hampsey, M. and Kinzy, T.G. (2007) Synchronicity: Policing multiple aspect of gene expression by Ctk1. Genes and Development, 21:1288-1291. PMID: 17545464

Plant, E.P., Nguyen, P., Quesinberry, J.T., Nguyen, T., Pittman, Y.R., Kinzy, T.G., and Dinman, J.D. (2007) Differential effects of ribosome and translation factor mutants on near- and non-cognate missense codon suppression in yeast. PloS One. 6:e517. 39. PMID: 17565370

Galkin, O., Bentley, A.A., Gupta, S., Compton, B., Mazumder, B., Kinzy, T.G., Merrick, W.C., Hatzoglou, M., Pestova, T.V., Hellen, C.U.T. And Komar, A.A. (2007) Roles of the negatively charged N-terminal extension of Saccharomyces cerevisiae ribosomal protein S5 revealed by characterization of a yeast strain containing human ribosomal protein S5. RNA. 13:2116-28. PMID: 17901157

Gromadski, K.B., Schümmer, T., Strømgaard, A., Knudsen, C.R., Kinzy, T.G., and Rodnina, M.V. (2007) Kinetics of the Interactions between Yeast Elongation Factors 1A and 1B, Guanine Nucleotides, and Aminoacyl-tRNA. J. Biol. Chem. 282:35629-37. PMID: 17925388

Kinzy, T.G., Chang, K., Davila, J., Defren, J., DeStefano, L., Donovan, J., Esposito, A., Hurley, J., Irizarry Barreto, P., Roy, R., Soto, A., Valentin, A., Ysla, R., Copeland, H.L. and Copeland, P.R. (2007) A Birth-to-Death View of mRNA From the RNA Recognition Motif Perspective, Biochem. Mol. Biol. Ed, 36:1-8.

Tash, J.S., Chakrasali, R., Jakkaraj, S.R., Hughes, J., Smith, S.K., Hornbaker, K., Heckert, L.L., Ozturk, S.B., Hadden, M.K., Kinzy, T.G., Blagg, B.S.J., Georg, G.I. (2008) Gamendazole, an orally active indazole carboxylic acid male contraceptive agent, targets HSP-90, eEF1A, and stimulates IL-1 transcription in Sertoli cells. Biol Reprod. 78:1139-52. PMID: 18218611

Ozturk, S. and Kinzy, T.G. (2008) Guanine nucleotide exchange factor independence of the G-protein eEF1A through novel mutant forms and biochemical properties. J. Biol. Chem. 283:23244-53 PMID: 18562321

Seitomer, E., Balar, B., He, D., Copeland, P.R., and Kinzy, T.G. (2008) Analysis of Saccharomyces cerevisiae Null Allele Strains Identifies a Larger Role For DNA Damage Verses Oxidative Stress Pathways in Reduced Growth in Selenium. Molecular Nutrition and Food Research 52:1305-15 PMID: 18496816

Bockhorn, J., Balar, B., Seitomer, E., Copeland, P.R., and Kinzy, T.G. (2008) Genome wide screen of Saccharomyces cerevisiae null allele strains identifies genes involved in selenomethionine resistance. P.N.A.S. 105:17682-17687 PMID: 19004804.

Langhammer , C.G. Garg, K., Neubauer, J.A., Rosenthal, S. and Kinzy, T.G. (2009) Medical Student Research Exposure via a Series of Modular Research Programs, J. Invest. Med. 57:11-17 PMID: 19092679.

Pittman, Y.R., Kandl, K., Lewis, M., Valente, L, and Kinzy, T.G. (2009) Coordination of eEF1A function in actin organization and translation elongation by the guanine nucleotide exchange factor eEF1Bα. J. Biol. Chem. 284:4739-4747 PMID: 19095653.

Li, Z., Pogany, J., Panavas, T., Xu, K., Esposito, A., Kinzy, T.G. and Nagy, P. (2009) Translation Elongation Factor 1A is a component of the tombusvirus replicase complex and affects the stability of the p33 replication co-factor. Virology 385:245-260 PMID: 19131084.

Dinman, J.D and Kinzy, T.G. (2009) Expanding The Ribosomal Universe, Structure 17:1547-1548. NIHMS166049.

Fan Y., Schlierf M., Cuervo Gaspar A., Dreux C., Kpebe A., Chaney L., Mathieu A., Hitte C., Gr Eacutemy O., Sarot E., Horn M., Zhao Y., Kinzy T.G., and Rabinow L. (2010) Drosophila Translational Elongation Factor-1γ is Modified in Response to DOA Kinase Activity and is Essential For Cellular Viability. Genetics 184:141-154. PMID: 19841092.

.

Principal Investigator/Program Director: Kinzy, Terri Goss

PHS 398/2590 (Rev. 04/06) Page _____ Other Support Format Page

KINZY, T. G.

ACTIVE RO1 GM57483 (Kinzy) 8/1/98-11/30/2011 3.0 Cal National Institutes of Health $243,000 Regulators of Translation Elongation Factor eEF1A This award determines mechanism of action of the Translation Elongation Factor eEF1A. Mutational analysis is used to dissect critical residues for function in vivo and in vitro and the interaction with the ribosome and Translation Elongation Factor eEF3.

OVERLAP None

R21 AI076245-01A1 Kinzy) 4/1/09 - 3/31/11 0.6 Cal National Institutes of Health $125,000 Mechanism of Translation Elongation Factor 2 Inhibition by Bacterial Toxins OVERLAP None U54 HD055763 (Tash P.I., Kinzy P.I. of Subcontract) 3/1/07 - 2/28/12 0.6 Cal National Institutes of Health $62,242 Interdisciplinary Center for Male Contraceptive Research and Drug Development This award determines mechanism of action of new lead compounds for male contraceptives targeting Translation Elongation Factor eEF1A.

OVERLAP None RO1 GM57483-S1 (ARRA) 7/15/09 – 6/30/2011 0.6 Cal National Institutes of Health $120,000 Regulators of Translation Elongation Factor EF-1α This award is a supplement focused on post transcriptional control analysis of Translation Elongation Factor eEF1A and actin related mutants.

OVERLAP None

Konsolaki, M.

1

BIOGRAPHICAL SKETCH

NAME Konsolaki, Mary Ph.D.

POSITION TITLE Associate Research Professor

EDUCATION/TRAINING



University of Athens, Greece Diploma (BS equiv) 1981-1986 Biology

University of Crete, Greece Ph.D. 1986-1991 Molecular Biology

Harvard University Visiting Grad. Stud. 1987-1991 Molecular Biology

Princeton University Postdoctoral Fellow 1991-1998 Developmental Biology

A. Positions and Honors. Positions 2004- Associate Research Professor, Department of Genetics, Rutgers The State University of New Jersey 2002-2004 Senior scientist III and Program Head, Novartis Institutes for Biomedical Research 1998-2002 Senior scientist II, Novartis Institutes for Biomedical Research Awards 2005-2006 Focused Giving Program, Johnson & Johnson “Setting New Directions in Science and Technology” 1996–1997 Advanced Research Fellowship from the Governor’s Council on the Prevention of Mental Retardation and Developmental Disabilities, NJ Dept. of Human Services 1993–1996 American Cancer Society (ACS) postdoctoral fellowship 1993–1996 Public Health Service (NIH) individual National Research Service Award (declined) 1993–1996 Fonds de la Recherche en Sante du Quebec, Bourse de Formation Postdoctoral (declined) 1986–1991 Predoctoral scholarship, Institute of Molecular Biology and Biotechnology, Research Center of Crete, Greece Professional activities 2002-2003 Leading at the Frontline - Novartis Managers Program 1999-2000 Novartis Research Productivity Initiative Committee 1999-2003 Graduate Student Admissions Committee and Mentor, Novartis/Dept. of Microbiology and Molecular Genetics, UMDNJ-RWJMS joint graduate program. Rutgers University Service 2004-present Member, Graduate Program in Molecular Biosciences, Rutgers-UMDNJ joint program 2004-2009 Research track peer evaluation FESI Committee, Dept. of Genetics, Rutgers U. (elected) 2005-2006 Genetics Dept. research track faculty re-appointment committee 2005-2009 Genetics Dept. tenure track faculty recruitment committee 2005-present Genetics Dept. annual retreat committee 2005-present Genetics Dept. Undergraduate Honors Day awards committee 2006-2007 Genetics Dept. reading committee for tenure evaluation

Konsolaki, M.

2

Professional Memberships 2005- Member, Society for Neuroscience 2004- Member, New York Academy of Sciences 1998- Member, American Association for the Advancement of Sciences 1998- Member, Genetics Society of America

B. Selected peer-reviewed publications (in chronological order). 1. Psaras, G.K. and Konsolaki, M. (1986). The annual rhythm of cambial activity in four subshrubs

common in phryganic formations of Greece. Israel J Botany 35, 35-9 2. Konsolaki, M., Komitopoulou, K., Tolias, P.P., King, D.L., Swimmer, C. and Kafatos, F.C. (1990). The

chorion genes of the medfly, Ceratitis capitata: I. Structural and regulatory conservation of the s36 gene relative to two Drosophila species. Nucl. Acids Res. 18, 1731-1737.

3. Tolias, P.P., Konsolaki, M., Komitopoulou, K. and Kafatos, F.C. (1990). The chorion genes of the medfly, Ceratitis capitata: II. Characterization of three novel cDNA clones obtained by differential screening of an ovarian library. Dev. Biol. 140, 105-112.

4. Zacharopoulou, A., Frisardi, M., Savakis, C., Robinson, A., Tolias, P. P., Konsolaki, M., Komitopoulou, K. and Kafatos, F. C. (1991). The genome of the Mediterranean fruitfly Ceratitis capitata: Localization of molecular markers by in situ hybridization to salivary gland poletene chromosomes. Chromosoma 101, 448-455.

5. Aggeli, A., Hamodrakas, S.J., Komitopoulou, K. and Konsolaki, M. (1991) Tandemly repeating peptide motifs and their secondary structure in Ceratitis capitata eggshell proteins Ccs36 and Ccs38. Int. J. Biol. Macromol. 13, 307-316.

6. Konsolaki, M., Sanicola, M., Kozlova, T., Liu, V., Arca, B., Savakis, C., Gelbart, W. and Kafatos, F.C. (1992). FLP- mediated intermolecular recombination in the cytoplasm of Drosophila embryos. The New Biologist 4, 551-557.

7. Tolias, P. P., Konsolaki, M., Halfon, M. S., Stroumbakis, N. and Kafatos, F. C. (1993) Elements controlling follicular expression of the s36 chorion gene during Drosophila oogenesis. Molecular and Cellular Biology 13, 5898-5906.

8. Vlachou, D., Konsolaki, M., Tolias, P., Kafatos, F. and Komitopoulou, K. (1997). The autosomal chorion locus of the medfly Ceratitis capitata I. Conserved synteny, amplification and tissue specificity but sequence divergence and altered temporal regulation. Genetics 147 (4),1829-1842.

9. Konsolaki, M. and Schupbach, T. (1998) Windbeutel, a gene required for dorso-ventral patterning in Drosophila, encodes a protein that has homologies to vertebrate proteins of the endoplasmic reticulum. Genes and Development 12(1): 120-131.

10. Sen, J., Goltz, J.S., Konsolaki, M., Schupbach, T. and Stein D. (2000). Windbeutel is required for function and correct subcellular localization of the Drosophila patterning protein Pipe. Development 127, 5541-550

11. Konsolaki, M. and Cohen, D. (2004). Targets for Alzheimers: lessons learnt from flies (review article). Drug Discovery Today: TARGETS 3, 64-70.

12. Iijima, K., Liu, H-P., Chiang, A-S., Hearn, S.A., Konsolaki, M. and Zhong, Y. (2004). Dissecting the pathological effects of human A 40 and A 42 in Drosophila: A potential model for Alzheimer's disease. Proc. Natl. Acad. Sci. USA 101, 6623-6628.

13. Finelli, A., Kelkar, A., Song, H-J., Yang, H. and Konsolaki, M. (2004). Alzheimer's Aβ42 age-related toxicity can be suppressed by the metalloprotease neprilysin in Drosophila melanogaster neurons. Mol. Cell. Neurosci. 26, 365-75.

Konsolaki, M.

3

14. Cao, W., Song, H-J., Gangi, T., Kelkar, A., Antani, I., Garza, D., and Konsolaki, M. (2008). Identification of novel genes that modify phenotypes induced by Alzheimer's beta amyloid overexpression in Drosophila. Genetics 178(3):1457-71. 15. Tan, L., Schedl, P., Song, H-J., Garza, D. and Konsolaki, M. (2008). The Toll NFkB signaling pathway mediates the neuropathological effects of the human Alzheimer’s Ab42 polypeptide in Drosophila. PLoS ONE 3(12):e3966. 16. van de Hoef, D., Hughes, J., Livne-Bar, I., Garza, D., Konsolaki, M. and Boulianne, G.L. (2009). Identifying Genes that Interact with Drosophila Presenilin and Amyloid Precursor Protein. Genesis 47(4):246-60 17. Sanokawa-Akakura, R., Cao W., Allan, K., Patel, K., Ganesh, A., Heiman, G., Burke, R., Kemp, F., Bodgen, J., Camakaris, J., Birge, RB., and Konsolaki, M. (2010). Regulation of Alzheimer’s amyloid beta toxicity by the high molecular weight immunophilin FKbp52 and copper homeostasis. PLoS ONE 5(1): e8626. doi:10.1371/journal.pone.0008626. Patents: 1. Transgenic Drosophila melanogaster expressing Alzheimer's beta-amyloid. Regular US application case # 4-31612A; PCT Application No. EP01/11345 IDS filed 3/20/02 2. Modifiers of Abeta phenotypes as targets for developing therapies for Alzheimer’s. Provisional application # 4-33424 3. Diagnostic Assays for Alzheimer's Disease Provisional application # 4-33715P1 C. Research Support (past and current)

Intracellular Therapies Inc./Rockefeller University – Research Collaborative agreement on “Analysis of gamma-secretase processing of Alzheimer’s APP protein” Apr 2009-Jan 2010. PI: Konsolaki

American Health Assistance Foundation Research Grant – Alzheimer’s Disease Research 2005-2007 NCE Mar 2008 “Modifiers of Abeta toxicity in Drosophila” PI: Konsolaki Focused Giving Program Award, Johnson & Johnson Corporate Office of Science and Technology 2005-2007 NCE Jun 2008 “Pathway analysis of Alzheimer’s Abeta-associated toxicity” PI: Konsolaki Novartis Institutes for Biomedical Research Collaborative Agreement 2005-2007 PI: Konsolaki Start-up funds from the Genetics Department, Rutgers University

BIOGRAPHICAL SKETCH

NAME Kramer, Sunita Gupta eRA COMMONS USER NAME kramersg

POSITION TITLE Associate Professor Department of Pathology & Laboratory Medicine

EDUCATION/TRAINING


Franklin and Marshall College B.S. 1988-1992 Biology State University of New York at Stony Brook Ph.D. 1992-1998 Cell & Dev. Biology Marine Biological Laboratory, Woods Hole, MA 1993 Embryology University of California at Berkeley Postdoctoral 1998-2002 Cell Biology

A. Positions and Honors Positions and Employment 1990-1992 Undergraduate Research Assistant, Department of Biology, Franklin and Marshall College, Laboratory of Dr. Richard A. Fluck 1992-1998 Graduate Research Assistant, Department of Molecular and Cellular Biology, State University of New York at Stony Brook, Laboratory of Dr. J. Peter Gergen 1998-2002 Postdoctoral Research Fellow, Department of Neuroscience, University of California at Berkeley, in the laboratory of Dr. Corey S. Goodman 2001-2002 Visiting Biology Lecturer, Vista Community College, Berkeley, CA 2003-2009 Assistant Professor, Department of Pathology and Laboratory Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School 2006-present Associate member of the Child Health Institute of New Jersey 2008-present Member of the Cancer Institute of New Jersey 2009-present Associate Professor, Department of Pathology and Laboratory Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School Professional Memberships 1996- Genetics Society of America 1995- Society for Developmental Biology 2005- American Society for Cell Biology 2008- North American Vascular Biology Association Honors 1990 Hackman Scholar Award for Undergraduate Research 1993 C. Lalor Burdick Scholarship, Marine Biological Laboratory 1996 Sigma Xi Travel Award 1998 Best Poster Award, Society for Developmental Biology 1999 Spinal Cord Research Foundation Postdoctoral Fellowship 2003 Foundation of UMDNJ Faculty Research Award 2004 American Heart Association Scientist Development Grant 2005 Compact for Faculty Diversity Faculty Mentor of the Year Award 2006/2008 National Institutes of Health Pediatric Loan Repayment Award B. Selected peer-reviewed publications

PHS 398/2590 (Rev. 09/04, Reissued 4/2006) Page 2 Continuation Format Page

Abraham, V.C., Gupta, S. and Fluck, R.A. 1993. Ooplasmic segregation in the medaka (Oryzias latipes) egg. Biol. Bull. 184: 115-124.

Tsai, C.C., Kramer, S.G., and Gergen, J.P. 1998. The pair rule gene runt restricts orthodenticle expression to the presumptive head of the Drosophila embryo. Dev. Genet. 23(1): 35-44.

Kramer, S.G., Jinks, T.M., Schedl, P. and Gergen, J.P. 1999. Direct activation of Sex-lethal transcription by the Drosophila Runt protein. Development 126:191-200.

Tracey W.D., Ning, X., Klingler, M., Kramer S.G., and Gergen, J.P. 2000. Quantitative analysis of gene function in the Drosophila embryo. Genetics 154:273-284.

Kramer, S.G., Kidd T., Simpson, J.S., and Goodman C.S. 2001. Switching repulsion to attraction: changing responses to Slit during transition in mesoderm migration. Science 292(5517): 737-740.

Santiago-Martinez, E., Soplop, N.H., and Kramer, S.G. 2006. Lateral Positioning at the midline: Slit and Robos guide Drosophila heart cell migration. Proc Natl Acad Sci USA 103(33): 12441-12446.

Santiago-Martinez, E., Soplop, N., Rajesh Patel and Kramer, S.G. 2008. Repulsion by Slit and Robo prevents Shg/E-Cadherin-mediated cell adhesion during for Drosophila heart tube lumen formation. J. Cell Biol. 182: 241–248.

Guerin, C. M., and Kramer, S.G. 2009. Tumbleweed/RacGAP50C directs perinuclear gamma-tubulin localization to organize the uniform microtubule array required for Drosophila myotube extension. Development 136: 1411-1421.

Guerin, C. M., and Kramer, S.G. 2009. Cytoskeletal Remodeling During Myotube Assembly and Guidance: Coordinating the Actin and Microtubule Networks. Commun Integr Biol 2(5): 452-457.

Soplop, N.H., Patel, R., and Kramer, S.G. 2009. Preparation of late stage embryos for transmission electron microscopy of the Drosophila embryonic heart tube. J Vis Exp, in press.

C. Research Support R01 AR054482 NIH, NIAMS Myotube Guidance in Drosophila Award Period: 03/01/2006 to 02/28/2011 Role: Principal Investigator This project involves studying the specificity of muscle attachment site selection during Drosophila muscle development. Specifically, the aims of this proposal are: 1) to characterize the bi-functional role of the extracellular matrix molecule Slit in muscle guidance, 2) to identify and characterize new molecules required for muscle attachment site selection, 3) to develop live imaging techniques to study in vivo muscle cell migration in wild type and mutant backgrounds. National Science Foundation Award ID# 0744165 Heart tube formation in Drosophila Award Period: 04/01/2008 to 03/30/2011 Role: Principal Investigator This project involves the study of lumen formation during the assembly of the Drosophila heart tube. Specifically experiments are proposed to test the hypothesis that Slit and Robo expression determines the site of lumen formation in heart cells. American Heart Association Scientist Development Grant #0435395T Investigation of Slit function during development of the embryonic heart Award period: 7/1/04 to 6/30/07 (completed) Role: Principal Investigator The primary objective of this proposal is to characterize the role of Slit and Robo receptors during morphogenesis of the Drosophila embryonic heart tube. Experiments are proposed to test the hypothesis that Slit is functioning as a guidance signal to direct heart cell migration and heart tube fusion.





NAME Kukor, Jerome J. eRA COMMONS USER NAME (credential, e.g., agency login)

POSITION TITLE Professor Dean of Academic Programs, SEBS Interim Dean, Graduate School - New Brunswick



College of Steubenville B.A. 1968-1972 Biology University of Michigan M.S. 1972-1975 Biology University of Michigan Ph.D. 1975-1979 Microbiology University of Michigan Post-doc 1979-1982 Enviro. Microbiology

A. Positions and Honors. Positions and Employment 1982-1985 Assistant Research Scientist, Division of Biological Sciences, University of Michigan 1985-1986 Senior Research Fellow, Dept of Microbiology & Immunol., Univ. of Michigan Medical School 1986-1992 Asst. Research Scientist, Dept. of Microbiology & Immunol., Univ. of Michigan Med. School 1992-1993 Assoc. Research Scientist, Dept. of Microbiology & Immunol., Univ. of Michigan Med. School 1993-1996 Assoc. Res. Sci. & Lecturer, Dept. of Microbiology & Immunol., Univ. of Michigan Med. Schl. 1996-1997 Senior Assoc. Res. Sci. & Lect., Dept. of Microbiology & Immunol., U. of Mich. Med. School 1997-2002 Asst Prof, Dept. of Enviro Sci & Biotech Center for Ag & the Environment, Rutgers University 2002-2008 Assoc Prof, Dept. of Enviro Sci & Biotech Center for Ag & the Environment, Rutgers University 2008-present Professor, Dept. of Enviro Sci & Biotech Center for Ag & the Environment, Rutgers University 2006-present Dean of Academic Programs, School of Environmental and Biological Sciences, Rutgers

University 2008-present Dean of Academic Programs, School of Environmental and Biological Sciences, and Interim

Dean of the Graduate School – New Brunswick, Rutgers University

Other Experience and Professional Activities 1997, Review Panel Member, USEPA National Health and Environmental Effects Research Laboratory 1997-2004, Member of the Editorial Board, Applied and Environmental Microbiology 2001-2005, Editor, Applied Microbiology and Biotechnology 2000, Review Panel Member, Dept. of Defense/Dept. of Energy/Environmental Protection Agency Strategic

Environmental Research and Development Program. 2001, Review Panel Member, U. S. Department of Energy Microbial Cell Program. 2001, Review Panel Member, U. S. Department of Energy Microbial Genome Program 2004, Review Panel Member, U. S. Department of Energy Microbial Cell Program. 2005, Review Panel Member, U. S. Department of Energy Genomes to Life Program 2006, Review Panel Member, U. S. Department of Energy Genomics:Genomes to Life Program

Honors 1993, Certificate of Merit from Michigan Governor John Engler for a commitment to excellence and provision of

leadership in the Cooperative Bioremediation Research for Michigan project.



2002, Research Excellence Award, Cook College/New Jersey Agricultural Experiment Station B. Selected peer-reviewed publications (limited to 10) 1) Park, J., J. Malinverni, P. Adriaens, and J. J. Kukor. 2003. Quantitative structure-activity relationship

(QSAR) analysis of aromatic effector specificity in the NtrC-like transcriptional activators from aromatic oxidizing bacteria. FEMS Microbiol. Lett. 224:45-52. PMID:12855166.

2) Wawrik, B., L. Kerkhof, G. J. Zylstra, and J. J. Kukor. 2005. Identification of unique type II polyketide synthase genes in soil. Appl. Env. Microbiol. 71:2232-2238. PMID:15870305.

3) Wawrik, B., L. Kerkhof, J. J. Kukor, and G. J. Zylstra. 2005. Effect of carbon source enrichment on bacterial diversity recovered from soil. Appl. Environ. Microbiol. 71:6776-6783. PMID:16269709.

4) Ni Chadhain, S. M., R. S. Norman, K. Pesce, J. J. Kukor, and G. J. Zylstra. 2006. Microbial dioxygenase gene population shifts during polycyclic aromatic hydrocarbon biodegradation. Appl. Environ. Microbiol. 72:4078-4087. PMID:16751518.

5) Johnson, D. R., J. Park, J. J. Kukor and L. M. Abriola. 2006. Effect of carbon starvation on toluene degradation activity by toluene monooxygenase-expressing bacteria. Biodegradation 17:437-445.

6) Kim, S.-I., J. J. Kukor, K.-H. Oh and H.-Y. Kahng. 2006. Evaluating the genetic diversity of dioxygenases for initial catabolism of aromatic hydrocarbons in Pseudomonas rhodesiae KK1. Enzyme Microb. Technol. 40:71-78.

7) Moon, H. S., H.-Y. Kahng, J. Y. Kim, J. J. Kukor and K. Nam. 2006. Determination of biodegradation potential by two culture-independent methods in PAH-contaminated soils. Environ. Pollut. 140:536-545. PMID:16490294.

8) Wawrik, B., D. Kutliev, U. A. Abdivasievna, J. J. Kukor, G. J. Zylstra, and L. J. Kerkhof. 2007. Biogeography of actinomycete communities and Type II polyketide synthase genes in soils collected in New Jersey and Central Asia. Appl. Environ. Microbiol. 73:2982-2989. PMID: 17337547.

9) Lee, D. -H., D. -C. Oh, Y. -S. Oh, J. C. Malinverni, J. J. Kukor and H. -Y. Kahng. 2007. Cloning and characterization of monofunctional catalase from photosynthetic bacterium Rhodospirillum rubrum S1. J. Microbiol. Biotechnol. 17:1460-1468.

10) Wawrik, B., D. Kutliev, U. A. Abdivasievna, J. J. Kukor, G. J. Zylstra and L. Kerkhof. 2007. Biogeography of actinomycete communities and type II polyketide synthase genes in soils collected in New Jersey and Central Asia. Appl. Environ. Microbiol. 73:2982-2989.

C. Research Support. Ongoing Research Support P42 ES004911 Kaminsky (PI) 4/06-3/11 NIEHS Environmental, Microbial, and Mammalian Biomolecular Responses to AhR Ligands The major goal of this project is to develop molecular tools for tracking genes for PAH, PCB, and dioxin

degradation in soil Role: Co-investigator of Project 6 "Molecular Insight into Polyaromatic Toxicant Degradation by Microbial

Communities” Completed Research Support U01 TW006674 Raskin (PI) 09/01/03-08/31/09 National Institutes of Health International Cooperative Biodiversity Group: Building New Pharmaceutical Capabilities in Central Asia



The major goal of this project is to bioprospect for new microorganisms from soils and sediments in Central Asia, and to screen for antimicrobial lead compounds.

Role: Co-Investigator 5 P42 ES04911-17 Kaminski (PI) 04/01/00 - 03/31/06 NIH/NIEHS Health Hazards From Groundwater Contamination (Program Project) Processes Influencing the Natural Attenuation of Organic Contaminant Plumes (Subproject 5) The major goal of this project is to investigate microbial processes important in natural attenuation of fuel hydrocarbons, chlorinated solvents, and related groundwater contaminants. Role: Co-Investigator R21 ES012824 Zylstra (PI) 09/30/03 - 08/31/05 Nat. Inst. of Enviro. Health Sciences Molecular Assessment of Hydrocarbon Degradation The major goal of this project is to develop molecular tools to assess microbial population changes during remediation applications. Role: Co-Investigator 01HQGR0093 Kukor (PI) 05/01/03-04/30/06 U. S. Geological Survey (Water Resources Research Institute) Investigation of Design Parameters for Engineered Rhizoremediation Systems to Treat Contaminated Sediments In Situ The major goal of this project is to investigate key design features of a model engineered rhizoremediation system to treat sediments contaminated with complex mixtures of anthropogenic organic pollutants. Role: PI 247601 Kukor (PI) 07/01/01-06/30/06 New Jersey Agricultural Experiment Station, Program Enhancement Grants Microbial Bioprospecting in Support of New Jersey Agriculture and Industry” The major goal is to develop a self-sustaining university-industrial partnership for bioprospecting for novel microbial isolates, genes, enzymes, and transformation pathways. DE-FG02-02ER63401 Kukor (PI) 06/01/02-05/31/03 U. S. Department of Energy Joint United States-European Union Theoretical and Practical Course on Environmental Biotechnology” Goal: this grant supported a biotechnology short course to be held in Madrid, Spain. Role: PI

6PHS 398/2590 (Rev. 05/01) Page Biographical Sketch Format Page 6

Principal Investigator/Program Director (Last, First, Middle): Lattime, Edmund C.



NAME

LATTIME, Edmund C. eRA COMMONS USER NAME

lattime

POSITION TITLE

Professor of Surgery, Molecular Genetics, Microbiology & Immunology



Gettysburg College, Gettysburg, PA B.A. 1973 BIOLOGY Rutgers University, Newark, NJ PH.D. 1977 IMMUNOLOGY Sloan-Kettering Institute, New York, NY POST DOC 1977-79 IMMUNOLOGY


1979-1984 Research Associate, Cellular Immunology, Sloan-Kettering Institute for Cancer

Research, New York, NY 1985-1989 Assistant Laboratory Member, Immunology Program, Sloan-Kettering Institute for

Cancer Research, New York, NY 1989 Associate Laboratory Member, Immunology Program, Sloan-Kettering Institute for

Cancer Research, New York, NY 1989-1995 Associate Professor, Department of Medicine, Division of Neoplastic Diseases,

Thomas Jefferson Medical College, Philadelphia, PA 1990-1995 Associate Professor, Department of Microbiology and Immunology, Thomas Jefferson

University, Philadelphia, PA 1991-1998 Member, Jefferson Cancer Institute, Thomas Jefferson University, Philadelphia, PA 1995-1998 Professor, Department of Medicine, Division of Neoplastic Diseases, Thomas

Jefferson Medical College, Philadelphia, PA 1995-1998 Professor, Department of Microbiology and Immunology, Thomas Jefferson University,

Philadelphia, PA 1998-present Professor (with tenure), Department of Surgery, University of Medicine and Dentistry

of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ 1998–present Director, Surgical Oncology Research, Department of Surgery, University of Medicine

and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ

1998 – present Professor, Department of Molecular Genetics, Microbiology & Immunology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ

1998-present Associate Director for Education and Training Programs, The Cancer Institute of New Jersey, New Brunswick, NJ

2008–present Deputy Director, The Cancer Institute of New Jersey, New Brunswick, NJ

Principal Investigator/Program Director (Last, First, Middle): Lattime, Edmund C. Honors and Awards: 1979-1982 Young Investigator Award, National Cancer Institute 1984-1989 Scholar Award, Leukemia Society of America

Advisory Committees: 1995 - 1999 Member, USPHS/NCI Experimental Therapeutics II (ET2) Study Section 1995 - 1999 Member, Am. Cancer Soc. Immunology and Immunotherapy Study Section 1999 – 2003 Member and Chair, NIH SBIR Study Section in Oncology 2003 – 2005 Member, NCI/BRB Oversight Committee 2003 – 2006 Ad hoc, USPHS/NCI Cancer Immunopathology and Immunotherapy (CII) Study

Section 2006 Ad hoc, NCI Subcommittee F Manpower and Training Study Section 2006 – 2008 Chair, USPHS/NCI Cancer Immunopathology and Immunotherapy (CII) Study Section 2007 Chair, NIH Roadmap Interdisciplinary Research Consortium (U54) Review Special

Emphasis Panel 2008 – present Ad hoc site visit team, NCI, Centers Branch 2009 Chair, NIH-NCRR Panel for mouse biorepositories 2009 Chair, NIH-NCRR COBRE Review Panel 2009 Senior Editor, NCI Challenge Grants

B. Selected peer-reviewed publications (in chronological order).

(Publications selected from >100 publications)

1. Lattime, E.C., Stoppacciaro, A., Khan, A., and Stutman, O. 1988. Human natural cytotoxic activity mediated by tumor necrosis factor: Regulation by interleukin-2. J. Natl. Cancer Inst. 80:1035-1038.

2. Lattime, E.C., Stoppacciaro, A., and Stutman, O. 1988. Limiting dilution analysis of tumor necrosis factor (TNF) producing cells in C3H/HeJ mice. J. Immunol. 141:3422-3428.

3. Lattime, E.C. and Stutman, O. 1989. Tumor growth in-vivo selects for resistance to tumor necrosis factor (TNF). J. Immunol. 143:4317-4323.

4. Lattime, E.C. and Stutman, O. 1991. Thymic lymphomas mediate non-MHC restricted, TNF dependent lysis of the murine sarcoma WEHI-164. Cell. Immunol. 136:69-79.

5. Lattime, E.C. and Stutman, O. 1992. WEHI-164 clone 2F: In-vitro and in-vivo anti-tumor effects of tumor necrosis factor (TNF) and gamma interferon. Nat. Immunity and Cell Growth Reg. 11:34-45.

6. Lattime, E.C., Gomella, L.G., and McCue, P.A. 1992. Murine bladder carcinoma cells present antigen to BCG-specific CD4+ T cells. Cancer Res. 52:4286-4290

7. Kalman, B., Lublin, F.D., Lattime, E.C., Joseph, J., and Knobler, R.L. 1993. Effects of staphylococcal enterotoxin B on T cell receptor V utilization and clinical manifestations of experimental allergic encephalomyelitis. J. Neuroimmunol. 45:83-88.

8. Alexander, A.A., Liu, J.B., McCue, P., Gomella, L.G., Ross, R.P., and Lattime, E.C. 1993. Intravesical growth of murine bladder tumors assessed by transrectal ultrasound J. Urol. 150:525-528.

9. Gomella, L.G., McGinnis, D.E., Lattime, E.C., Butler, K., Baltish, M., Thompson, I., and Marshall, M.E. 1993. Treatment of transitional cell carcinoma of the bladder with intravesical interleukin-2: A pilot study. Cancer Biotherapy 8:223-227.




10. Lee, S.S., Eisenlohr, L.C., McCue, P.A., Mastrangelo, M.J., and Lattime, E.C. 1994. Intravesical gene therapy: In-vivo gene transfer using recombinant vaccinia virus vectors. Cancer Res. 54:3325-3328.

11. McAveney, K.M., Gomella, L.G., and Lattime, E.C. 1994. Induction of TH1 and TH2 associated cytokine mRNA in mouse bladder following intravesical growth of the murine bladder tumor MB49 and BCG immunotherapy. Cancer Immunol. Immunother. 39:401-406.

12. Mastrangelo, M.J., Maguire, H.C., McCue, P., Lee, S.S., Alexander,A., Nazarian, L.N., Eisenlohr, L.C., Nathan, F.E., Berd, D., and Lattime, E.C. 1995. A pilot study demonstrating the feasibility of using intratumoral vaccinia injections as a vector for gene transfer. Vaccine Res.4: 55-69.

13. Lattime, E.C., Mastrangelo, M.J., Bagasra, O., Li, W., and Berd, D. 1995. Expression of cytokine mRNA in human melanoma tissues. Cancer Immunol. Immunother. 41:151-156.

14. Santra, M., Skorski, T., Calabretta, B., Lattime, E.C., and Iozzo, R.V. 1995. De novo decorin gene expression suppresses the malignant phenotype in human colon cancer cells. Proc. Natl. Acad. Sci. USA 92:7016-7020.

15. McCue, P.A., Gomella, L.G., Veltri, R.W., Marley, H.M., Miller, M.C., and Lattime, E.C. 1996. Development of secondary structure, growth characteristics, and cytogenetic analysis of human transitional cell carcinoma xenografts in scid/scid mice. J. Urol. 155:1128-1132.

16. Berd, D., Mastrangelo, M.J., Lattime, E., Sato, T., and Maguire, H.C. Jr. 1996. Melanoma and vitiligo: immunology’s Grecian urn. Cancer Immunol. Immunother. 42:263-267.

17. Sato, T., McCue, P., Masuoka, K., Salwen, S., Lattime, E.C., Mastrangelo, M.J., and Berd, D. 1996. Interleukin-10 production by human melanoma. Clin. Cancer Res. 2:1383-1390.

18. Maguire, H.C. Jr., Ketcha, K.A. and Lattime, E.C. 1997. Neutralizing anti-IL10 antibody upregulates the induction and elicitation of contact hypersensitivity J. Interferon and Cytokine Res. 17:763-768.

19. Maguire, H.C. Jr., Berd, D., Lattime, E.C., McCue, P.A., Kim, S., Chapman, P.B., and Mastrangelo, M.J. 1998. Phase I study of R24 in patients with metastatic melanoma including evaluation of Immunologic Parameters Cancer Biotherapy & Radiopharmaceuticals 13:13-23.

20. Halak, B.K., Maguire, H.C. Jr. and Lattime, E.C. 1999. Tumor-associated IL10 inhibits type 1 immune responses directed towards a tumor antigen and non tumor antigen present at the tumor site Cancer Res. 59:911-917.

21. Mastrangelo, M.J., Maguire, H.C. Jr., Eisenlohr, L.C., Laughlin, C.E., Monken, C.E., McCue, P.A., Kovatich, A.J., and Lattime, E.C. 1999. Intratumoral recombinant GM-CSF encoding virus as gene therapy in patients with cutaneous melanoma. Cancer Gene Therapy 5:409-422.

22. Gomella, L.G., Mastrangelo, M.J., McCue, P.A., Maguire, H.C. Jr., Mulholland, S.G., and Lattime, E.C. 2001. Phase I study of intravesical vaccinia virus as a vector for gene therapy of bladder cancer. J. Urology 166:1291-1295.

23. Mastrangelo, M.J. and Lattime, E.C. 2002. Virotherapy clinical trials for regional disease: In situ immune modulation using recombinant poxvirus vectors Cancer Gene Therapy 9:1013-1021.

24. Yang, A.S. and Lattime, E.C. 2003. Tumor-induced IL-10 Suppresses the Ability of Splenic Dendritic Cells to Stimulate CD4 and CD8 T Cell Responses. Cancer Res. 63:2150-2157.

25. Yang, A.S. and Monken, C.E., and Lattime, E.C. 2003. Intratumoral vaccination with vaccinia expressed tumor antigen and GM-CSF overcomes immunological ignorance to tumor antigen. Cancer Res. 63:6956-6961.

26. Strair, R.K., Schaar, D., Medina, D., Todd, M.B., Aisner, J., DiPaola, R.S., Manago, J., Knox, B., Jenkinson, A., Senzon, R., Baker, C., Dudek, L., Ciardella, M., Kuriyan, M., Rubin, A. and Lattime, E.C. 2003. Anti-neoplastic effects of partially HLA-matched irradiated blood mononuclear cells in patients with renal cell carcinoma, J. Clin., Oncol. 21:3785-3791.



27. DiPaola, R., Plante, M., Kaufman, H., Petrylak, D., Israeli, R., Lattime, E., Manson, K., Schuetz, T. 2006, A Phase I trial of pox PSA vaccines (PROSTVAC(R)-VF) with B7-1, ICAM-1, and LFA-3 co-stimulatory molecules (TRICOMtrade mark) in patients with prostate cancer, J. Transl. Med. 4:1-5.

28. Zhang, Z., Monken, C.E., Zhang, Y., Lenard, J., Mizushima, N., Lattime, E.C., Jin, S., 2006. Cellular autophagy machinery is not required for vaccinia virus replication and maturation, Autophagy 2:91-95.

29. Gabriel EM, Lattime EC., 2007, Anti-CTL-associated antigen 4: are regulatory T cells a target?, Clin Cancer Res. 13:785-788.

30. DiPaola, RS and Lattime, EC, 2007, Bacillus Calmette-Guerin Mechanism of Action: The role of immunity, apoptosis, necrosis, and autophagy, J. Urol. (Epub ahead of print).

C. Research Support Active 2R01CA042908-21 (Lattime) 1/1/08 – 12/31/12 4.1 calendar NIH/NCI $199,455 In-Situ activation of antitumor effectors The major goals of this ongoing project are to study the tumor-host immune interaction in murine models of breast and bladder cancer. The studies focus on identifying tumor-associated immune escape mechanisms and developing genetically-based vaccine and localized treatment strategies for overcoming escape. R21-CA121589 (Lattime) 8/1/06 – 6/30/10 1.2 calendar NIH/NCI $155,117 Intravesical rF-GMCSF and rF-TRICOM in the treatment of advanced bladder cancer This award funds the clinical and laboratory correlative studies of our NCI (CTEP) sponsored Phase I trial of intravesical recombinant poxvirus constructs given neoadjuvantly to patients with advanced bladder cancer scheduled for cystectomy. U01-CA07031 (DiPaola) 5/1/08 – 2/28/13 0.6 calendar NIH/NCI $164,744 Early Clinical Trials of New Anti-Cancer Agents with Phase I Emphasis Grant E. Lattime, Co-PI P30-CA72720 (DiPaola) 2.4 calendar NIH/NCI Cancer Center Support Grant E. Lattime, Deputy Director, Program Leader, Shared Resource Director W81XWH-09-1-0145 04/01/09-03/31/14 0.6 calendar Department of Defense (DiPaola) $1,560,000 Prostate Clinical Trials Consortium Grant E. Lattime, Investigator The major goals include the development of investigator initiated clinical trials that are conducted across multiple University Cancer Centers. 09-1973-CCR-EO (Reiss) 6/26/09 - 6/25/10 0.6 calendar New Jersey Commission on Cancer Research imaging and Targeting TGF-β in Metastatic Breast Cancer E. Lattime, Co-Investigator



The aims of this project are: (1) Develop sophisticated imageable models for each of these major clinical BC subtypes (TN, HER2+, ER+ and their resistant counterparts) (Kang); (2) Determine whether or not metastasis is dependent on tumor cell intrinsic TGFβ signaling in each of these settings using genetic ablation of Smad4 (Kang); (3) Determine whether or not metastasis is dependent on tumor associated active TGFβ in each of these settings by treatment with the TGFβ neutralizing antibody, 1D11. HHS Contract No. (Lattime) 8/1/08 – 7/31/10 .6 calendar PIID No. HHSN261200544005C $702,886 NCI Control No. N01-PC-54405 NIH/NCI Surveillance, Epidemiology and End Results (SEER) The Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute (NCI) is an authoritative source of information on cancer incidence and survival in the United States. SEER currently collects and publishes cancer incidence and survival data from population-based cancer registries covering approximately 26 percent of the US population. Pending Validation of PROMIS in Diverse Cancer Populations (Potosky) NIH/NCI 3/1/10-9/29/13 .24 calendar Lattime, Subcontract PI $ 83,009 The goal of the study is to evaluate the usefulness of a patient reported outcomes measurement information system (PROMIS) item banks in diverse cancer patient populations and in clinical settings. SEER subcontract, Dr. Lattime is the acting Director of the NJ SEER Program in his role as Deputy Director CINJ. A Genome-Wide Admixture Scan of Multiple Myeloma in African-Americans (Cozen) NIH/NCI 4/1/10-3/31/13 .24 calendar Lattime, Subcontract PI $ 62,481 The goal of this proposal is to identify the genetic component underlying the large racial/ethnic health disparity of multiple myeloma (MM). For maximum success, a comprehensive study of genetic variation must be performed within the population most at risk. The study will conduct a well-powered GWAS of MM in the African American population followed by generalizability/replication testing of the most significant associations in MM cases and controls of White European ancestry to evaluate their contribution to racial/ethnic disparities. SEER subcontract, Dr. Lattime is the acting Director of the NJ SEER Program in his role as Deputy Director CINJ. Epidemiologic Study of Hepatocellular Carcinoma in the US (Yu) NIH/NCI 7/1/10-12/31/14 .24 calendar Lattime, Subcontract PI $ 86,597 SEER subcontract, Dr. Lattime is the acting Director of the NJ SEER Program in his role as Deputy Director CINJ. Comparative Effectiveness of Treatments for Localized Prostate Cancer .24 calendar NIH/NCI 8/1/10-7/31/13 $159,925 Lattime, Subcontract PI SEER subcontract,

Completed Research Support

2 R01 CA55322-05 (P.I. E.C. Lattime) 5/5/93 to 4/30/04 NIH - National Cancer Institute Human antitumor effector mechanisms The major goals of this project were to study the tumor-host immune interaction in patients with bladder cancer. These studies have resulted in developing a novel localized treatment strategy utilizing vaccinia recombinants and testing same in patients with melanoma and bladder cancer.



NAME Leroy F. Liu eRA COMMONS USER NAME LIU2004

POSITION TITLE Professor of Pharmacology



National Taiwan University, Taiwan B. S. 1967-1971 Chemistry University of California, Berkeley, CA Ph. D. 1973-1977 Biochemistry Harvard University, Cambridge, MA Postdoct. 1978-1979 Molecular Biology University of San Francisco, San Francisco, CA. Postdoct. 1979-1980 Molecular Biology

A. Positions and Honors. Positions: Assistant Professor (April 1980 - May, 1984), Department of Biological Chemistry, Johns Hopkins School of Medicine. Associate Professor (May 1984 - Oct. 1988), Department of Biological Chemistry, Johns Hopkins School of Medicine. Professor (November 1, 1988 - 1992), Department of Biological Chemistry, Johns Hopkins School of Medicine. Professor and Chairman (Oct. 1992-present), Department of Pharmacology, University of Medicine and Dentistry of New Jersey (UMDNJ)-Robert Wood Johnson Med. Sch. (Oct. 1992-present). Program Leader, The Cancer Pharmacology Program, the Cancer Institute of New Jersey (CINJ). Honors/services: C. Chester Stock Award, Memorial Sloan-Kettering Cancer Center, 2003; Bruce F. Cains Memorial Award, AACR, 1997; George H. Hitchings Award, Burroughs Wellcome Fund, 1989; Searle Scholar, 1981-1984. Member of NSF Biochemistry Study Section, 1985-1989; Member of NIH Molecular Biology Study Section, 1991-1996. Adv. in Pharmacology, 1994; Associate Editor, Cancer Research, 1989-2000; Assoc. Editor, Anticancer Res. 1997-present; Assoc. Editor, J. Biol. Chem. editorial board, 1998-present. Honorary Professor of Hong Kong Baptist University, 2005-2008. Academician of Academia Sinica (Taiwan), 2000-present. Scientific Advisory Board member of various research institutes. B. Selected peer-reviewed publications (since 2003).

1. Makhey, D., Li, D., Zhao, B., Sim, S.-P., Li, T. K., Liu, A., Liu, L. F. and LaVoie, E. J. “Substituted Benzo[i]phenanthridines as Mammalian Topoisomerase-Targeting Agents” Bioorganic Med. Chem., 11:1809-1820 ( 2003)

2. Ruchelman, A. L., Singh, S. K., Ray, A., Wu, X. H., Yang, J.-M., Li, T. K., Liu, A., Liu, L. F., and LaVoie, E. J. “5H-Dibenzo[c,h]1,6-naphthyridin-6-ones: Novel Topoisomerase I-Targeting Anticancer Agents with Potent Cytotoxic Activity” Bioorganic Med. Chem., 11:2061-2073 (2003).

3. Yu, Y., Singh, S. K., Liu, A., Li, T.-K., Liu, L. F., and LaVoie, E. J. “Substituted Dibenzo[c,h]cinnolines: Topoisomerase I-Targeting Anticancer Agents” Bioorganic Med. Chem., 11:1475-1491 (2003).

4. Li, D., Zhao, B., Sim S.-P., Tsai-Kun Li, T.-K., Liu, A., Liu, L. F., and LaVoie, E. J. “2,3-Dimethoxybenzo[i]phenanthridines: Topoisomerase I-Targeting Anticancer Agents” Bioorganic Med. Chem.;11:521-528 (2003).

5. Nur-E-Kamal, A., Li, T.-K., Zhang, A, Qi, H., Hars, E. and Liu, L. F. “Single-stranded DNA induces ATM/p53-dependent DNA damage and apoptotic signals” J. Biol. Chem. 278:12475-12481 (2003).

6. Desai, S. D., Zhang, H., Rodriguez-Bauman, A., Yang, J.-M., Wu, X., Gounder, M. K., Rubin, E. H. and Liu, L. F. “Transcription-Dependent Degradation of Topoisomerase I-DNA Covalent Complexes” Mol. Cell. Biol. 23:2341-2350 (2003).

7. Xiao, H., Mao, Y., Desai, S. D., Zhou, N., Ting, C.-Y., Hwang, J. and Liu, L. F. “The Topoisomerase IIβ Circular Clamp Arrests Transcription and Signals a 26S Proteasome Pathway” Proc. Natl. Acad. Sci. USA. 100:3239-3244 (2003).

8. Xiao, H., Li, T.-K., J.-M. Yang and Liu, L. F. “Acidic pH Induces Topoisomerase II-Mediated DNA Damage” Proc. Natl. Acad. Sci. USA. 100: 5205-5210 (2003).

9. Liu, L. F. “Degradation of Topoisomerase Cleavable Complexes” in DNA Topoisomerases in Cancer Therapy: Present and Future, Ed. Toshiwo Andoh, Kluwer Academic/Plenum Publishers, London UK. pp79-88 (2003).

10. Qi, H., Li, T.-K., Kuo, D., Nur-E-Kamal, A. and Liu, L. F. “Inactivation of Cdc13p triggers MEC1-dependent apoptotic signals in yeast” J. Biol. Chem. 278:15136-15141 (2003).

11. Zhou, N., Xiao, H., Nur-E-Kamal, A. and Liu, L. F. “DNA damage-mediated apoptosis induced by selenium compounds” J. Biol. Chem. 278:29532-29537 (2003).

12. Singh, S. K., Ruchelman, A. L., Li, T. K., Liu, A., Liu, L. F., and LaVoie, E. J. “Nitro and amino substitution in the D-ring of 5-(2-dimethylaminoethyl)- 2,3-methylenedioxy-5H-dibenzo[c,h][1,6]naphthyridin-6-ones: effect on topoisomerase-I targeting activity and cytotoxicity”. J. Med. Chem. 46:2254-2257 (2003).

13. Li, D., Zhao, B., Sim, S. P., Li, T. K., Liu, A., Liu, L. F., and LaVoie, E. J. “8,9 -methylenedioxybenzo[i]phenanthridines: topoisomerase I-targeting activity and cytotoxicity”. Bioorg. Med. Chem. 11:3795-3805 (2003).

14. Li, T.-K., Desai, S. D., Daroui, P., Liu, A. A., Eszter S. Hars, Ruchelman, A. L., LaVoie, E. J. and Liu, L. F. “Characterization of ARC-111 as a Novel Topoisomerase I-Targeting Anticancer Drug” Cancer Res. 63:8400-8407 (2003).

15. Kerrigan J. E., Pilch, D.S., Ruchelman, A.L., Zhou, N, Liu, A., Liu, L., and LaVoie, E. J. “5H-8,9-Dimethoxy-5-(2-N,N-dimethylaminoethyl)dibenzo[c,h]naphthyridin-6-ones and related compounds as TOP1-Targeting agents: influence of structure on the ternary cleavable complex formation”. Bioorg. Med. Chem. Lett. 13:3395-3399 (2003).

16. Ting, C. Y., Hsu, C. T., Hsu, H. T., Su, J. S, Chen, T. Y., Tarn, W. Y., Kuo, Y. H., Whang-Peng, J., Liu, L. F., and Hwang, J. “Isodiospyrin as a novel human DNA topoisomerase I inhibitor”. Biochem. Pharmacol. 66:1981-1991 (2003).

17. Daroui, P., Desai, S. D., Li, T.-K., Liu, A. and Liu, L. F., “Hydrogen peroxide induces topoisomerase Ι-mediated DNA damage and cell death”. J. Biol. Chem. 279:14587-14594 (2004).

18. Ruchelman, A. L., Singh, S. K., Ray, A., Wu, X., Yang, J. M., Zhou, N., Liu, A., and Liu, L. F., LaVoie, E. J. “11H-Isoquino[4,3-c]cinnolin-12-ones; novel anticancer agents with potent topoisomerase I-targeting activity and cytotoxicity”. Bioorg Med Chem. 12:795-806 (2004).

19. Ruchelman, A. L., Kerrigan, J. E., Li, T. K., Zhou, N., Liu, A., Liu, L. F., and LaVoie, E. J. Nitro and amino substitution within the A-ring of 5H-8,9-dimethoxy-5-(2-N,N-dimethylaminoethyl)dibenzo[c,h][1,6]naphthyridin-6-ones: influence on topoisomerase I-targeting activity and cytotoxicity. Bioorg Med Chem. 12:3731-3742 (2004).

20. Nur-E-Kamal, A., Gross, S. R., Pan, Z., Balklava, Z., Ma, J., Liu, L. F. Nuclear translocation of cytochrome c during apoptosis. J. Biol. Chem. 279:24911-24914 (2004).

21. Rajendra, R., Malegaonkar, D., Pungaliya, P., Marshall, H., Rasheed, Z., Brownell, J., and Liu, L. F., Lutzker, S., Saleem, A., and Rubin E. H. Topors functions as an E3 ubiquitin ligase with specific E2 enzymes and ubiquitinates p53. J. Biol. Chem. 279:36440-36444 (2004).

22. Ruchelman, A. L., Houghton, P. J., Zhou, N., Liu, A., Liu, L. F., and LaVoie, E. J. “5-(2-aminoethyl)dibenzo[c,h]napthyridin-6-ones:variation of N-alkyl substituents modulates sensitivity to efflux transporters associated with multidrug resistance” J. Med. Chem. 48:792-804 (2005).

23. Zhu, S., Ruchelman, A. L., Zhou, N., Liu, A. A., Liu, L. F., and Lavoie, E. J. Esters and amides of 2,3-dimethoxy-8,9-methylenedioxy-benzo[i]phenanthridine-12-carboxylic acid: Potent cytotoxic and topoisomerase I-targeting agents. Bioorg Med Chem. 13:8782-6794 (2005).

24. Bacherikov, V. A., Chou, T. C. Dong, H. J., Zhang, X., Chen, C-H., Lin, Y.-W., Tsai, T.-J., Lee, R.-Z., Liu, L. F., and Su, T.-L., Potent antitumor 9-anilinoacridines bearing an alkylating N-mustard residue on the anilino ring: synthesis and biological activity Bioorganic & Medicinal Chemistry 13:3993-4006 (2005)

25. Zhu, S., Ruchelman, A. L., Zhou, N., Liu, A. A., Liu, L. F., and Lavoie, E. J.6-Substituted 6H-dibenzo[c,h][2,6]naphthyridin-5-ones: Reversed lactam analogues of ARC-111 with potent topoisomerase I-targeting activity and cytotoxicity. Bioorg Med Chem. 14:3131-43 (2006).

26. Su, T. L., Lin, Y. W., Chou, T. C., Zhang, X. Bacherikov, V. A., Chen, C. H., Liu, L. F. and Tsai, T. J. Potent antitumor 9-anilinoacridines and acridines bearing an alkylating N-mustard residue on the acridine chromophore: synthesis and biological activity. J. Med. Chem. 49:3710-8 (2006).

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16759114&query_hl=1&itool=pubmed_docsum

27. Desai, S. D., Haas, A. L., Wood, L. M., Tsai, Y-C., Pestka, S., Rubin, E. H., Saleem, A., Nur-E-Kamal A. and Liu, L. F. “Elevated expression of ISG15 in tumor cells interferes with the ubiquitin/26S proteasome pathway” Cancer Res. 66:921-928 (2006).

28. Yang, M., Hsu, C-J., Ding, J.-Y., Liu, L. F. and Hwang, J. “Assembly of a polymeric chain of SUMO-1 on human topoisomerase I in vitro” J. Biol. Chem. 281:8264-8274 (2006).

29. Hars, E. S., Lyu, Y. L., Lin, C. P. and Liu, L. F. Role of Apoptotic Nuclease Caspase-Activated DNase in Etoposide-Induced Treatment-Related Acute Myelogenous Leukemia. Cancer Res. 66:8975-9 (2006).

30. Zhang, A., Lyu, Y. L., Lin, C. P., Zhou, N., Azarova, A. M., Wood, L. M. and Liu, L. F. A protease pathway for the repair of topoisomerase II-DNA covalent complexes. J. Biol. Chem. 281:35997-36003 (2006).

31. Qi, H. Lin, C.-P., Fu, X., Wood, L. M., A. Liu, A. A., Tsai, Y.-C., Chen, Y., M. Barbieri, C. M., Pilch1, D. S., and Liu, L. F. G-Quadruplexes Induce Apoptosis in Tumor Cells, Cancer Res. 66: 11808-11816 (2006).

32. Lyu, Y. L., Lin, C. P., Azarova, A. M., Cai, L., Wang, J. C. and Liu, L. F. Role of Topoisomerase IIbeta in the Expression of Developmentally Regulated Genes. Mol. Cell. Biol. 26:7929-7941 (2006).

33. Hars, E. S., Qi, H., Ryazanov, A. G., Jin, S., Cai, L., Hu, C. and Liu, L. F. “Autophagy regulates aging in C. elgans”, Autophagy, 3, 93-95 (2007).

34. Tsang, C. K., Qi, H., Liu, L. F. and Zheng, X. F. S. “Targeting Mammalian Target of Rapamycin (mTOR) for Health and Diseases”. Drug Discovery Today, 12:112-124 (2007).

35. Azarova, A. M., Lyu, Y. L., Lin, C.-P., Tsai,Y.-C., Lau, J. Y.-N., Wang, J. C. and Liu, L. F. “Roles of DNA topoisomerase II isozymes in chemotherapy and secondary malignancies” Proc. Natl. Acad. Sci. USA, 104: 11014-11019 (2007).

36. Meiners, S., Ahmed, I., Azarova, A., Lin, C.-P., Lyu, Y.-L., and Liu, L. F. “Role of DNA Topoisomerase IIbeta in Neurite Outgrowth, Brain Res. 1154:50-60 (2007)

37. Lyu, Y. L., Kerrigan, J. E., Lin, C.-P., Azarova, A., Tsai, Y.-C. and Liu, L. F. “Topoisomerase IIβ-Mediated DNA Double-Strand Breaks: Implications in Doxorubicin Cardiotoxicity and Prevention by Dexrazoxane” Cancer Res. 67: 8839-8846 (2007).

38. Zhang, Y., Qi, H., Taylor, R., Xu, W., Liu, L. F. and Jin, S. “The Role of Autophagy in Mitochondria Maintenance: Characterization of Mitochondrial Functions in Autophagy-Deficient S. cerevisiae Strains”. Autophagy. 3: 17404498 (2007).

39. Tsai, Y.-C., Qi, H. and Liu, L. F. “Protection of DNA Ends by Telomeric 3’ G-Tail Sequences” J. Biol. Chem. 282:18786-92 (2007).

40. Fu, X., Wan, S., Lyu, Y. L., Liu, L. F. and Qi, H. “Etoposide Induces ATM-Dependent Mitochondrial Biogenesis through AMPK Activation” PLoS ONE, 3(4): e2009 (2008).

41. Desai, S. D., Wood, L. J., Tsai, Y.-C., Hsieh, T. S., Marks, J. R., Scott, G. L., Giovanella, B. C. and Liu, L. F. “ISG15 as a Novel Tumor Biomarker for Drug Sensitivity” Molecular Cancer Therapeutics, 7 (6):1430-1439 (2008).

42. Satyanarayana, M., Rzuczek, S. G., LaVoie, E. J., Pilch, D. S., Liu, A. Liu, L. F. and Rice, J. E., “Ring-Closing Metathesis for the Synthesis of a Highly G-Quadruplex Selective Macrocyclic Hexaoxazole Having Enhanced Cytotoxic Potency”, Bioorganic and Medicinal Chemistry Letters, 18(13):3802-3804 (2008).

43. Feng, W, Satyanarayana, M, Cheng, L, Liu, A, Tsai, YC, Liu, L. F. and Lavoie, E. J. “Synthesis of N-substituted 5-[2-(N-alkylamino)ethyl]dibenzo[c,h][1,6]naphthyridines as novel topoisomerase I-targeting antitumor agents” Bioorg Med Chem. 16:9295-301. (2008).

44. Lin, C.-P., Ban, Y., Lyu, Y.Lisa, Desai, S. D. and Liu, L. F. “A ubiquitin-proteasome pathway for the repair of Top1-DNA covalent complexes” J. Biol. Chem. 283:21074-21083 (2008).

45. Qi, H, Chen, Y, Fu, X, Lin, C. P., Zheng, X. F. and Liu, L. F. “TOR regulates cell death induced by telomere dysfunction in budding yeast” PLoS ONE. 3(10):e3520. (2008).

46. Feng W, Satyanarayana M, Tsai YC, Liu AA, Liu LF, LaVoie EJ. 12-Substituted 2,3-dimethoxy-8,9-methylenedioxybenzo[i]phenanthridines as novel topoisomerase I-targeting antitumor agents.Bioorg Med Chem. 17:2877-85 (2009).

47. Feng W, Satyanarayana M, Tsai YC, Liu AA, Liu LF, LaVoie EJ. Novel topoisomerase I-targeting antitumor agents synthesized from the N,N,N-trimethylammonium derivative of ARC-111, 5H-2,3-dimethoxy-8,9-methylenedioxy-5-[(2-N,N,N-trimethylammonium)ethyl]dibenzo[c,h][1,6]naphthyridin-6-one iodide. Eur J Med Chem. 44:3433-8 (2009).

48. Sharma L, Tsai YC, Liu AA, Liu LF, LaVoie EJ. Cytotoxicity and TOP1-targeting activity of 8- and 9-amino derivatives of 5-butyl- and 5-(2-N,N-dimethylamino)ethyl-5H-dibenzo[c,h][1,6]naphthyridin-6-ones. Eur J Med Chem. 44:1471-6 (2009).

49. Tsai YC, Qi H, Lin CP, Lin RK, Kerrigan JE, Rzuczek SG, Lavoie EJ, Rice JE, Pilch DS, Lyu YL, Liu LF. A G-quadruplex stabilizer induces M phase cell cycle arrest. J. Biol. Chem. 284:22535-43 (2009).



http://lib.bioinfo.pl/auth:Zhang,Y

http://lib.bioinfo.pl/auth:Qi,H

http://lib.bioinfo.pl/auth:Taylor,R

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http://lib.bioinfo.pl/auth:Liu,L

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http://lib.bioinfo.pl/pmid:17404498

http://lib.bioinfo.pl/pmid:17404498

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50. Lin, C.-P., Ban, Y., Lyu, Y. L. and Liu, L. F. Proteasome-dependent processing of topoisomerase I-DNA adducts into DNA double-strand breaks at arrested replication forks. J. Biol. Chem. 284:28084-92 (2009).

51. Rzuczek SG, Pilch DS, Liu A, Liu L, Lavoie EJ, Rice JEMacrocyclic Pyridyl Polyoxazoles: Selective RNA and DNA G-Quadruplex Ligands as Antitumor Agents. J Med Chem, in press. (2010).

C. Research Support. Ongoing Research Support

RO1CA39662-25 Liu (PI) 7/1/09-6/30/14 NIH/NCI Title: “Mechanism of Antitumor Drugs” The goal of this project is to determine mechanism of action of Top1-tatrgeting drugs. More specifically, the role of ISG15 in camptothecin cytotoxicity will be determined. Role: P.I. RO1CA102463-06 Liu (PI) 7/1/08 - 6/30/13 NIH/NCI Title “Mechanism of action of TOP2-directed anticancer drugs”. The goal of this project is to understand the mechanism of action of TOP2-directed anticancer drugs. Specifically, this project investigates the mechanism of TOP2 isozymes in etoposide-induced t-AML. Role: P. I. T32CA108455-05 Liu (PI) 09/01/2005-08/31/2010 NIH/NCI Training in Cancer Pharmacology The goal of this project is to train predoctoral and postodoctoral fellows in the area of cancer pharmacology. Role: P. I. Institutional Award Liu (PI) 4/1/2008-3/31/2009 RWJMS/CINJ Developing Novel Anticancer Agents against Prostate Cancer. The major goal of this project is to explore new molecular targets and/or pathways for developing novel anticancer drugs. Role: P. I. Pending none

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http://www.ncbi.nlm.nih.gov/pubmed?term=%22Lavoie%20EJ%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/pubmed?term=%22Rice%20JE%22%5BAuthor%5D

Principal Investigator/Program Director (Last, First, Middle): Lobel, Peter



NAME

Lobel, Peter eRA COMMONS USER NAME

LOBEL2003

POSITION TITLE

Professor of Pharmacology, RWJMS Resident Member, CABM



State University of New York at Purchase BA. (Honors) 1978 Biology Columbia University Ph.D. 1985 Biochemistry Washington University School of Med (St. Louis) Postdoc 1988 Molecular Biology

A. Positions and Honors. Positions 1989-present Resident Faculty Member, Center for Advanced Biotechnology and Medicine 1989-present Assistant, Associate, and Professor of Pharmacology, UMDNJ-Robert Wood Johnson Medical

School (RWJMS) 1994-present Member, Cancer Institute of New Jersey Other Experience and Professional Memberships 1999--present Executive Director, CABM/RWJMS/Rutgers Biological Mass Spectrometry Resource/Facility 1991-present NIH study sections and site visits, ad hoc member 2008-present Chairman, RWJMS Biomedical Advisory Committee Honors 1989 Searle Scholar 2007 Excellence in Research Award, UMDNJ Foundation 2007 Visiting Faculty, Mayo Clinic

B. Selected peer-reviewed original research publications (in chronological order). 9. Chen, H. J., Remmler, J., Delaney, J. C., Messner, D. J., and Lobel, P. (1993) Mutational analysis of the cation-independent mannose 6-phosphate/insulin-like growth factor II receptor. A consensus casein kinase II site followed by 2 leucines near the carboxyl terminus is important for intracellular targeting of lysosomal enzymes. J Biol Chem 268, 22338-22346. 11. Valenzano, K. J., Kallay, L. M., and Lobel, P. (1993) An assay to detect glycoproteins that contain mannose 6-phosphate. Anal Biochem 209, 156-162. 12. Bhavsar, J. H., Remmler, J., and Lobel, P. (1994) A method to increase efficiency and minimize anomalous electrophoretic transfer in protein blotting. Anal Biochem 221, 234-242. 15. Sleat, D. E., Chen, T. L., Raska, K., Jr., and Lobel, P. (1995) Increased levels of glycoproteins containing mannose 6-phosphate in human breast carcinomas. Cancer Res 55, 3424-3430. 16. Valenzano, K. J., Remmler, J., and Lobel, P. (1995) Soluble insulin-like growth factor II/mannose 6-phosphate receptor carries multiple high molecular weight forms of insulin-like growth factor II in fetal bovine serum. J Biol Chem 270, 16441-16448. 18. Sleat, D. E., Sohar, I., Lackland, H., Majercak, J., and Lobel, P. (1996) Rat brain contains high levels of mannose-6-phosphorylated glycoproteins including lysosomal enzymes and palmitoyl-protein thioesterase, an enzyme implicated in infantile neuronal lipofuscinosis. J Biol Chem 271, 19191-19198. 19. Chen, H. J., Yuan, J., and Lobel, P. (1997) Systematic mutational analysis of the cation-independent mannose 6-phosphate/insulin-like growth factor II receptor cytoplasmic domain. An acidic cluster containing a key aspartate is important for function in lysosomal enzyme sorting. J Biol Chem 272, 7003-7012.



20. Sleat, D. E., Donnelly, R. J., Lackland, H., Liu, C. G., Sohar, I., Pullarkat, R. K., and Lobel, P. (1997) Association of mutations in a lysosomal protein with classical late-infantile neuronal ceroid lipofuscinosis. Science 277, 1802-1805. 21. Sleat, D. E., Kraus, S. R., Sohar, I., Lackland, H., and Lobel, P. (1997) alpha-Glucosidase and N-acetylglucosamine-6-sulphatase are the major mannose-6-phosphate glycoproteins in human urine. Biochem J 324, 33-39. 22. Sleat, D. E., and Lobel, P. (1997) Ligand binding specificities of the two mannose 6-phosphate receptors. J Biol Chem 272, 731-738. 23. Valenzano, K. J., Heath-Monnig, E., Tollefsen, S. E., Lake, M., and Lobel, P. (1997) Biophysical and biological properties of naturally occurring high molecular weight insulin-like growth factor II variants. J Biol Chem 272, 4804-4813. 27. Sohar, I., Sleat, D., Gong Liu, C., Ludwig, T., and Lobel, P. (1998) Mouse mutants lacking the cation-independent mannose 6-phosphate/insulin-like growth factor II receptor are impaired in lysosomal enzyme transport: comparison of cation-independent and cation-dependent mannose 6-phosphate receptor-deficient mice. Biochem J 330, 903-908. 28. Jadot, M., Lin, L., Sleat, D. E., Sohar, I., Hsu, M. S., Pintar, J., Dubois, F., Wattiaux-De Coninck, S., Wattiaux, R., and Lobel, P. (1999) Subcellular localization of mannose 6-phosphate glycoproteins in rat brain. J Biol Chem 274, 21104-21113. 29. Sleat, D. E., Gin, R. M., Sohar, I., Wisniewski, K., Sklower-Brooks, S., Pullarkat, R. K., Palmer, D. N., Lerner, T. J., Boustany, R. M., Uldall, P., Siakotos, A. N., Donnelly, R. J., and Lobel, P. (1999) Mutational analysis of the defective protease in classic late-infantile neuronal ceroid lipofuscinosis, a neurodegenerative lysosomal storage disorder. Am J Hum Genet 64, 1511-1523. 30. Sohar, I., Sleat, D. E., Jadot, M., and Lobel, P. (1999) Biochemical characterization of a lysosomal protease deficient in classical late infantile neuronal ceroid lipofuscinosis (LINCL) and development of an enzyme-based assay for diagnosis and exclusion of LINCL in human specimens and animal models. J Neurochem 73, 700-711. 31. Berry-Kravis, E., Sleat, D. E., Sohar, I., Meyer, P., Donnelly, R., and Lobel, P. (2000) Prenatal testing for late infantile neuronal ceroid lipofuscinosis. Ann Neurol 47, 254-257. 32. Naureckiene, S., Sleat, D. E., Lackland, H., Fensom, A., Vanier, M. T., Wattiaux, R., Jadot, M., and Lobel, P. (2000) Identification of HE1 as the second gene of Niemann-Pick C disease. Science 290, 2298-2301. 33. Sohar, I., Lin, L., and Lobel, P. (2000) Enzyme-based diagnosis of classical late infantile neuronal ceroid lipofuscinosis: comparison of tripeptidyl peptidase I and pepstatin-insensitive protease assays. Clin Chem 46, 1005-1008. 34. Tyynela, J., Sohar, I., Sleat, D. E., Gin, R. M., Donnelly, R. J., Baumann, M., Haltia, M., and Lobel, P. (2000) A mutation in the ovine cathepsin D gene causes a congenital lysosomal storage disease with profound neurodegeneration. EMBO J 19, 2786-2792. 35. Lin, L., and Lobel, P. (2001) Production and characterization of recombinant human CLN2 protein for enzyme-replacement therapy in late infantile neuronal ceroid lipofuscinosis. Biochem J 357, 49-55. 37. Lin, L., Sohar, I., Lackland, H., and Lobel, P. (2001) The human CLN2 protein/tripeptidyl-peptidase I is a serine protease that autoactivates at acidic pH. J Biol Chem 276, 2249-2255. 39. Sleat, D. E., Sohar, I., Gin, R. M., and Lobel, P. (2001) Aminoglycoside-mediated suppression of nonsense mutations in late infantile neuronal ceroid lipofuscinosis. Eur J Paediatr Neurol 5 Suppl A, 57-62. 41. Friedland, N., Liou, H. L., Lobel, P., and Stock, A. M. (2003) Structure of a cholesterol-binding protein deficient in Niemann-Pick type C2 disease. Proc Natl Acad Sci U S A 100, 2512-2517. 42. Sleat, D. E., Wiseman, J. A., El-Banna, M., Kim, K. H., Mao, Q., Price, S., Macauley, S. L., Sidman, R. L., Shen, M. M., Zhao, Q., Passini, M. A., Davidson, B. L., Stewart, G. R., and Lobel, P. (2004) A mouse model of classical late-infantile neuronal ceroid lipofuscinosis based on targeted disruption of the CLN2 gene results in a loss of tripeptidyl-peptidase I activity and progressive neurodegeneration. J Neurosci 24, 9117-9126. 43. Sleat, D. E., Wiseman, J. A., El-Banna, M., Price, S. M., Verot, L., Shen, M. M., Tint, G. S., Vanier, M. T., Walkley, S. U., and Lobel, P. (2004) Genetic evidence for nonredundant functional cooperativity between NPC1 and NPC2 in lipid transport. Proc Natl Acad Sci U S A 101, 5886-5891. 44. Sleat, D. E., Lackland, H., Wang, Y., Sohar, I., Xiao, G., Li, H., and Lobel, P. (2005) The human brain mannose 6-phosphate glycoproteome: a complex mixture composed of multiple isoforms of many soluble lysosomal proteins. Proteomics 5, 1520-1532. 47. Cheruku, S. R., Xu, Z., Dutia, R., Lobel, P., and Storch, J. (2006) Mechanism of cholesterol transfer from the Niemann-Pick type C2 protein to model membranes supports a role in lysosomal cholesterol transport. J Biol Chem 281, 31594-31604.



48. Della Valle, M. C., Sleat, D. E., Sohar, I., Wen, T., Pintar, J. E., Jadot, M., and Lobel, P. (2006) Demonstration of lysosomal localization for the mammalian ependymin-related protein using classical approaches combined with a novel density shift method. J Biol Chem 281, 35436-35445. 49. Liou, H. L., Dixit, S. S., Xu, S., Tint, G. S., Stock, A. M., and Lobel, P. (2006) NPC2, the protein deficient in Niemann-Pick C2 disease, consists of multiple glycoforms that bind a variety of sterols. J Biol Chem 281, 36710-36723. 50. Passini, M. A., Dodge, J. C., Bu, J., Yang, W., Zhao, Q., Sondhi, D., Hackett, N. R., Kaminsky, S. M., Mao, Q., Shihabuddin, L. S., Cheng, S. H., Sleat, D. E., Stewart, G. R., Davidson, B. L., Lobel, P., and Crystal, R. G. (2006) Intracranial delivery of CLN2 reduces brain pathology in a mouse model of classical late infantile neuronal ceroid lipofuscinosis. J Neurosci 26, 1334-1342. 51. Sleat, D. E., Wang, Y., Sohar, I., Lackland, H., Li, Y., Li, H., Zheng, H., and Lobel, P. (2006) Identification and validation of mannose 6-phosphate glycoproteins in human plasma reveal a wide range of lysosomal and non-lysosomal proteins. Mol Cell Proteomics 5, 1942-1956. 52. Sleat, D. E., Zheng, H., Qian, M., and Lobel, P. (2006) Identification of sites of mannose 6-phosphorylation on lysosomal proteins. Mol Cell Proteomics 5, 686-701. 53. Tian, Y., Sohar, I., Taylor, J. W., and Lobel, P. (2006) Determination of the substrate specificity of tripeptidyl-peptidase I using combinatorial peptide libraries and development of improved fluorogenic substrates. J Biol Chem 281, 6559-6572. 54. Cabrera-Salazar, M. A., Roskelley, E. M., Bu, J., Hodges, B. L., Yew, N., Dodge, J. C., Shihabuddin, L. S., Sohar, I., Sleat, D. E., Scheule, R. K., Davidson, B. L., Cheng, S. H., Lobel, P., and Passini, M. A. (2007) Timing of therapeutic intervention determines functional and survival outcomes in a mouse model of late infantile batten disease. Mol Ther 15, 1782-1788. 55. Dixit, S. S., Sleat, D. E., Stock, A. M., and Lobel, P. (2007) Do mammalian NPC1 and NPC2 play a role in intestinal cholesterol absorption? Biochem J 408, 1-5. 56. Majumdar, A., Cruz, D., Asamoah, N., Buxbaum, A., Sohar, I., Lobel, P., and Maxfield, F. R. (2007) Activation of microglia acidifies lysosomes and leads to degradation of Alzheimer amyloid fibrils. Mol Biol Cell 18, 1490-1496. 57. Sleat, D. E., Zheng, H., and Lobel, P. (2007) The human urine mannose 6-phosphate glycoproteome. Biochim Biophys Acta 1774, 368-372. 58. Xu, S., Benoff, B., Liou, H. L., Lobel, P., and Stock, A. M. (2007) Structural basis of sterol binding by NPC2, a lysosomal protein deficient in Niemann-Pick type C2 disease. J Biol Chem 282, 23525-23531. 59. Chang, M., Cooper, J. D., Sleat, D. E., Cheng, S. H., Dodge, J. C., Passini, M. A., Lobel, P., and Davidson, B. L. (2008) Intraventricular enzyme replacement improves disease phenotypes in a mouse model of late infantile neuronal ceroid lipofuscinosis. Mol Ther 16, 649-656. 60. Gasingirwa, M. C., Thirion, J., Costa, C., Flamion, B., Lobel, P., and Jadot, M. (2008) A method to assess the lysosomal residence of proteins in cultured cells. Anal Biochem 374, 31-40. 61. Kim, K. H., Pham, C. T., Sleat, D. E., and Lobel, P. (2008) Dipeptidyl-peptidase I does not functionally compensate for the loss of tripeptidyl-peptidase I in the neurodegenerative disease late-infantile neuronal ceroid lipofuscinosis. Biochem J 415, 225-232. 62. Majumdar, A., Chung, H., Dolios, G., Wang, R., Asamoah, N., Lobel, P., and Maxfield, F. R. (2008) Degradation of fibrillar forms of Alzheimer's amyloid beta-peptide by macrophages. Neurobiol Aging 29, 707-715. 63. Qian, M., Sleat, D. E., Zheng, H., Moore, D., and Lobel, P. (2008) Proteomics analysis of serum from mutant mice reveals lysosomal proteins selectively transported by each of the two mannose 6-phosphate receptors. Mol Cell Proteomics 7, 58-70. 64. Sleat, D. E., Della Valle, M. C., Zheng, H., Moore, D. F., and Lobel, P. (2008) The mannose 6-phosphate glycoprotein proteome. J Proteome Res 7, 3010-3021. 65. Sleat, D. E., El-Banna, M., Sohar, I., Kim, K. H., Dobrenis, K., Walkley, S. U., and Lobel, P. (2008) Residual levels of tripeptidyl-peptidase I activity dramatically ameliorate disease in late-infantile neuronal ceroid lipofuscinosis. Mol Genet Metab 94, 222-233. 66. Sun, P., Sleat, D. E., Lecocq, M., Hayman, A. R., Jadot, M., and Lobel, P. (2008) Acid phosphatase 5 is responsible for removing the mannose 6-phosphate recognition marker from lysosomal proteins. Proc Natl Acad Sci U S A 105, 16590-16595. 67. Guhaniyogi, J., Sohar, I., Das, K., Stock, A. M., and Lobel, P. (2009) Crystal structure and autoactivation pathway of the precursor form of human tripeptidyl-peptidase 1, the enzyme deficient in late infantile ceroid lipofuscinosis. J Biol Chem 284, 3985-3997.



68. Kim, K. H., Sleat, D. E., Bernard, O., and Lobel, P. (2009) Genetic modulation of apoptotic pathways fails to alter disease course in tripeptidyl-peptidase 1 deficient mice. Neurosci Lett 453, 27-30. 69. Lubke, T., Lobel, P., and Sleat, D. E. (2009) Proteomics of the lysosome. Biochim Biophys Acta 1793, 625-635. 70. Sleat, D. E., Ding, L., Wang, S., Zhao, C., Wang, Y., Xin, W., Zheng, H., Moore, D. F., Sims, K. B., and Lobel, P. (2009) Mass spectrometry-based protein profiling to determine the cause of lysosomal storage diseases of unknown etiology. Mol Cell Proteomics 8, 1708-1718. Research Support prior three years NIH R01 DK54317 (Peter Lobel, PI) 06/15/99 - 03/31/13 Novel Lysosomal Enzymes and Associated Human Genetic Diseases The major goal of this proposal is to develop and implement a proteomic approach that will result in the identification and characterization of lysosomal proteins and their role in human genetic diseases NIH R01 NS37918 (Peter Lobel, PI) 04/01/98-3/31/09 A Novel Lysosomal enzyme deficient in Batten disease The major goal of this proposal are to develop a transgenic mouse to evaluate therapies for late infantile neuronal ceroid lipofuscinosis and the role of tripeptidyl peptidase 1 (TPP1) in Alzheimer disease and to evaluate new modes of delivery and use of modified TPP1 derivatives for brain enzyme replacement therapy. NIH S10 RR024584A1 (Peter Lobel, PI) 41/09-3/31/10 High resolution LC-MS/MS system This is a shared instrument grant proposal to obtain an Orbitrap ETD mass spectrometer the RWJMS-Rutgers Biological Mass Spectrometry Facility. Ara Parseghian Medical Research Foundation (Peter Lobel, PI) 07/01/01 -6/30/10 Molecular Characterization of Niemann Pick C2 Disease The major goal of this proposal is to better understand the biological and biophysical properties of the protein that is deficient in Niemann-Pick type C2 disease. NJ Commission of Science and Technology, (ExSAR Corporation, PI) 07/01/07 -6/30/09 Edison Innovation R&D Fund Award This is a grant to the mass spectrometry facility that I head. The major goal is to develop a MALDI-TOF based hydrogen-deuterium exchange strategy to screen small molecule libraries for molecules that stabilize proteins Sponsored research (Peter Lobel, PI) 1/1/08-6/30/09 BioMarin Pharmaceuticals, Inc. This is a research contract to provide reagents and analytical support for enzyme replacement therapy preclinical studies.



NAME Jianjie Ma eRA COMMONS USER NAME Jianjie_Ma




Wuhan University (China) B.S. 1983 Physics Baylor College of Medicine Ph.D. 1986-1989 Physiology and Biophysics Rush Medical College Postdoctoral 1989-1992 Physiology and Biophysics


Positions and Employment 2009 - Acting Chair, Dept. of Physiology and Biophysics, Robert Wood Johnson Medical School 2008 - Professor, Department of Medicine, Robert Wood Johnson Medical School 2008 - Chief, Division of Developmental Medicine & Research, Robert Wood Johnson Medical School 2007 - Founder & CEO, TRIM-edicine, Inc. 2001 - University Professor, Dept. of Physiology & Biophysics, Robert Wood Johnson Medical School 2002 - Founder and Director, Graduate Program in Physiology and Integrative Biology Joint Program between UMDNJ and Rutgers University 2006 - Guest Professor, Institute of Molecular Medicine, Peking University 1997-2001 Associate Professor, Department of Physiology and Biophysics Case Western Reserve University (CWRU) 1992-1997 Assistant Professor, Department of Physiology and Biophysics, CWRU

Awards and Other Professional Activities Established Investigator of American Heart Association (1994-1999) Research Fellow, Japan Society for the Promotion of Sciences (1999-2000) University Named Professor (2001 - ) - University of Medicine and Dentistry of New Jersey Editorial Board Member of the Journal of Biological Chemistry (2002 – 2008) Editorial Board Member for Cell Research (2002 - present) Editorial Board Member for Current Chemical Biology (2006 – present) Editorial Board Member for Journal of Biophysics (2008 - present) Outstanding Young Investigator Award from Chinese Natural Science Foundation (2007-2010) NIH Study Section, Chartered Member on NTRC (2002-2006), NIDDK B-Committee (2004 - present) Special Emphasis Panel for NIDDK Program Project Review (2001, 2002) Special Emphasis Panel for NIA Program Project Review (2005, 2006, 2007) Special Emphasis Panel for NCCAM Program Project Review (2006, 2007)

Selected Research Speaker to the Annual Meeting of Associations of Chairs for Department of Physiology (2009)

Member of the Global Musculoskeletal Experts Forum – Merck Co. (2009)

B. Selected peer-reviewed publications (since 2008) 42. Zhang Q, Hong M, Duan P, Pan Z, Ma J, You G. (2008) Organic Anion transporter OAT1 Undergoes

constitutive and protein kinase C-regulated trafficking through a Dynamin- and Clathrin-dependent pathway. J Biol Chem. 283: 32570-9.

43. Liu QH, Zheng YM, Korde AS, Li XQ, Ma J, Takeshima H, Wang YX. (2008) Protein kinase C-{epsilon} regulates local calcium signaling in airway smooth muscle cells. Am J Respir Cell Mol Biol. Nov 14. [Epub ahead of print]

44. Li XQ, Zheng YM, Rathore R, Ma J, Takeshima H, Wang YX. (2008) Genetic evidence for functional role of ryanodine receptor 1 in pulmonary artery smooth muscle cells. Pflugers Arch. Jul 29. [Epub ahead of print]

45. Cai, C., Masumiya, H., Weisleder, N., Nishi, M., Komazaki, S., Ko, J.K., Lin, P., Thornton, A., Pan, Z., Brotto, M., Takeshima, H., and Ma, J. (2009) MG53 nucleates assembly of cell membrane repair machinery. Nature Cell Biology 11: 56-64.

46. Cai C, Masumiya H, Weisleder N, Pan Z, Nishi M, Komazaki S, Takeshima H, Ma J. (2009) MG53 regulates membrane budding and exocytosis in muscle cells. J. Biol. Chem. 284: 3314-3322.

47. Masumiya H, Asaumi Y, Nishi M, Minamisawa S, Adachi-Akahane S, Yoshida M, Kangawa K, Ito K, Kagaya Y, Yanagisawa T, Yamazaki T, Ma J, Takeshima H. (2009) Mitsugumin 53-mediated maintenance of K+ currents in cardiac myocytes. Channels 3: 6-11.

48. Weisleder, N, Takeshima, H and Ma, J. (2009) MG53 facilitates vesicle trafficking in striated muscle to contribute to cell membrane repair. Communicative Integrative Biology (in press).

49. Cai C, Weisleder N, Ko JK, Komazaki S, Sunada Y, Nishi M, Takeshima H, Ma J. (2009) Membrane repair defects in muscular dystrophy are linked to altered interaction between MG53, caveolin-3 and dysferlin. J. Biol. Chem. 2009 Apr 20. [Epub ahead of print] (paper of the week)

50. Liang, X, Parness, J., Fruen, B., Hu, J., Hu, X. Ma, J. (2009) Tight coupling of skeletal muscle ryanodine receptors is abrogated in malignant hyperthermia. Biophys. J. (in review).

51. Li, N., Lin, P., Cai, C., Pan, Z., Weisleder, N, and Ma, J. (2009) The amino-terminal peptide of Bax perturbs intracellular Ca2+ homeostasis to enhance apoptosis in prostate cancer cells. Am. J. Physiol (Cell) 296: C267-72.

52. Calcraft, P.J., Ruas, M. Pan, Z, Cheng, X, Arredouani, A., Hao, X, Tang, J., Rietdorf, K. Teboul, L., Chuang, KT Lin, P, Xiao, R, Wang, C, Zhu, Y., Lin, Y, Wyatt, CN, Parrington, J, Ma, J, Evans, AM, Galione, A, Zhu, M.X. (2009) NAADP mobilizes calcium from acidic organelles through two-pore channels. Nature (published online on April 22, 2009).

53. Galione, A., Evans, A.M., Ma, J., Parrington, J., Arredouani, A., Cheng, X., Zhu, M. (2009) The acid test: the discovery of two pore channels (TPCs) as NAADP-gated endo-lysosomal Ca release channels. Pflugers Arch. (in press).

54. Woo JS, Hwang JH, Ko JK, Kim DH, Ma J, Lee EH. (2009) Glutamate at position 227 of junctophilin-2 is involved in binding to TRPC3. Mol Cell Biochem. 2009 Mar 10. [Epub ahead of print].

C. Research Support. Active: RO1-CA95739 (PI) 8/1/01 – 3/31/11 Store-operated Ca entry and apoptosis The major goal of this project is to examine the role of store-operated Ca entry in apoptosis of prostate cells. RO1-AG28614 (PI) 7/1/06 – 6/30/11 Ca sparks in muscle aging and dystrophy The goal of this project is to study the hypothesis that stress-induced Ca sparks are a representation of the normal physiological response of healthy skeletal muscle, whose dysfunction can contribute to pathophysiology of muscular dystrophy and aging-associated decreases in muscle function. RO1-HL69000 (PI) 12/1/06 – 11/30/11 Bi-directional Ca Signaling in Striated Muscle Cells The goals of this project are to explore the role of MG53 in determining the orthograde regulation of intracellular Ca release and retrograde regulation of store-operated Ca entry in skeletal muscle. RO1-AG028856 (PI) 3/15/08 – 2/28/13 TRIC, a Novel Modulator of Intracellular Ca Homeostasis The goals of this project are to elucidate the function of TRIC as a counter-ion channel associated with release of Ca from intracellular stores. There is no overlap of this project with our proposed studies.

BIOGRAPHICAL SKETCH

NAME: Madura, Kiran POSITION TITLE

eRA COMMONS USER NAME:

Professor

EDUCATION INSTITUTION AND LOCATION DEGREE YEAR FIELD OF STUDY

Ithaca College, Ithaca, NY BS 1981 Biology

University of Rochester, Rochester, NY PhD 1989 Biology

PROFESSIONAL EXPERIENCE 1984-1989 Doctoral Dissertation with Dr. S. Prakash, Univ. of Rochester, Rochester, NY 1989-1992 American Cancer Society Postdoctoral Fellow in the laboratory of Dr. A. Varshavsky, Massachusetts Institute of Technology, Cambridge, MA 1992-1994 Research Fellow with Dr. A. Varshavsky at California Institute of Technology 1994- 2001 Assistant Professor, Department of Biochemistry, RWJMS, Piscataway, NJ. 2001-2006 Associate Professor, Department of Biochemistry, RWJMS, Piscataway, NJ. 2001-present Director, Program in Biochemistry and Molecular Biology. 2006-present Professor, Department of Biochemistry, RWJMS, Piscataway, NJ. AWARDS 1987-1988 Elon Huntington Hooker Fellowship, University of Rochester 1987 Genetics Society of America Graduate Student Award. 1989-1991 American Cancer Society Postdoctoral Fellow, Massachusetts Institute of Technology SERVICE 2001-2002 Reviewer, Ad-hoc NIH/RAD Study Section 2003-2004 Reviewer, Ad-hoc NSF 2002, 2003 Reviewer, Ad-hoc United States-Israel Binational Science Foundation 2001-present Judge Siemens-Westinghouse Science & Technology Competition 2002-2006 Member, Permanent NIH/RTB Study Section (2002-2006) 2007-present Reviewer, Ad-hoc NOMD Study Section (full member from 2008-2012) CURRENT ACADEMIC APPOINTMENTS Professor of Biochemistry, Department of Biochemistry, Robert Wood Johnson Medical School-UMDNJ. Adjunct Faculty, Graduate Program in Biochemistry, Rutgers University. Adjunct Faculty, Graduate Program in Microbiology, Rutgers University. Director, Graduate Program in Biochemistry and Molecular Biology. Member, The Cancer Institute of New Jersey, Member, NIEHS Center for Environmental and Occupational Health Sciences Institute. PUBLICATIONS 26. Ortolan, T. G., Chen, L., Tongaonkar, P. and Madura, K. (2004). Rad23 stabilizes Rad4 from

degradation by the Ub/proteasome pathway. Nuc. Acids Res. 34: 1-11. 27. Chuang, S-M., Chen, L., Lambertson, D., Anand, M., Kinzy, T. G. and Madura, K. (2005).

Proteasome-mediated degradation of co-translationally damaged proteins involves the translation elongation factor eEF1A. Mol. Cell. Biol. 25: 403-413.

28. Doss-Pepe, E., Chen, L. and Madura, K. (2005). Alpha-Synuclein and Parkin contribute to the assembly of ubiquitin lysine63-linked multiubiquitin chains. J Biol Chem., 280:16619-24.

29. Chen, L. and Madura, K. (2005). Increased proteasome activity, ubiquitin-conjugating enzymes and eEF1A translation factor detected in breast cancer tissue. Cancer Res., 65: 5599-5606.

30. Chuang, S-M. and Madura, K. (2005). Ub-conjugating enzyme Ubc4 binds the proteasome in the presence of translationally-damaged proteins. Genetics 171: 1477-1484.

31. Chen, L., Thiruchelvam, M. J., Madura, K. and Richfield, E. (2006). Proteasome Dysfunction in Aged Human alpha-Synuclein Transgenic Mice. Neurobiology of Disease. 1: 120-126.

32. Chen, L. and Madura, K. (2006). Evidence for Distinct Functions for Human DNA Repair Factors hHR23A and hHR23B. FEBS Letters. 580: 3401-3408.

33. Depre, C., Wang, Q., Yan, L., Hedhli, N., Peter, P., Chen, L., Hong, C., Hittinger, L., Ghaleh, B., Sadoshima, J., Vatner, D. E., Vatner, S. F. and Madura, K. (2006). Activation of the cardiac proteasome during pressure overload promotes ventricular hypertrophy. Circulation 114: 1821-1828.

34. Romero-Perez, L., Chen, L., Lambertson, D. and Madura, K. (2007) Sts1 can overcome the loss of Rad23 and Rpn10 and represents a novel regulator of the ubiquitin/proteasome pathway. Journal of Biological Chemistry 282: 35574-35582.

35. Hedhli, N., Wang, Q., Yan, L., Chen, L., Hong, C., Chen, W., Pelat, M., Lagunoff, D., Vatner, S. F., Madura, K. and Depre, C. (2007) Activation and nuclear translocation of proteasome during myocardial hypertrophy by the stress-response protein H11 Kinase. Circulation Research. 77: 497-505.

36. Hedhi, N., Wang, L., Wang, Q., Rashed, E., Tian, Y., Sui, X., Madura, K and Depre, C. (2008) Proteasome activation during cardiac hypertrophy by the chaperone H11 Kinase/Hsp22. Cardiovasc. Res. 77: 497-505.

37. Chen, L. and Madura, K. Centrin/Cdc31 is a novel regulator of protein degradation. (2008) Molecular and Cellular Biology 28: 1829-1840.

38. Hedhli N, Lizano P, Hong C, Fritzky LF, Dhar SK, Liu H, Tian Y, Gao S, Madura K, Vatner SF, Depre C. (2008) Proteasome inhibition decreases cardiac remodeling after initiation of pressure overload. J Physiol Heart Circ Physiol. 295(4):H1385-93.

39. Geetha T, Seibenhener ML, Chen L, Madura K, Wooten MW. (2008) p62 serves as a shuttling factor for TrkA interaction with the proteasome. Biochem Biophys Res Commun. 374(1):33-7.

40. Madura, K. (2009) The Proteasome assembly line. Nature 459: 787-788. ACTIVE GRANTS 1. “Functional Analysis of Rad23 Protein” Principal Investigator: Kiran Madura Agency: NIH/NCI Type: R01-CA83875 Period: 08/01/00 – 07/30/11 Total Cost: $1,484,000 2. Studies to examine Centrin's role in DNA repair Principal Investigator: Kiran Madura Agency: NIH/NIGMS Type: 1R01-GM083321-01 Period: 10/15/07 – 10/14/11 Total Cost: $1,250,000 3. Graduate Training in Cellular and Molecular Biology

(The PI administers graduate training fellowships in the Department of Biochemistry. ) Principal Investigator: Kiran Madura Agency: NIH/NIGMS Type: T32-GM008360 Period: 07/1/07 - 06/30/12 Total Cost: $345,000




https://commons.era.nih.gov/commons/genericStatus.do?actionRole=nonPI&applID=7350609&uhf-token=AXoDEXQlmXdM2NLDdPqf%2BK%2FnNn8%3D

Curriculum Vitae – Charles E. Martin

Education:

B.S. in Zoology, University of Illinois, 1966 Ph.D. in Biochemical Genetics, Florida State University, 1972 A. Gib DeBusk, Advisor Employment: 1972-1974 Postdoctoral Associate, University of Texas at Austin, 1974-1978 Postdoctoral Associate, University of Texas at Austin, 1978-1984 Assistant Professor of Biology, Rutgers University 1984-1994 Associate Professor of Biology, Rutgers University 1989-1990 Visiting Associate Professor, Princeton University 1994-present Professor of Cell Biology and Neuroscience, Rutgers University 1994-1995 Associate Director, Bureau of Biological Research, Rutgers University 1996-present Director, Bureau of Biological Research, Rutgers University 1996-present Director, Molecular Biosciences Graduate Programs, Rutgers University 2007-present Director of Education, Division of Life Sciences, Rutgers University Awards and Honors 1972-1975 National Institutes of Health Postdoctoral Fellow 1993-1994 Excellence in Graduate Teaching Award, The Graduate School, Rutgers

Univ. 1999-2004 Member, Journal of Biological Chemistry Editorial Board 2005 Vice-Chair, Gordon Conference on Molecular and Cellular Biology of

Lipids 2007 Chair, Gordon Conference on Molecular and Cellular Biology of Lipids 2007-present Member, Journal of Biological Chemistry Editorial Board Teaching: Undergraduate: General Biology, Genetics, Biology and Society (non-majors), Membrane Biology Graduate: Cell and Molecular Biology, Molecular Genetics, Membrane Biology, Quantitative Problems in Molecular Biology Participation in Teaching Conferences: American Society for Cell Biology, Education workshops (1996, 2001 – 2007) , American Society for Biochemistry and Molecular Biology teaching workshops) 2004, 2005, 2006), Professional Science Master’s Association meeting (2007), AAAS/NSF Conference on Transforming Undergraduate Education in Biology (2009)

Selected Publications: Book: BIOLOGY, 1989, Sanders College Publishing, 1200+ pages, with C. Villee, D. Martin, E. Solomon, and L. Berg. A first year general biology text with an international distribution. Translated into Spanish, Polish, and Korean.

Selected Refereed Publications: Kandasamy, P., Vemula, M, Oh. C.S., Chellappa, R., Martin, C.E. Regulation of Unsaturated Fatty Acid Biosynthesis in Saccharomyces. The ER membrane protein, Mga2p, a transcription activator of the OLE1 gene, regulates the stability of the OLE1 mRNA through exosome-mediated mechanisms. J. Biol. Chem (2004) 279: 36586 - 36592 .Boumann, H.A. Gubbens, J., Koorengevel, M.C. Oh, C-S, Martin, C.E., Heck, A.J.R., Patton-Vogt, J. Henry, S.A., de Kruijff, B. and A. I.P.M. de Kroon. Depletion of phosphatidylcholine in yeast induces shortening and increased saturation of the lipid acyl chains. Evidence for regulation of intrinsic membrane curvature in a eukaryote. (2006) Mol. Biol. Cell 17:1006-1017 Oh, C-S and Martin, C.E. Candida albicans Spt23p controls the expression of the Ole1p Δ9 fatty acid desaturase and regulates unsaturated fatty acid biosynthesis. J. Biol. Chem.281 (2006) 7030-7039. Martin, C.E., C.S. Oh and Y. Jiang (2007) Regulation of long chain unsaturated fatty acid synthesis in yeast., Biochim Biophys Acta 1771: 271-85. Xu,D. Sillaots, S., Davison, J., Hu, W. Jiang, B., Kauffman, S., Martel, N., Ocampo, P., Oh, C.S., Veillette, K., Wang, H., Yang, M., Zhang, L., Becker, J., Martin, C.E. and T. Roemer (2009) Chemical Genetic Profiling and Characterization of Small-molecule Compounds That Affect the Biosynthesis of Unsaturated Fatty Acids in Candida albicans Journal of Biological Chemistry (2009) 284: 19754-19764 Patents: PATENT #5,057,419, Awarded Oct. 15, 1991, “Genetically Engineered Plasmid and organisms for the Production of Specialized Oils”. Patent #6,825,335 Awarded November 30, 2004 “Synthetic Fatty Acid Desaturase Gene for Expression in Plants: External Funding: NIH 2R01 GM45768 Regulation of Fatty Acid Metabolism (1996 -2007)

1

BIOGRAPHICAL SKETCH NAME

Michael P. Matise, Ph.D.

POSITION TITLE

Associate Professor of Neuroscience & Cell Biology EDUCATION/TRAINING



University of Rochester, New York

B.S. 1982-1986 Neuroscience

University of Pittsburgh, Pennsylvania Ph.D. 1988-1994 Neurobiology & Cell Science

Skirball Institute, NYU Medical Center, N.Y., N.Y. Post-Doc 1994-1999 Developmental Genetics

A. Positions and Honors. Positions and Employment 1984–1986 Undergraduate Research Student, University of Rochester, New York 1998–1994 Graduate Student, University of Pittsburgh, Pennsylvania 1994–2000 Post Doctoral Fellow, Skirball Institute, NYU Medical Center 2000–2008 Assistant Professor, Dept. of Neuroscience & Cell Biology, UMDNJ/RWMJS 2006-present Associate Member, Child Health Institute of NJ 2006-present Member, Cancer Institute of NJ 2008-present Associate Professor, Dept. of Neuroscience & Cell Biology, UMDNJ/RWMJS Other Experience and Professional Memberships 1992—present Member, Society for Neuroscience 1997—present Member, Society for Developmental Biology Honors 1986 B.S. with distinction in research, University of Rochester 1991–1993 NRSA Pre-doctoral training grant in Developmental Neuroscience 1996–1998 NRSA Post-doctoral training grant in Developmental Neuroscience 1999 WCBR Fellowship, 32nd Annual Conference in Snowmass, CO 2002-2004 Basil O’Connor Research Scholar (March of Dimes) B. Selected peer-reviewed publications (in chronological order). Articles Lei, Q., Zelman, A.K., Kuang, E., Li, S., and Matise, M.P. (2004). Transduction of graded Hedgehog

signaling by a combination of Gli2 and Gli3 activator functions in the developing spinal cord. . Development 131, 3593.

Li, H, Misra, K., Matise, M.P.*, and Xiang, M.* (2005). Foxn4 Acts Synergistically with Mash1 to Specify

Subtype Identity of V2 Interneurons in the Spinal Cord. PNAS 102, 10689. (*co-senior author).

2

Dillon, A.K., Fujita, S.C., Matise, M.P., Jarjour, A.A., Kennedy, T.E., Kollmus, H., Arnold, H.H., Weiner, J.A., Sanes, J.R, and Kaprielian, Z. (2005). Molecular Control of Spinal Accessory Motor Neuron/Axon Development in the Mouse Spinal Cord. The Journal of Neuroscience 25, 10119-30.

Kadison, S.R., Murakami, F., Matise, M.P., and Kaprielian, Z. (2006). The role of floor plate contact in the elaboration of contralateral commissural projections within the embryonic mouse spinal cord. Developmental Biology 296, 499-513.

Lei, Q., Jeong, Y., Misra, K., Li, S., Zelman, A.K., Epstein, D.J, and Matise, M.P. (2006). Wnt signaling inhibitors regulate the transcriptional response to morphogenetic Shh-Gli signaling in the neural tube. Developmental Cell 11 (3), 325-337.

Gui, H., Li, S. and Matise, M.P. (2007). A cell-autonomous requirement for Cip/Kip Cyclin-kinase inhibitors in regulating the timing of neuronal cell cycle exit but not differentiation in the developing spinal cord. Developmental Biology 301. 14-26.

Misra, K.P., Gui, H., and Matise, M.P. (2008). Prox1 regulates a transitory state for interneuron neurogenesis in the spinal cord. Developmental Dynamics 237, 393-402.

Misra, K.P. and Matise, M.P. (2010). A critical role for sFRP proteins in maintaining caudal neural tube closure in mice via inhibition of BMP signaling. Developmental Biology 337(1):74-83

C. Research Support Ongoing Research Support 1) NSF 0744626 Matise (PI) 3/15/08—2/28/11 1.8 mo (CY) National Science Foundation Molecular Regulation of Hedgehog Signaling by Gli Factors Total Costs: $450,000 2) R01 HD057015 Matise (PI) 7/01/09–6/30/11 6 mo (CY) NIH/NICHD Molecular control of Shh-Gli signaling in the vertebrate CNS Role:Principal Investigator Total Costs: $865,760 3) NJCSCR Matise (PI) 12/15/2009-12/30/2011 1.2 mo (CY) Signaling pathways regulating axon remyelination Total Costs: $400,000 Past Support (3 years) 1) National Science Foundation: “Molecular Control of Shh/Gli Signalling in the Vertebrate CNS” 02/01/02—6/30/07 Direct Costs: $520,000 Role: Principal Investigator 2) NJCSCR: “Molecular Control of Spinal Cord Neuronal Progenitor Differentiation 12/15/04—12/30/07 Direct Costs: $400,000 Role: Principal Investigator 3) NIH/NIMH: “Molecular regulation of Neurogenesis and Cell Fate” 7/01/03–6/30/09 Direct Costs: $1,613,315 Role: Principal Investigator





NAME

Tara C. Matise eRA COMMONS USER NAME

matiset

POSITION TITLE

Associate Professor



Cornell University, Ithaca, NY B.S. 1986 Biology/Genetics Univ. of Pittsburgh, Pittsburgh, PA M.S. 1988 Human Genetics Univ. of Pittsburgh, Pittsburgh, PA Ph.D. 1992 Human Genetics

A. Positions and Honors. Positions and Employment 1992-1994 Postdoctoral Fellow, W.M. Keck Center for Advanced Training in Computational Biology, University of Pittsburgh, PA 1994-1996 Postdoctoral Fellow, Dept. of Psychiatry, Columbia University, NY 1996-1997 Postdoctoral Fellow, Lab. of Statistical Genetics, The Rockefeller University, NY 1997-2000 Assistant Professor, Lab. of Statistical Genetics, The Rockefeller University, NY 2000–2002 Associate Research Professor, Department of Genetics, Rutgers University, NJ 2002–2009 Associate Professor, Department of Genetics, Rutgers University, NJ 2009– Associate Professor (tenured), Department of Genetics, Rutgers University, NJ Other Experience and Professional Memberships 1995-pres. Instructor: Basic and Advanced Linkage Course, Columbia University and Rockefeller University 1998-2004 Member, Board of Scientific Counselors, NIH National Center for Biotechnology Information 1999-pres. Ad hoc reviewer: USDA, NIH/MGN, NIH/SSS-Y, NIH/NIEHS, NIH/NHLBI, NIH/GCAT, NIH/GNM 2005-2008 Member, NIH/CIDR-R Access Committee Review Panel Honors 1990 Honored by the Cystic Fibrosis Foundation 1993 Outstanding Student Award, University of Pittsburgh B. Selected peer-reviewed publications (partial listing from 76). Kaufmann CA, Suarez B, Malaspina D, Pepple J, Svrakic D, Markel PD, Meyer J, Zambuto CT, Schmitt K, Matise TC,

Harkavy-Friedman JM, Hampe C, Lee H, Schore D, Wynne D, Moldin S, Faraone SV, Tsuang MT, Cloninger CR (1998) The NIMH Genetics Initiative Millennium Schizophrenia Consortium: linkage analysis of African-American pedigrees. Neuropsychiatric Genetics 81:282-289

Gordon D, Matise TC, Heath SC, Ott J. 1999 Power loss for multiallelic transmission disequilibrium tests when errors introduced: GAW 11 simulated data. In: Goldin L, Amos CI, Chase GA, Goldstein AM, Jarvik GP, Martinez MM, Suarez BK, Weeks DW, Wijsman EM, and MacCluer JW. Genetic Analysis Workshop 11: Analysis of genetic and environmental factors in common diseases. Genetic Epidemiology, 17:S587-S592

Puca AA, Daly MJ, Brewster SJ, Matise TC, Barrett J, Shea-Drinkwater M, Kang S, Joyce E, Nicoli J, Benson E, Kunkel LM, Perls T. (2001) A genome-wide scan for linkage to human exceptional longevity identifies a locus on chromosome 4. PNAS 98(18):10505-10508).

Brunak S, Danchin A, Hattori M, Nakamura H, Shinozaki K, Matise T, Preuss D. 2002. Nucleotide sequence database policies. Science (Letter) 298:1333.

Clark AG, Nielsen R, Signorovitch J, Matise TC, Glanowski S, Heil J, Winn-Deen ES, Holden AL, Lai E. 2003. Linkage disequilibrium and inference of ancestral recombination in 538 single-nucleotide polymorphism clusters across the human genome. Am J Hum Genet 73:285-300.

Majewski J, Schultz DW, Weleber RG, Schain MB, Edwards AO, Matise TC, Acott TS, Ott J, Klein ML. 2003. Age-related macular degeneration--a genome scan in extended families. Am J Hum Genet 73:540-50.

Kim D.D., T.T. Kim, T. Walsh, Y. Kobayashi, T.C. Matise, S. Buyske, and A. Gabriel. (2004) Widespread RNA editing of embedded alu elements in the human transcriptome. Genome Res, 14(9): 1719-25.

Principal Investigator/Program Director (Last, First, Middle): Matise, Tara C.

PHS 398/2590 (Rev. 09/04, Reissued 4/2006) Page Continuation Format Page

Buyske S, Bates M, Gharani N, Matise TC, Tischfield J. 2006. Cognitive Traits link to Human Chromosomal Regions. Behavior Genetics 36(1):65-76.

Matise, TC, Chen F, Chen W, De La Vega FM, Hansen M, He C, Hyland FCL, Kennedy GC, Kong X, Murray SS, Ziegla JS, Stewart WCL, Buyske S. 2007. Second-generation combined linkage-physical maps. Genome Research 17: 1783-1786.

Buyske, S, Yang, G, Matise, TC, Gordon, D. 2008. When a case is not a case. Hum Hered. 2009 67(4):287-292. Chen C, Yang G, Buyske T, Matise TC, Finch SJ, Gordon D. (2009) Transmission disequilibrium test power and sample

size in the presence of locus heterogeneity. Stat Appl Genet Mol Biol. 2009;8(1): Article 44. Epub 2009 Oct 8. Clark AC, Xu W, Matise TC. Contrasting methods of quantifying fine structure of human recombination. Annual Reviews:

Annual Review of Genomics and Human Genetics, Volume 11 (invited review, submitted 1/2010). C. Research Support Ongoing Research Support HHSN271200900012C (Tischfield, co-I Matise) 4/09 - 4/12 0 academic 1,

summer NIH/NIDA $6,757,729 NIDA Center for Genetics Studies The major goals of this project are to maintain a transformed Lymphocyte cell line (LCL) repository of viable cells from individuals with addiction disorders in frozen storage, extract DNA and distribute for NIDA. U24MH068457 (Tischfield, co-I Matise) 9/08-9/13 2.7 academic NIH/NIMH $39,416,147 NIMH Center for Collaborative Genetic Studies on Mental Disorders The major goals of this project are of this competetive renewal are to maintain a transformed LCL repository from individuals with various mental disorders, extract DNA and distribute to NIMH-approved researchers, and develop new analytic methods for genetic data from the NIMH genetics initiative. HHSN267200800018C (Tischfield, co-I Matise) 7/08-7/13 1.35 academic NIH/NIDDK $9,915,124 NIDDK Genetics Repository The major goals of this project are of this competetive renewal are cell transformation and related services. U01 HG004801-01 (Matise) 7/08 - 6/12 0.45 academic 2,

summer NIH/NHGRI $2,653,053 NHGRI EpiGenVar Coordinating Center The major goals of this project are to manage data retrieval, synthesis, and dissemination for the NIH initiative on “Epidemiologic Investigation of Putative Causal Genetic Variant. U01 HG004801-02S1 (Matise) 9/09-8/11 NIH/NHGRI $398,864 NHGRI EpiGenVar Coordinating Center The major goals of this project are AIMS, HapMap, Metabochip Pilot. Busch Funds (Matise) 7/08-6/10 0.45 academic Rutgers University $25,000 Genomic Characterization of Schizophrenia Candidate Gene Regions The major goals of this project are to define schizophrenia candidate regions based on linkage scans, and characterize and evaluate these regions to create a prioritized set of likely candidate genes for schizophrenia. R01 GM080221 (Matise) 7/07 - 6/11 0.9 academic NIH/NIGMS $300,000 The Rutgers Mapping Resources The major goals of this project are to develop, maintain and support the Rutgers Mapping Resources.

Principal Investigator/Program Director (Last, First, Middle): Matise, Tara C.


R03 HD051743 (Matise) 5/07 – 4/09 1.7 academic NIH/NICHD $100,000 The Genetics of Female Reproductive Aging The major goals of this project are to complete the collection of a population-based sample for quantitative trait analysis of genes that control female reproductive aging; to test this sample for allelic association with several candidate genes.

BIOGRAPHICAL SKETCH

NAME Kim S. McKim





Simon Fraser University B.Sc. 1981-86 Biology University of British Columbia Ph.D. 1986-1990 Genetics

A. Positions

September 1986 - December 1990: Doctoral research with Dr. Ann Rose, Department of Medical Genetics, University of British Columbia, Vancouver, B.C. January 1991 - December 1991: Postdoctoral research with Dr. D. L. Baillie, Institute of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby B.C. January 1992 - October 1996: Postdoctoral research with Dr. R. Scott Hawley, Section of Molecular and Cellular Biology, University of California, Davis CA. November 1996 - present: Assistant Professor, Waksman Institute, Department of Genetics, Rutgers University, Piscataway NJ. July 2003 - present: Associate Professor, Waksman Institute, Department of Genetics, Rutgers University, Piscataway NJ. B. Selected peer-reviewed publications (in chronological order).

Manheim E. A. and K. S. McKim, 2003 C(2)M, a novel component of the synaptonemal complex, regulates meiotic crossing over. Curr. Biol. 13: 276-285 Sherizen, D.E., R. Bhagat, J.K. Jang and Kim S. McKim, 2003 Relationship of DNA double-strand breaks to synapsis in Drosophila. J. Cell Science 116: 3069-3077 R. Bhagat, E. A. Manheim, D. E. Sherizen and K. S. McKim, 2004 Studies on crossover specific mutants and the distribution of crossing over in Drosophila females. Cytogenet Genome Res 2004 107: 160-171 Sherizen, D.E., J.K. Jang, N. Kato, and K. S. McKim, 2005 Translocations are dominant meiotic crossover suppressors due to a defect early in the recombination pathway. Genetics 169: 767-81 Gong, W.J, K.S. McKim and R.S. Hawley RS, 2005 All Paired Up with No Place to Go: Pairing, Synapsis, and DSB Formation in a Balancer Heterozygote. PLoS Genet: 1: 589 - 602 McKim, K.S., 2005 When Size Does Not Matter: Pairing Sites during Meiosis. Cell: 123(6):989-92. Jang, J.K., T. Rahman and K. S. McKim, 2005 The kinesinlike protein subito contributes to central spindle assembly and organization of the meiotic spindle in Drosophila oocytes. Mol. Biol. Cell.: 16:4684-4694 Dorsett D., J.C. Eissenberg, Z. Misulovin, A. Martens, B. Redding and K.S. McKim, 2005 Effects of sister chromatid cohesion proteins on cut gene expression during wing development in Drosophila. Development: 132:4743-4753 Anderson, L.K., S.M. Royer, S.L. Page, K.S. McKim, A. Lai, M.A. Lilly and R.S. Hawley, 2005 Juxtaposition of C(2)M and the transverse filament protein C(3)G within the central region of Drosophila synaptonemal complex. Proc. Natl. Acad. Sci. USA: 102:4482-4487

Cesario, J., B. Redding, N. Shah, T. Rahman, J.K. Jang and K. S. McKim, 2006 Kinesin 6 family member, helps to assemble the mitotic spindle and interacts with mitotic regulators such as Polo kinase and the Passenger proteins. J. Cell Sci., in revision Mehrotra, S. and K.S. McKim, 2006 Temporal Analysis of Meiotic DNA Double-Strand Break Formation and Repair in Drosophila Females. PLoS Genet. 2: 1883-1897 McKim, K.S, 2007 Meiotic Pairing: A Place to Hook up. Curr Biol. 17:R165-8 Joyce E.F. and K.S. McKim, 2007 When specialized sites are important for synapsis and the distribution of crossovers. Bioessays 29: 217-26 Mehrotra, S., R. S. Hawley and K. S. McKim, 2007 Synapsis, double strand breaks and domains of crossover control in females, pp. 125-152 in Recombination and meiosis, crossing-over and disjunction, edited by R. Egel and D. Lankenau. Springer-Verlag, Berlin. Jang, J.K., T. Rahman, V.S. Kober, J. Cesario and K.S. McKim 2007 Misregulation of the Kinesin-like protein Subito induces meiotic spindle formation in the absence of chromosomes and centrosomes. Genetics 177: 267-280. Doubilet S., and K.S. McKim 2007 Spindle assembly in the oocytes of mouse and Drosophila - similar solutions to a problem. Chromosome Res. 15: 681-96. Trowbridge K, K. McKim, S.J. Brill and J. Sekelsky, 2007 Synthetic lethality in the absence of the Drosophila MUS81 endonuclease and the DmBlm helicase is associated with elevated apoptosis. Genetics 176: 1993-2001. Colombie, N., C. F. Cullen, A. L. Brittle, J. K. Jang, W. C. Earnshaw, M. Carmena, K. S. McKim and H. Ohkura, 2008 Dual roles of Incenp critical to the assembly of the acentrosomal metaphase spindle in female meiosis, Development, 135:3239-46. Wu, C., V. Singaram and K. S. McKim, 2008, mei-38 is required for chromosome segregation during meiosis in Drosophila females, Genetics, 180:61-72 McKim, K. S., E. F. Joyce and J. K. Jang, 2009 Cytological analysis of meiosis in fixed Drosophila ovaries in the Methods in Molecular Biology, S. Keeney (Ed). Humana Press, Totowa, NJ, in press Joyce, E. F. and K. S. McKim, 2009 Drosophila PCH2 is required for a pachytene checkpoint that monitors DSB-independent events leading to meiotic crossover formation. Genetics, 181(1):39-51. Joyce, E.F., N. S. Tanneti and K. S. McKim, 2009 Drosophila HDM protein is required for a subset of meiotic crossovers and interacts with repair endonuclease complex subunits MEI-9 and ERCC1. Genetics, 181:335-40 c. External Grant Support – Funded projects Chromosome segregation during meiosis I in Drosophila females Principal Investigator: Kim S. McKim Award Period: 09/28/07 – 8/31/011 Agency: NIH 2 R01GM067142-05 Direct costs: $800,000 Total Costs: $1,212,984 “Crossover formation during meiosis in Drosophila females” Principal Investigator: Kim S. McKim Award Period: 10/01/07 – 09/30/10 Agency: NSF MCB-0719010 Direct costs: $323,630 Total Costs: $483,685




NAME

eRA COMMONS USER NAME (credential, e.g., agency login)

POSITION TITLE




Program Director/Principal Investigator (Last, First, Middle): McKinnon, Randall D.

Randall D. McKinnon, PhD Associate Professor

MCKINNON

Queens University, Kingston Canada BSc 1978 BiologyMcMaster University, Hamilton Canada PhD 1983 VirologyScripps Research Institute, La Jolla CA Postdoc. 1987 Mol. NeurobiologyUS National Institutes of Health, Bethesda MD Staff Fellow 1992 Glial Cell Biology

Please refer to the application instructions in order to complete sections A, B, and C of the Biographical Sketch.

A. Positions:1992-present: Assistant, Associate Professor of Surgery (Neurosurgery), RWJMS1998-present: Member, The Cancer Institute of New Jersey2005-present: Member, The Stem Cell Institute of New Jersey

B. Honors, Awards:1981: NCI Canada Studentship; McMaster U. Graduate Scholarship; H.L. Hooker Graduate Scholarship;Canadian National Science Engineering Scholarship. 1984, NCI Canada Postdoctoral Fellowship. 1988,U.S. National Multiple Sclerosis Society Sr. Fellowship. 1991,99, Instructor, Marine Biology Laboratory,Woods Hole MA. 1992, Reporter, International School of Neuroscience, Praglia Italy. 1994, Am SocNeurochem Annual Jordi Folch-Pi Memorial Award. 1995, Chair, ASN Symposia Organizer, LA CA. 1995,Chair, Neuroglia & Myelin, 25th Society Neuroscience, San Diego CA. 1996, First Award, NIH. 1998, Chair,Surgery Scholarship Workgroup; Chairs’ Appointee, Surg A&P Committee. 1998, Gallo Award, Cancer InstituteNew Jersey. 1998-02, Chair, RWJMS Distinguished Lecture Series, Molecular Biology in Medicine. 2001,National Science Teachers ExploraVision Award, 1st place, Pacific Rim. 2003, Member, Program Committee,ASN, Newport Beach CA. 2003, Symposia Chair, ASN Newport Beach CA. 2005, First Recipient in the US (1of 17), public (State) funds for Embryonic Stem Cell research. 2007, Soc. Neuroscience Public Education andCommunication Press Book, La Jolla CA. 2008, Chair, Int. Forum on Stem Cells, Tianjin China. 2009, InvitedSpeaker, Chinese Biopharm Assn, Guangzhou, China.

Federal Government and International Advisory Committees:1991, 1996-98, National Science Foundation. 1992, Neuro C Study Section, NIH. 1995-1997, NSPB StudySection, NIH. 1996, 2003, Multiple Sclerosis Society of Canada. 1997, 1999, The Welcome Trust, London UK.1998, 2003, The Cancer Institute of New Jersey. 1998-2003, Member, MCDN-6/ NCF Study Section, NIH.1999, Multiple Sclerosis Society of Great Britain. 2000-2007, Member, UMDNJ Foundation Grants Panel.2007, National U. Singapore Academic Research Fund. 2008, Medical Research Council of Great Britain.2009, ZRG1 Study Section, “Transformative RO1” Grants, NIH Bethesda. 2009, BDA-A Study Section, RC1hESC “Challenge” Grants, NIH. 2009, ETTN-A Study Section, Small Business: Developmental Biology andAging, NIH. 2009, MDCN-A 52R ZRG1 Study Section, AREA Grants, NIH.


Program Director/Principal Investigator (Last, First, Middle): McKinnon, Randall D.

C. Selected Peer Review Publications :

McKinnon, R.D., T. Matsui, M. Dubois-Dalcq and S.A. Aaronson (1990). FGF modulates the PDGF-drivenpathway of oligodendrocyte development. Neuron 5:603-14. (PMID: 2171589)

McKinnon, R.D., C. Smith, T. Behar, T. Smith and M. Dubois-Dalcq (1993). Distinct effects of bFGF andPDGF on O-2A progenitor cells. Glia 7: 245-254. (PMID: 8454310)

McKinnon,R.D., Piras,G., Ida,J. & Dubois-Dalcq,M. (1993). A role for TGF� in oligodendrocytedifferentiation. J. Cell Biology 6, 1397-1407. (PMID: 8509457)

McMorris, FA. and R.D.McKinnon (1996). Regulation of oligodendrocyte development and CNS myelination bygrowth factors: Prospects for therapy of demyelinating disease. Brain Pathology 6:313-29. (PMID: 8864287)

McKinnon, RD, G. Zazanis (1996) Transplantation of genetically engineered cells for analysis of gene functionin CNS development. METHODS: A Companion to Methods in Enzymology 10: 332-342. (PMID: 8954845).

Osterhout, D.J., S.Ebner, J.Xu, D.M.Ornitz, G.Zazanis, R.D.McKinnon (1997) Transplanted OL progenitorsexpressing a dom-negative FGFR transgene fail to migrate. J.Neurosci 17: 9122-32 (PMID: 9364059)

Ebner, S., M. Dunbar and R.D. McKinnon (2000). Distinct roles for PI3K in proliferation and survival ofoligodendroglial progenitor cells. J. Neuroscience Research 62: 336-345. (PMID: 11054802)

Yoshikawa, S. , R.D. McKinnon, M. Kokel and J.B. Thomas (2003) Wnt-mediated axon guidance throughthe Drosophila Derailed receptor. Nature 422: 583-588. (PMID: 12660735)

Labrador, J.P., D. O’Keefe, S .Yoshikawa, R.D. McKinnon, J.B. Thomas and G. Bashaw (2005). Thehomeobox transcription factor even-skipped regulates Netrin-receptor expression to control dorsalmotor-axon projections in Drosophila. Current Biology 15(15):1413-1419. (PMID: 16085495)

McKinnon, RD., S.Waldron, ME.Kiel (2005). PDGFR� signal strength controls an RTK rheostat that integratesPI3K and PLCg pathways during oligodendrocyte maturation. J. Neurosci. 25:3499-508. (PMID: 15814780).

Chen, C.P., M.E. Kiel, D. Sadowski and R.D. McKinnon (2007). From Stem Cells to Oligodendrocytes:Prospects for Brain Therapy. Stem Cell Reviews 3(4): 280-288. (PMID: 18060584)

Kiel, M.E., C.P. Chen, D. Sadowski and R.D. McKinnon (2008). Stem cell derived therapeutic myelinrepair requires 7% cell replacement. Stem Cells 26: 2229-36. (PMID: 18635868)

Sadowski, D., M.E. Kiel, M. Apicella, A.G. Arriola, CP Chen and R.D. McKinnon (2010). Teratogenic potentialin cultures optimized for OL development from mouse ESCs. Stem Cells and Development (in press).

Arriola, A.G., M.E. Kiel, Y. Shi and R.D. McKinnon (2010). Adjunctive MSCs enhance myelination by xeogenicoligodendrocytes transplanted in the retina. Cell Research, Nature Publishing Group (in press).

D. Research Support (last 3 years):RO1 MH54652, R.D.McKinnon (PI) 05/1997 - 04/2006, R.D.McKinnon (PI)

PDGF Signaling in Oligodendrocyte Development Direct costs: $1,125,000NJ Commission Spinal Cord Research, #05-3047-SCR-E-0 6/15/05 - 05/31/2007, R.D.McKinnon (PI)

Netrin directed glial migration Direct costs: $ 327,900NJ Commission, Stem Cell Research, # 06-2042-014-74 1/1/06 - 12/31/08, R.D.McKinnon (PI)

Gliogenic potential of human placental stem cells Direct costs: $ 260,868NJ Commission, Stem Cell Research 6/1/07 - 5/31/09, R.D.McKinnon (PI)

Stem cell therapeutics: PDGF-directed glial migration. Direct costs: $ 260,870NJ Commission, Stem Cell Research, CORE Facility Grant 10/1/2007 - 9/31/2010

Bioengineering of human embryonic stem cells. McKinnon, Roth, Pirrotta, Lu (Co-PIs)Core A: “Culture, gene transfer facility, R.D.McKinnon (PI) Direct costs: $ 633,389Core C: “Confocal imaging “, R.D.McKinnon (PI) Direct costs: $ 113,808Project 3: hESC derived oligodendrocytes, R.McKinnon (PI) Direct costs: $ 260,870



NAME Gaetano T. Montelione

eRA COMMONS USER NAME gaetano

POSITION TITLE Distinguished Professor II of Molecular Biology & Biochemistry



Cornell University, Ithaca, NY B.S. 1980 Biochemistry Cornell University, Ithaca, NY M.A. 1983 Physical Chemistry ETH, Zürich, Switzerland 1985-86 Biophysics Cornell University, Ithaca, NY Ph.D. 1987 Physical Chemistry Univ. of Michigan, Ann Arbor, MI Postdoc 1987 - 88 Molecular Biophysics

A. Personal Statement As director of the NIH-funded Northeast Structural Genomics Consortium of the NIGMS Protein Structure Initiative, Dr. Montelione leads an inter-institutional project in large-scale structural proteomics and bioinformatics. Goals of our work involve developing high-throughput technologies suitable for determining many new protein structures from the human genome project using bioinformatics, nuclear magnetic resonance spectroscopy (NMR) and X-ray crystallography. These structures provide important insights into the functions of novel gene products identified by genomic and/or bioinformatic analysis. The resulting knowledge of structure and biochemical function provides the basis for collaborations with academic laboratories and pharmaceutical companies to develop drugs useful in treating human diseases that are targeted to these newly discovered functions. The success of our approach relies on our abilities to identify, clone, express and analyze several hundred biologically interesting proteins per year; only a fraction of the initial sequences chosen for cloning and analysis result in high-resolution 3D structures. However, this “funnel” process is yielding three-dimensional structures and new functions for some 200 proteins per year, and can thus have tremendous scientific impact. Hypothesis-driven research areas enabled by this infrastructure and collaborations with other biologists include studies of protein complexes involved in influenza virus infection, innate immune response, networks of proteins associated with human cancer biology, and ubiquitination pathways. B. Positions and Honors Professional Experience and Service: 1988 – 1989 Research Assistant Professor, University of Michigan 1989-present Resident Faculty, Center for Advanced Biotechnology and Medicine 1989 Assistant Professor, Rutgers University 1992 - 1998 Executive Committee, Experimental NMR Conference (ENC) 1994 - 1998 Member, NSF Study Panel in Molecular Biophysics 1995 Associate Professor, Rutgers University 1998 - 2005 Professor, Rutgers University 1999 - 2003 Scientific Advisory Board, NMR Facility at Madison (NMRFAM) 2000-present Director, Northeast Structural Genomics Consortium 2000-present Associate Editor, Editorial Board Member, Proteins: Structure, Function, and Bioinformatics 2000-present Associate Editor, J. Struct. and Funct. Genomics 2001-present Adjunct Professor, Department of Biochemistry, University of Medicine and Dentistry of New

Jersey-Robert Wood Johnson Medical School (RWJMS) 2005-present Distinguished Professor II, Rutgers University 2005-present NMR Advisory Task Force for Protein Data Bank 2007-present Scientific Advisory Board, World-Wide Protein Data Bank (WW-PDB) 2008-present Scientific Advisory Board, BioMagResDatabase

Honors and Awards: 1981 - 1984 National Science Foundation Graduate Research Fellowship 1981 - 1982 Sage Research Fellowship, Cornell University 1987 Outstanding Chemistry Graduate Student, Cornell University 1988 - 1989 Damon Runyon-Walter Winchell Cancer Research Fellow 1989 - 1992 Searle Scholar Award 1990 - 1992 Johnson & Johnson Research Discovery Award 1992 - 1995 American Cyanamid Award in Physical and Analytical Chemistry 1993 - 1998 National Science Foundation Young Investigator Award 1994 - 1997 Proctor and Gamble Young Investigator Award 1995 Camille Dreyfus Teacher-Scholar Award 1995 Rutgers University Board of Trustees Award for Scholarly Excellence 1999 Biophysical Society Michael and Kate Bárány Award for Young Investigators 2006 Elected Fellow of the American Association for the Advancement of Science (AAAS) C. Selected Peer-reviewed Publications - Dr. Montelione is co-author of over 220 publications including: Qian, X.-Y.; Chien, C.-Y.; Lu, Y.; Montelione, G.T.; Krug, R.M. RNA 1995, 1: 948 - 956. An amino-terminal

polypeptide fragment of the influenza virus NS1 protein possesses specific RNA-binding activity and largely helical backbone structure.

Chien, C.-Y.; Tejero, R.; Huang, Y.; Zimmerman, D.; Krug, R.M.; Montelione, G.T. Nature Struct. Biol. 1997, 4: 891 - 895. A novel RNA-binding motif in influenza A virus non-structural protein 1.

Montelione, G.T; Anderson, S. Nature Struct. Biol. 1999, 6: 11 - 12. Structural Genomics: Keystone for a human proteome project.

Montelione, G.T.; Zheng, D.; Huang, Y.J.; Gunsalus, K.C; Szyperski, T. Nature Struct. Biol. 2000, 7: 982 - 985. Protein NMR spectroscopy in structural genomics.

Yuan, E.; Aramini, J.M.; Montelione, G.T.; Krug, R. M. Virology 2003, 304: 291 - 301. Structural Basis for ubiquitin-like ISG 15 protein binding to the NS1 protein of Influenza B virus: A protein–protein interaction function that is not shared by the corresponding N-terminal domain of the NS1 protein of Influenza A virus.

Chien, C.-Y.; Xu, Y.; Xiao, R.; Aramini, J.M.; Sahasrabudhe, P.V.; Krug, R.M.; Montelione, G.T. Biochemistry 2004, 43: 1950 - 1962. Biophysical characterization of the complex between double-stranded RNA and the N-terminal domain of the NS1 protein from Influenza A virus: Evidence for a novel RNA-binding mode.

Qing, G; Ma, L.; Khorchid, A; Swapna, G. V. T. ; Mal, T.K.; Takayama, M.M.; Xia, B.; Sangita Phadtare, S.; Ke, H.; Acton, T.; Montelione, G.T.; Ikura, M.; Inouye, M. Nature Biotechnology 2004, 22: 877 - 882. Conversion of E. coli to a protein-producing machinery by cold-shock expression vectors.

Huang, Y.J.; Montelione, G.T. Nature. 2005, 438: 36 - 37. News & Views: Proteins flex to function. Yin, C.; Khan, J.A.; Swapna, G.V.T.; Krug, R.M.; Tong, L.; Montelione, G.T. J. Biol. Chem. 2007, 282: 20584

-20592. Conserved surface features form the double-stranded RNA-binding site of non-structural protein 1 (NS1) from Influenza A and B viruses.

Liu, J.; Montelione, G. T.; Rost, B. Nature Biotechnology 2007, 25: 845 - 851. Novel leverage of structural genomics.

Aramini, J. M.; Rossi, P.; Anklin, C.; Xiao, R.; Montelione, G.T. Nature Methods 2007, 4: 491 - 493. Microgram scale protein structure determination by NMR.

Structural Genomics Consortium et al. Nature Methods 2008, 5: 135 - 146. Protein production and purification.

Das, K.; Ma, L-C.; Xiao, R.; Radvansky, B.; Aramini, J.; Zhao, L.; Marklund, J.; Kuo, R-L.; Twu, K.Y.; Arnold, E.; Krug, R.M.; Montelione, G.T. Proc. Natl. Acad. Sci. U.S.A. 2008, 105: 13092 - 13097. Structural basis for suppression by influenza A virus of a host antiviral response. PMCID: PMC2522260

Price, W.N.; Chen, Y.; Handelman, S.K.; …, A.; DeTitta, G.T.; Rost, B.; Montelione, G.T.; Hunt, J.F. Nature Biotechnology 2009, 27: 51 - 57. Understanding the physical properties that control protein crystallization by analysis of large-scale experimental data. PMCID: PMC2746436

Raman, S.; Lange, O.F.; Rossi, P.; Tyka, M.; Wang, X.; Prestegard, J.; Montelione, G.T.; Baker, D. Science 2010 (in press) NMR structure determination for larger proteins using backbone-only data.

D. Current Support 1 U54 GM074958 G.T. Montelione, P.I. 07/01/05 – 06/30/10 National Institutes of Health Center Grant “Structural Genomics of Eukaryotic Domain Families” The major goal of this project is to develop new technologies for structural genomics, and to apply them in determining ~1000 new protein domain structures from eukaryotic domain families, and to proteins involved in human cancer. The project involves both NMR and Xray crystallography, and supports over 100 researchers in 10 institutions that constitute the Northeast Structural Genomics Consortium.

P30CA072720C W. Hait, PI; G.T. Montelione, et al. coPIs 03/01/05 – 02/28/10 Cancer Institute of New Jersey (CINJ) “CINJ Protein Production and Structural Genomics Project” The major goal of this project is to conduct preliminary studies in Protein Production and Structure Analysis for researchers at the Cancer Institute of New Jersey.

U54 GM75026-01 Wayne A. Hendrickson, PI,; G. T. Montelione, et al coPIs 07/01/05 – 06/30/10 National Institutes of General Medical Science, National Institutes of Health “Structural Genomics of Membrane Proteins” Subcontract from NYSBC – Columbia University A component of a larger project focusing on NMR of membrane proteins and the development of new technologies for the production and isotope-enrichment of membrane proteins.

1 U01 AI074497 R. Krug, PI; G. T. Montelione, coPI 08/17/07 – 07/31/12 NIH/NIAID “Targeting the NS1 Protein for the Development of Influenza Virus Antivirals” The aim of this project is to utilize structural biology, molecular biology, virology, small molecule screening, and chemical synthesis to identify and optimize inhibitors of the H5N1 avian flu virus, as well as other strains of influenza virus.



NAME Bryce Nickels eRA COMMONS USER NAME (credential, e.g., agency login) BNICKELS

POSITION TITLE Assistant Professor of Genetics



Miami University B.S. 1991-1995 Chemistry Harvard University Ph.D 1996-2002 Microbiology Harvard University Post-doc 2002-2007 Microbiology

Please refer to the application instructions in order to complete sections A, B, and C of the Biographical Sketch. A. Positions and Honors Positions and Employment 1995-1996 Research Chemist Monsanto Co., St. Louis, MO 2002-2007 Postdoctoral Research Fellow with Dr. Ann Hochschild,

Department of Microbiology and Molecular Genetics, Harvard Medical School Boston, MA

2007-present Assistant Professor, Waksman Institute of Microbiology and Department of Genetics

Rutgers University, Piscataway, NJ Honors 1995 Phi Beta Kappa 2002 Molecular Microbiology Poster Prize

Molecular Genetics of Bacteria and Phages Meeting. Cold Spring Harbor, NY 2002 Nestlé Award

Journal of Bacteriology

2003 Bernard N. Fields Prize in Microbiology and Molecular Genetics Harvard Medical School, Boston, MA 2008 Pew Scholars Award

B. Publications 1. Milne JC, Roy RS, Eliot AC, Kelleher NL, Wokhlu A, Nickels B, and Walsh CT. Cofactor requirements and reconstitution of microcin B17 synthetase: a multienzyme complex that catalyzes the formation of oxazoles and thiazoles in the antibiotic microcin B17. Biochemistry (1999) 38, 4768-4781. 2. Kuznedelov K, Minakhin L, Niedziela-Majka A, Dove SL, Rogulja D, Nickels BE, Hochschild A, Heyduk T, and Severinov K. A role for interaction of the RNA polymerase flap domain with the σ subunit in promoter recognition. Science (2002) 295, 855-857. 3. Pande S, Makela A, Dove SL, Nickels BE, Hochschild A, and Hinton DM. The bacteriophage T4 transcription activator MotA interacts with the far C-terminal region of the σ70 subunit of Escherichia coli RNA polymerase. J. Bacteriol. (2002) 184, 3957-3964. 4. Nickels BE, Roberts CW, Sun H, Roberts JW, and Hochschild A. The σ70 subunit of RNA polymerase is contacted by the λQ antiterminator during early elongation. Mol. Cell (2002) 10, 611-622. 5. Nickels BE, Dove SL, Murakami KS, Darst SA, and Hochschild A. Protein-protein and protein-DNA interactions of σ70 region 4 involved in transcription activation by λcI. J. Mol. Biol. (2002) 324, 17-34. 6. Jain D, Nickels BE, Sun L, Hochschild A, and Darst SA. Structure of a Ternary Transcription Activation Complex. Mol. Cell (2004) 13, 45-53. 7. Gregory BD, Nickels BE, Garrity SJ, Severinova E, Minakhin L, Bieber Urbauer RJ, Urbauer JL, Heyduk T, Severinov K, and Hochschild A. A regulator that inhibits transcription by targeting an inter-subunit interaction of the RNA polymerase holoenzyme. Proc. Natl. Acad. Sci. U.S.A. (2004) 101, 4554-4559. 8. Nickels BE, Mukhopadhyay J, Garrity SJ, Ebright RH, and Hochschild A. The σ70 subunit of RNA polymerase mediates a promoter-proximal pause at the lac promoter. Nat. Struct. Mol. Biol. (2004) 11, 544-550. 9. Nickels BE and Hochschild A. Regulation of RNA Polymerase through the Secondary Channel. Cell (2004) 118, 281-284. 10. Gregory BD, Nickels BE, Darst SA, and Hochschild A. An altered-specificity DNA-binding mutant of Escherichia coli σ70 facilitates the analysis of σ70 function in vivo. Mol. Microbiol. (2005) 56, 1208-1219. 11. Nickels BE, Garrity SJ, Mekler V, Minakhin L, Severinov K, Ebright RH, and Hochschild A. The interaction between σ70 and the β-flap of Escherichia coli RNA polymerase inhibits extension of nascent RNA during early elongation. Proc. Natl. Acad. Sci. U.S.A. (2005) 102, 4488-93. 12. Deaconescu AM, Chambers AL, Smith AJ, Nickels BE, Hochschild A, Savery NJ and Darst SA. Structural Basis for Bacterial Transcription-Coupled DNA Repair. Cell (2006) 124, 507-520. 13. Nickels BE, Roberts CW, Roberts JW and Hochschild A. RNA-mediated destabilization of the σ70 region 4/β flap interaction facilitates engagement of RNA polymerase holoenzyme by the Q antiterminator. Mol. Cell (2006) 24, 457-468. 14. Deighan P, Montero Diez C, Leibman M, Hochschild A and Nickels BE. The bacteriophage λ Q antiterminator protein contacts the β flap domain of RNA polymerase. Proc. Natl. Acad. Sci. U.S.A. (2008) 105, 15305-15310.

15. Nickels BE. Genetic assays to define and characterize protein-protein interactions involved in gene regulation. Methods (2009) 47, 53-62. 16. Yuan AH, Nickels BE, and Hochschild A. The bacteriophage T4 AsiA protein contacts the β flap domain of RNA polymerase. Proc. Natl. Acad. Sci. U.S.A., (2009) 106, 6597-6602. 17. Goldman SR, Ebright RH, and Nickels BE. Direct detection of abortive RNA transcripts in vivo. Science (2009) 324, 927-928. 18. Stallings CL, Stephanou NC, Chu L, Hochschild A, Nickels BE and Glickman MS. CarD is an Essential Regulator of rRNA Transcription Required for Mycobacterium tuberculosis Persistence. Cell (2009) 138, 146-159. 19. Nickels BE. A new twist on a classic paradigm: illumination of a "genetic switch" in Vibrio cholerae phage CTXΦ. J. Bacteriol. (2009) 191, 6779-6781. 20. Devi G, Campbell EA, Darst SA, Nickels BE. Utilization of variably spaced promoter-like elements by the bacterial RNA polymerase holoenzyme during early elongation. Mol. Micro. (2010) in press. C. Research Support Pew Scholars Award 7/1/08-6/30/12 Pew Charitable Trust The goal of this project is to study the mechanism of transcription and its regulation in E. coli. Role: PI

1

Biographical Sketch Principal Investigator: Robert A. Niederman (i) Professional Preparation:

University of Connecticut, Storrs, Microbiology, B.S., 1959 University of Connecticut, Storrs, Microbiology, M.S., 1961 University of Illinois, Urbana, Veterinary Medicine, D.V.M., 1964 University of Illinois, Urbana, Microbiology, Ph.D., 1967 AEC Postdoctoral Fellow, Michigan State University, Biochemistry, 1967-68 Postdoctoral Fellow, Roche Institute of Molecular Biology, Physiological Chemistry, 1968-1970

(ii) Appointments: Professor, Dept. of Molecular Biology & Biochemistry, 7/80- and Vice Chair 7/89-6/94, Rutgers University, New Brunswick, NJ. Assistant Professor to Associate Professor, Dept. of Microbiology, 9/70-7/80, Rutgers Univ-ersity, New Brunswick, NJ. Visiting Professor, Dept. of Molecular Biology & Biotechnology, ’92, Univ. of Sheffield, UK. Research Fellow in Biochemistry, Dept. of Biochemistry, ‘77-’78, University of Bristol, UK.

(iii) Publications: Related to Proposed Project: (Five closely related publications -- out of 98) Woronowicz, K. and Niederman R.A. (2010) Proteomic analysis of the developing intracyto-

plasmic membrane in Rhodobacter sphaeroides during adaptation to low light intensity. In P.C. Hallenbeck (ed.) Recent Advances in Phototrophic Prokaryotes. Springer. New York, NY (In press).

Sturgis, J.N., Tucker, J.D., Olsen, J.D., Hunter, C.N., and Niederman, R.A. (2009) Atomic force microscopy studies of native photosynthetic membranes. Current Topics Review. Biochem-istry 48:3679-3698 (Among ten most-accessed Biochemistry articles during April-June 2009).

Koblízek, M., Shih, J.D., Breitbart, S.I., Ratcliffe, E.C., Kolber, Z.S., Hunter, C.N. and Niederman, R.A. (2005) Sequential assembly of photosynthetic units in Rhodobacter sphaeroides as revealed by fast repetition rate analysis of variable bacteriochlorophyll a fluorescence. Biochim. Biophys. Acta 1706:220-231.

Frese, R.N. Siebert, C.A., Niederman, R.A., Hunter, C. N., Otto, C. and van Grondelle, R. (2004) The long-range organization of a native photosynthetic membrane. Proc. Natl. Acad. Sci. USA 101:17994-17999.

Bahatyrova, S., Frese, R.N., Siebert, C.A., van der Werf, K.O., van Grondelle, R., Niederman, R.A., Bullough, P.A., Otto, C. Olsen, J.D. and Hunter, C.N. (2004) The native architecture of a photosynthetic membrane. Nature 430:1058-1062.

Other Significant Publications: Sturgis, J.N. and Niederman, R.A. (2008) Organization and assembly of light-harvesting

complexes in the purple bacterial membrane. In C.N. Hunter, F. Daldal, M.C. Thurnauer, and J.T. Beatty (eds), The Purple Phototrophic Bacteria. Advances in Photosynthesis and Respiration, Vol. 28, pp. 253-273, Springer, Dordrecht, The Netherlands

2

Georgakopoulou, S., van der Zwan, G., Olsen, J.D., Niederman, R.A., Hunter, C.N. and van Grondelle, R. (2006) Investigation of the effects of different carotenoids on the absorption and CD signals of LH1 complexes. J. Phys. Chem. B 110:3354-3361.

Westerhuis, W.H.J., Sturgis, J.N., Radcliffe, E.C., Hunter, C.N. and Niederman, R.A. (2002) Isolation, size estimates and spectral heterogeneity of an oligomeric series of light-harvesting 1 complexes from Rhodobacter sphaeroides. Biochemistry 41, 8698-8707.

Gradinaru, C.C., Kennis, J.T.M., Papagiannakis, E., van Stokkum, I.H.M., Cogdell, R.J., Fleming, G.R., Niederman, R.A. and van Grondelle, R. (2001) An unusual pathway of excitation energy deactivation in carotenoids: singlet-to-triplet conversion on an ultrafast time scale in a photosynthetic antenna. Proc. Natl. Acad. Sci. USA 98, 2364-2369.

Kolber, Z.S., van Dover, C.L., Niederman, R.A. and Falkowski, P.G. (2000) Bacterial photosynthesis in surface waters of the open ocean. Nature 407, 177-179.

(iv) Synergistic Activities:

1. Reviewer, Biosciences Panel, DOE Early Career Basic Energy Sciences Research Program, December 2009.

2. Co-Organizer, Satellite Workshop: Photosynthetic Light-Harvesting Systems, A Satellite Meeting of the 14th International Congress on Photosynthesis, Glasgow, UK, July, 2007.

3. Guest Editor, Photosynthesis Research, Special issue on photosynthetic antenna pigments and complexes, 2004-2005

4. Organizer, PS 2004 Light-Harvesting Systems Workshop: 13th International Congress on Photosynthesis/Montreal, CD, August 2004

5. Member, Chemistry and Related Sciences Special Emphasis Panel, NIH, 1996 6. Chair, Eastern Regional Photosynthesis Meeting, 1991 7. Member of Editorial Board of Journal of Bacteriology, 1983-1988

(v) Collaborators and Other Affiliations

(a) Collaborators Prof. Robert E. Blankenship. Washington University, St. Louis MO Prof. Harry A. Frank, University of Connecticut, Storrs CT Prof. C. Neil Hunter, Sheffield University, UK Dr. MichalKoblízek, Institute of Microbiology, Trebon, Czech Republic Dr. Zbigniew S. Kolber, Monterey Bay Aquarium Research Institute, Moss Landing, CA Prof. James N. Sturgis, Institute of Structural Biology and Microbiology, CNRS, Marseilles, France Prof. Rienk van Grondelle, Free University, Amsterdam, The Netherlands

(b) Graduate and Postdoctoral Advisors Prof. Meyer J. Wolin, University of Illinois, Urbana IL, Graduate Advisor, ‘64-’67 Prof. Willis A. Wood, Michigan State University, East Lansing MI, Postdoctoral Advisor, ‘67-’68 Dr. Kenneth D. Gibson, Roche Institute of Molecular Biology, Nutley NJ, Postdoctoral Advisor, ‘68-’70

(c) Thesis Advisor and Postgraduate-Scholar Sponsor Total number of graduate students advised: 17 Total number of postdoctoral scholars sponsored: 12

Current and Pending Support

Robert A. Niederman

Current Support Title: Structural and Functional Proteomic Analysis of a Developing Energy Transduc-

ing Membrane PI: Robert A. Niederman Agency: DOE grant Grant No. DE-FG02-08ER15957 from the Chemical Sciences, Geo-

sciences and Biosciences Division, Office of Basic Energy Sciences, Office of Science.

Amount: $565,000 (total costs)(3 person-months/yr) Duration: 6/15/08-6/14/11 Title: Byrne Undergraduate Seminar and Aresty Undergraduate Research Funds Agency: Rutgers University Amount: $4,500 (total costs)(1 person-months/yr) Duration: 07/01/09-6/30/10 Pending Support Title: Functional Interfacing of Photosynthetic Systems to Conducting Supports for

Capture and Conversion of Solar Energy PI: Robert A. Niederman Agency: NSF Amount: $834,690 (total costs)(3 person-month/yr) Duration: 04/01/10-3/31/13 This proposal: Title: Assembly of photosynthetic light-harvesting complexes in whole cells: A time-

resolved fluorescence spectroscopic study PI: Neal W. Woodbury, Su Lin, Arizona State University Subaward PI: Robert A. Niederman, Rutgers University Agency DOE Amount $46,300 (total costs)(1 person-month/yr) Duration: 05/01/10-4/30/13



NAME Padgett, Richard W. eRA COMMONS USER NAME padgett77

POSITION TITLE Professor, Molecular Biology and Biochemistry



University of North Carolina-Chapel Hill B.S. Honors 1977 Biology University of North Carolina-Chapel Hill Ph.D. 1985 Molecular genetics Harvard University Postdoc 1985-1990 Developmental genetics

Please refer to the application instructions in order to complete sections A, B, and C of the Biographical Sketch. A. Positions and Honors. Positions and Training 1977-1979 University of North Carolina, Research Technician in the Pathology. 1979-1985 University of North Carolina, graduate student in the Curriculum of Genetics with Drs. Clyde Hutchison III and Marshall Edgell, Ph.D., 1985. 1988 Max Planck Institute for Developmental Biology, Tübingen, Germany, participant in the EMBO Laboratory Workshop, "Drosophila Embryogenesis". 1985-1990 Harvard University, postdoctoral fellow in the Department of Cellular and Developmental Biology with Dr. William Gelbart. 1991-1996 Assistant Professor, Waksman Institute and the Department of Molecular Biology and

Biochemistry. 1996-2001 Associate Professor, Waksman Institute and the Department of Molecular Biology and

Biochemistry. 1999-present Director, Graduate Program in Cell and Developmental Biology. 2001-present Professor, Waksman Institute and the Department of Molecular Biology and Biochemistry. Fellowships and Academic Honors 1977 Graduated with Honors, Dept. of Zoology, UNC-Chapel Hill 1979-1980 UNC Graduate Student Scholarship Award 1980-1985 NIH Predoctoral Trainee in Genetics 1985-1988 NIH Postdoctoral Fellowship 1988-1990 Charles A. King Trust Postdoctoral Fellowship (Boston, MA) 1994-1998 Co-PI for a Howard Hughes Grant for Undergraduate Instruction, Rutgers University 1995 Outstanding Service, New Jersey Cancer Commission 1997-2000 NSF Eucaryotic Genetics Review Panel, member 1999-2001 NIH Biology I Panel, member 2006 Ad hoc member, Special Emphasis Panel NIH 2005-2009 NIH Dev2 study section, member B. Selected Publications and Invited Reviews (partial list): 1. Padgett, R.W., R.D. St. Johnston and W.M. Gelbart (1987). A Transcript from a Drosophila Pattern

Gene Predicts a Protein Homologous to the Transforming Growth Factor-β Family. Nature 325: 81-84.

2. St. Johnston, R. Daniel, F. Michael Hoffmann, Ronald K. Blackman, Daniel Segal, Raymond Grimaila, Richard W. Padgett, Holly Irick and William M. Gelbart (1990). The Molecular Organization of the decapentaplegic Gene in Drosophila melanogaster. Genes and Devel. 4:1114-1127.

3. Padgett, R.W. (1993). The Fly According to Lawrence. BioScience 43:251-252. 4. Hursh, D.A., R. W. Padgett and W. M. Gelbart (1993). Cross Regulation of decapentaplegic and

Ultrabithorax transcription in Embryonic Visceral Mesoderm Mediates Gut Morphogenesis in Drosophila, Development 117:1211-1222.

5. Padgett, R.W., J. Wozney and W.M. Gelbart (1993). Human BMP Sequences Can Confer Normal Dorsal-Ventral Pattering in the Drosophila Embryo, Proc. Natl. Acad. Sci. USA 90:2905-2909.

6. Finelli, A.L., C. A. Bossie, T. Xie and R. W. Padgett (1994). Antimorphic Alleles of the Drosophila tolloid Gene Contain Amino Acid Substitutions in the Protease Domain, Development 120: 861-870.

7. Xie, T., A.L. Finelli, and R.W. Padgett (1994). The Drosophila saxophone Gene: A Serine-Threonine Kinase Receptor of the TGF-β Superfamily, Science 263:1756-1759.

8. Finelli, A., T. Xie C. Bossie, R. Blackman, and R. W. Padgett (1995). The tolkin gene is a tolloid/BMP-1 Homologue that is Essential for Drosophila Development, Genetics 141: 271-281.

9. Twombly, V., R.K. Blackman, H. Jin, J.M. Graff, R.W. Padgett, and W.M. Gelbart (1996). The decapentaplegic signaling pathway is essential for Drosophila oogenesis, Development 125: 1555-1565.

10. Yingling, J.M., P.Das, C. Savage, M. Zhang, R.W. Padgett, and X-F. Wang (1996). Mammalian Dwarfins are Phosphorylated in Response to Transforming Growth Factor-β and Implicated in Control of Cell Growth, Inhibit Cell Growth and are Phosphorylated in Response to TGFβ Proc. Natl. Acad. Sci. USA 93: 8940-8944.

11. Kweon, K., Sturtevant, M.A., B. Biehs, V. Francois, R. W. Padgett, R. Blackman, and E. Bier (1996). The Drosophila decapentaplegic and short gastrulation and genes function antagonistically during adult wing vein development, Development 122: 4033-4044.

12. Derynck, R., W.M. Gelbart, R.M. Harland, C.-H. Heldin, S.E. Kern, J. Massagué, D.A. Melton, M. Mlodzik, R.W. Padgett, A.B. Roberts, J. Smith, G.H. Thomsen, B. Vogelstein, and X.-F. Wang (1996). Nomenclature: Vertebrate Mediators of TGFβ Family Signals, Cell 87:1996.

13. Savage, C., P. Das, A.L. Finelli, S.R. Townsend, C.Y. Sun, S. Baird, and R. W. Padgett (1996). The C. elegans sma-2, sma-3, and sma-4 Genes Define a Novel Conserved Family of TGFβ Pathway Components, Proc. Natl. Acad. Sci., USA 93:790-794.

14. Padgett, R.W., A.L. Finelli, C. Savage, T. Xie, and S.-H. Cho (1997). The tolloid-like Genes in Invertebrates, In: The Astacins-Structure and Function of a New Protein Family, R. Zwilling and W. Stocker, eds., Verlag DR. Kovac, Hamburg, Germany.

15. Newfeld, S.J., R.W. Padgett, S.D. Findley, B.G. Richter, M. de Cuevas, and W.M. Gelbart (1997). Molecular evolution at the decapentaplegic locus in Drosophila, Genetics 145:297-309.

16. Padgett, R.W., C. Savage, and P. Das (1997). Genetic and Biochemical Analysis of TGFβ Signal Transduction, Cyto. and Growth Factor Reviews 8: 1-9.

17. Maduzia, L., and R.W. Padgett (1997). Drosophila Mad, a member of the Smad family, translocates to the nucleus upon stimulation of the dpp pathway, Biochem. Biophys. Res. Comm. 238:595-598.

18. Padgett, R.W., P. Das, and S. Krishna (1998). TGFβ Signaling, Smads, and Tumor Suppressors, BioEssays 20:382-390.

19. Padgett, R.W., S-H. Cho, and C. Evangelista (1998). Smads are the central component in TGFβ signaling. Pharmacology and Therapeutics 78: 47-52.

20. Das, P., L. Maduzia, H. Wang, A. Finelli, S-H. Cho, M. Smith and R.W. Padgett (1998). The Drosophila gene Medea reveals the requirement for different classes of Smads in dpp signaling, Development 125: 1519-1528.

21. Colavita, A., S. Krishna, H. Zheng, R.W. Padgett and J.G. Colotti (1998). Pioneer Axon Guidance by UNC-129, a C. elegans TGFβ Science 281: 706-709.

22. Suzuki, Y., M.D. Yandell, P.J. Roy, M. Fleischmann, S. Krishna, C. Savage-Dunn, R.M. Ross, F. Mueller, R.W. Padgett, and W.B. Wood (1999) A C. elegans BMP2/4 Homolog Determines Body Size and Contributes to Male Tail Patterning, Development 126: 241-250.

23. Krishna, S. L.M. Maduzia, and R.W. Padgett (1999). Specificity of TGFβ signaling is imparted by distinct type I receptors and their associated SMAD proteins, Development 126: 251-260.

24. Das, P., H. Inoue, J.C. Baker, H. Beppu, M. Kawabata, R.M. Harland, K. Miyazono, and R.W. Padgett (1999). Drosophila dSmad2 and Atr-I transmit activin/TGFβ Signals, Genes to Cells 4: 123-134.

25. Padgett, R.W. (1999) TGFβ Signaling: New Insights from Receptor and Smad Studies, Current Biology 9:R408-R411.

26. Padgett, R. W. (1999). TGFβ Signaling Pathways and Disease, Cancer & Metastasis Reviews, 18:247-259.

27. Das, P., L.L. Maduzia, and R. W. Padgett (1999). INSIGHTS FROM MODEL SYSTEMS: Elucidating Signaling Pathways in C. elegans and Drosophila, Cyto. and Growth Factor Reviews, 10:179-186.

28. Patterson, G. I. and Padgett, R.W. (2000). TGFβ and C. elegans Development, Trends in Genetics, 16:27-33.

29. Savage-Dunn, C., R. Tokarz, H. Wang, S. Cohen, C. Giannikas, and R.W. Padgett (2000). sma-3 Smad has specific and critical functions in DBL-1/SMA-6 TGFβ-like signaling, Dev. Biol. 223:70-76.

30. Zimmerman, C. and R.W. Padgett (2000). TGFb Signaling Mediators and Modulators, Gene 249:17-30.

31. Padgett, R.W., and G.I. Patterson (2001). New Developments for TGFβ, Dev. Cell 1:343-349. 32. Gumienny, T., and R.W. Padgett (2002). Extracellular Mediators of TGFβ Signaling, Trends in

Endocrinology 13:295-299. 33. Maduzia, L. L., Gumienny, T. L., Zimmerman, C. M., Wang, H., Shetgiri, P., Krishna, S., Roberts, A. F. and

R.W. Padgett, (2002). lon-1 regulates Caenorhabditis elegans body size downstream of the dbl-1 TGFβ signaling pathway. Dev Biol 246, 418-428.

34. Gumienny TL, Padgett RW (2003). A small issue addressed. Bioessays 25(4):305-8. 35. Nelson DW, Padgett RW (2003). Insulin worms its way into the spotlight. Genes Dev 17(7):813-836. 36. Patton, J.R. and R.W. Padgett (2003). Caenorhabditis elegans Pseudouridine Synthase Activity in vivo:

tRNA is a Substrate but not U2 Small Nuclear RNA, Biochem. Journal 372(Pt 2):595-602. 37. Savage-Dunn, C., Maduzia, L. L., Zimmerman, C. M., Roberts, A. F., Cohen, S., Tokarz, R. and R.W.

Padgett (2003). Genetic screen for small body size mutants in C. elegans reveals many TGFβ pathway components. Genesis 35, 239-247.

38. Yang M, Nelson D, Funakoshi Y, and R.W. Padgett (2004). Genome-wide microarray analysis of TGFβ signaling in the Drosophila brain. BMC Dev Biol 4(1):14.

39. Kirilly D, Spana EP, Perrimon N, Padgett RW, Xie T (2005) BMP signaling is required for controlling somatic stem cell self-renewal in the Drosophila ovary, Dev Cell 9(5):651-62.

40. Maduzia, L. L., Roberts, A. F., Wang, H., Lin, X., Chin, L. J., Zimmerman, C. M., Cohen, S., Feng, X. H. and R.W. Padgett, (2005). C. elegans serine-threonine kinase KIN-29 modulates TGFβ signaling and regulates body size formation. BMC Dev Biol 5(1):8.

41. Robins H., Li Y., and R.W. Padgett (2005). Incorporating structure to predict microRNA targets, Proc Natl Acad Sci U S A 102(11):4006-4009.

42. Yang M, Li Y, Padgett RW (2005). MicroRNAs: Small regulators with a big impact. Cytokine Growth Factor Rev 16(4-5):387-393.

43. Goff, L. A., M. Yang, J. Bowers, R. C. Getts, R. W. Padgett, and R. P. Hart (2005). Rational probe optimization and enhanced detection strategy for microRNAs using microarrays, RNA Biology, 2:3 e9-e16.

44. Patton, J.R., and R. W. Padgett (2005). Pseudouridine modification in Caenorhabditis elegans spliceosomal snRNAs: unique modifications are found in regions involved in snRNA-snRNA interactions, BMC Molecular Biology, 6:20.

44. Yu, B., Z. Yang, J. Li, S. Minakhina, M.Wang, R.W. Padgett, R. Steward, and X. Chen (2005). Methlyation as Crucial Step in Plant microRNA Biogenesis, Science 307:932-935.

45. Ibáñez-Ventoso, C., M. Yang, S. Guo, H. Robins, R.W. Padgett, and M. Driscoll (2006). Modulated microRNA expression during adult lifespan in C. elegans, Aging Cell, 5(3):235-246.

46. Gumienny, T.L., L.T. MacNeil, H. Wang, J.L. Wrana, and R.W. Padgett (2007). Glypican LON-2 is a negative regulator of BMP-like signaling in Caenorhabditis elegans, Current Biology, 17(2):159-164.

47. Padgett, R.W. and G.I. Patterson (2007). C. elegans TGFβ Signaling Pathways, Eds. R. Derynck and K. Miyazono, Cold Spring Harbor Press, in press.

48. Patterson, G.I. and R.W. Patterson (2007) TGFβ Signaling in C. elegans, Eds. C. Heldin and P. ten Dijke, Springer Science, in press.

49. Padgett, R.W. and M. Reiss (2007) TGFβ superfamily signaling: notes from the desert, Development 134:3565-3569.

50. Yang, M., J.E. Lee, R.W. Padgett and I. Edery (2008). Circadian regulation of a limited set of microRNAs in Drosophila, BMC Genomics, 9:83.

51. Gumienny, T.L., L. MacNeil, C. Zimmerman, H. Wang, L. Chin, J. Wrana, and R.W. Padgett (2009). C. elegans SMA-10 is a conserved transmembrane protein that is required for TGFβ superfamily signaling, submitted to PLoS Genetics, in revision.

52. Roberts, A.F., T.L. Gumienny, R.J. Gleason, H. Wang, and R.W. Padgett (2009). Regulation of genes affecting body size and innate immunity by the DBL-1/BMP pathway in Caenorhabditis elegans, in revision.

C. RESEARCH SUPPORT Ongoing Research Support NSF Richard W. Padgett (PI) 8/1/07-7/31/10 NSF/Developmental Biology Growth Control by TGFβ in Drosophila This project studies an activin-like ligand and three downstream target genes of TGFβ in Drosophila. Role: PI R01 CA129125 Michael Reiss (PI) 07/01/2007-6/30/2012 Targeting TGFβ receptor mutations in cancer and other diseases NIH/CA This project studies TGFβ receptor mutations as they relate to cancers and Marfan’s syndrome. Our role is to use bioassays in Drosophila to test whether human receptor mutations are hypomorphs, hypermorphs, or neomorphs. Co-PI: Richard W. Padgett (we receive $25k in direct costs) Completed Research (within 3 years) CINJ Interdisciplinary Grant 12/2005-11/2007 Induction of miRNA genes during breast cancer progression (human studies) $105,000 direct Role: PI DOD Breast Cancer Program 8/2005-7/2007 Role of miRNA genes in breast cancer progression (mouse studies) $75,000 direct Role: PI NIH Richard W. Padgett (PI) 7/2001-6/2007 NIH/Child Health Institute Analysis of C. elegans TGFβ Signal Transduction $180,000 direct

Program Director/Principal Investigator (Last, First, Middle): Pestka, Sidney




NAME Pestka, Sidney eRA COMMONS USER NAME PESTKA

POSITION TITLE Professor & Chairman



Princeton University A.B. 1957 Chemistry University of Pennsylvania, Philadelphia, PA M.D. 1961 Medicine Baltimore City Hospital, Baltimore, MD Internship 1961-62 Pediatrics/Medicine

A. Positions and Honors: 1962-1966 Postdoctoral work with Dr. Marshall W. Nirenberg, NIH 1966-1969 National Cancer Institute, NIH, Independent Laboratory 1969-1986 Department of Biochemistry, Roche Institute of Molecular Biology 1972-date Adjunct Professor of Pathology, College of Physicians and Surgeons, Columbia University 1986-date Prof./Chair, Dept. of Molec. Gen., Microbio. & Immun., UMDNJ-RobertWoodJohnsonMedSchool Selected Awards: 1987, Honorary Doctor of Science, Rider Univ.; 1993, NJ Hall of Fame; 2001, Milstein Award, Society Interferon Cytokine Res; 2002, Fleet Award ; 2002, National Medal of Technology; 2004, Warren G. Alpert Prize, Harvard University; 2006, Lemelson-MIT Lifetime Achievement Award B. Selected Peer-Reviewed Publications or Manuscripts in Press Pestka, S. (1969) "Studies on the Formation of Transfer Ribonucleic Acid-Ribosome Complexes. VI.

“Oligopeptide Synthesis and Translocation on Ribosomes in the Presence and Absence of Soluble Transfer Factors," J. Biol. Chem. 244, 1533-1539.

Pestka, S., McInnes, J., Havell, E., and Vilček, J. (1975) "Cell-free Synthesis of Human Interferon," Proc. Natl. Acad. Sci. U.S.A. 72, 3898-390l. Langlois, R., Lee, C.C., Cantor, C.R., Vince, R., and Pestka, S. (1976) "The Distance Between Two

Functionally Significant Regions of the 50S Escherichia coli Ribosome: The Erythromycin Binding Site and Proteins L7/L12," J. Mol. Biol. 106, 297-313.

Rubinstein, M., Rubinstein, S., Familletti, P.C., Gross, M.S., Miller, R.S., Waldman, A.A. and Pestka, S. (1978) "Human Leukocyte Interferon Purified to Homogeneity," Science 202, 1289-1290.

Maeda, S., McCandliss, R., Gross, M., Sloma, A., Familletti, P.C., Tabor, J.M., Evinger, M., Levy, W.P., and Pestka, S. (1981) "Construction and Identification of Bacterial Plasmids Containing Nucleotide Sequence for Human Leukocyte Interferon," Proc. Natl. Acad. Sci. U.S.A. 77, 7010-70l3; 78, 4648.

Miller, D.L., Kung, H.-F., and Pestka, S. (1982) "Crystallization of Recombinant Human Leukocyte Interferon A," Science 215, 689-690.

Pestka, S., Daugherty, B.L., Jung, V., Hotta, K., and Pestka, R.K. (1984) "Anti-Messenger RNA: Specific Inhibition of Translation of Single mRNA Molecules," Proc. Natl. Acad. Sci. U.S.A. 81, 7525-7528.

Greiner, J.W., Guadagni, F., Noguchi, P., Pestka, S., Colcher, D., Fisher, P.B., Schlom, J. (1987) "Recombinant Interferon Enhances Monoclonal Antibody-Targeting of Carcinoma Lesions in Vivo," Science 235,895-898.

Soh, J., Donnelly, R.J., Mariano, T.M., Cook, J.R., Schwartz, B., and Pestka, S. (1993) "Identification of a Yeast Artificial Chromosome Clone Encoding an Accessory Factor for the Human Interferon Gamma Receptor: Evidence for Multiple Accessory Factors," Proc. Natl. Acad. Sci. U.S.A. 90, 8737-8741.

Soh, J., Donnelly, R.J., Kotenko, S., Mariano, T.M., Cook, J.R., Wang, N., Emanuel, S.L., Schwartz, B., Miki, T. and Pestka, S. (1994) "Identification and Sequence of an Accessory Factor Required for Activation of the Human Interferon Gamma Receptor," Cell 76, 793-802.

Kotenko, S.V., Krause, C.D., Izotova, L.S., Pollack, B.P., Wu, W., and Pestka, S. (1997) "Identification and Functional Characterization of a Second Chain of the Interleukin-10 Receptor Complex," EMBO J. 16, 5894-5903.

Program Director/Principal Investigator (Last, First, Middle): Pestka, Sidney


Livnah, O., Johnson, D.L., Stura, E.A., Farrell, F.X., Barbone, F.P., You, Y., Liu, K.D., Goldsmith, M.A., He, W., Krause, C., Pestka, S., Jolliffe, L.K., and Wilson, I.A. (1998) “An Antagonist Peptide - EPO Receptor Complex Suggests that Receptor Dimerization is not Sufficient for Activation,” Nat. Struct. Biol. 5, 993-1004.

Sarkar, S., Pollack, B.P., Lin, K-T., Kotenko, S.V., Cook, J.R., Lewis, A., and Pestka, S. (2001) “hTid-1, A Human DnaJ Protein Modulates the Interferon Signaling Pathway,” J. Biol. Chem. 276, 49034-49042.

Kotenko, S.V., Izotova, L.S., Mirochnitchenko, O.V., Esterova, E., and Pestka, S. (2001) “Identification, Cloning and Characterization of a Novel Soluble Receptor which Binds IL-22, and Neutralizes its Activity,” J. Immunol. 166, 7096-7103.

Krause, C. D., Mei, E., Xie, J., Jia, Y., Bopp, M. A., Hochstrasser, R. M., Pestka, S. (2002) “Seeing the Light: Preassembly and Ligand-Induced Changes of the Interferon Gamma Receptor Complex in Cells,” Molecular & Cellular Proteomics 1, 805-815.

Pestka, S. (2003) “A Dance between Interferon-α/β and p53 Demonstrate Collaborations in Tumor Suppression and Antiviral Activities,” Cancer Cell 4, 85-87.

Brewer, G., Saccani, S., Sarkar, S., Lewis, A., and Pestka, S. (2003) “Increased Interleukin-10 mRNA Stability in Melanoma Cells is Associated with Decreased Levels of A+U-Rich Element Binding Factor AUF1,” Journal of Interferon and Cytokine Research 23, 553-564.

Wu, W., Kerrigan, J.E., Yadav, P., Schwartz, B., Izotova, L., Lavoie, T.B., and Pestka, S. (2004) “Design and Construction of a Phosphoylatable Chimeric Monoclonal Antibody with a Highly Stable Phosphate,” Oncology Research/Incorporating Anti-Cancer Drug Design. 14, 541-558.

Krause, C.D. and Pestka, S. (2005) “Evolution of the class 2 cytokines and receptors, and discovery of new friends and relatives,” Pharmacol. Ther. 106, 269-430.

Krause, C.D., Mei, E. Mirochnitchenko, O.V., Lavnikova, N., Xie, J., Jia, Y., Hochstrasser, R.M., and Pestka, S. (2005) “Interactions Among the Components of the Interleukin-10 Receptor Complex,” Biochem Biophys Res Commun, 340, 377-385.

Pestka, S. and Krause, K. (2006) “Interferon and Related Receptors,” Chapter 5 in The Interferons: Characterization and Application (A. Meager ed.), Wiley-VCH, 113-140 (in press).

Krause, C. D., Lavnikova. N., Xie, J., Mei, E., Mirochnitchenko, O.V., Jia, Y., Hochstrasser, R.M.and Pestka, S. (2006) “Preassembly and Ligand-Induced Restructuring of the Chains of the IFN-g Receptor Complex: The Roles of Jak Kinases, Stat1 and the Receptor Chains,” Cell Research, 16, 55-69.

Krause, C.D., He, W.,Kotenko, S., and Pestka, S. (2006) “Modulation of the Activation of Stat1 by the Interferon-gamma Receptor Complex, ” Cell Research, 16, 113-123.

Krause, C.D., Yang, Z-H., Kim, Y-S., Lee, J-H., Cook, J.R., and Pestka, S. (2007) “Protein arginine methyltransferases: Evolution and assessment of their pharmacological and therapeutic potential,” Pharmacology & Therapeutics, 113, 50-87.

Pestka, S. (2007) “The Interferons: 50 Years after Their Discovery There Is Much More to Learn,” J. Biol. Chem., 282, 20047-20051.

Sinsimer, K.S, Gratacós, F.M., Knapinska, A.M., Lu, J., Krause, C.D., Wierzbowski, A.V., Maher, L.R., Scrudato, S., Rivera, Y.M., Gupta, S., Turrin, D.K., de la Cruz, M.P., Pestka, S., and Brewer, G. (2008) Chaperone Hsp27, a novel subunit of AUF1 protein complexes, functions in AU-rich element-mediated mRNA decay. Mol. Cell. Biol., 28: 5223-5237.

Sarkar, S., Sinsimer, K.S., Foster R.L., Brewer, G., and Pestka, S. (2008) AUF1 Isoform-Specific Regulation of Anti-Inflammatory Cytokine IL10 Expression in Monocytes. J. Interferon Cytokine Res (in Press). C. Research Support: ONGOING

1 P01 AI057596-03 (Sidney Pestka, P.I.) 7/15/04 - 6/30/10 (ARRA funds) NIH - National Institute of Allergy and Infectious Diseases -- “Role of mRNA Decay in the Immune System”

How mRNA turnover controls various steps in immune activation 2 07-2042-014-88 (Sidney Pestka, P.I.) NJSCST Grant 09/01/07 – 01/31/10 (no cost extension) NJCST- -“Use of Stem Cells for Delivery of Biotherapeutics for the Treatment of Cancer”

To use the new alpha interferons with high antiproliferative activity to be delivered to tumors. 3. New Jersey Healthcare Foundation (Sidney Pestka, P.I.) 10/16/06-10/16/07 (no cost extension)

Treatment & Prevention of Cervical Dysplasia & Cancer Developef a treatment for cervical dysplasia caused by HPV & aid the prevention of cervical cancer.

Program Director/Principal Investigator (Last, First, Middle): Pintar, John E.


BIOGRAPHICAL SKETCH

NAME John Pintar eRA COMMONS USER NAME (credential, e.g., agency login) jpintar




Case Western Reserve University B.A. 1970 Biology, Chemistry University of Oregon Ph.D. 1977 Developmental Biology Yale University School of Medicine Post Doc 1978-81 Neurochemistry & Genetics

A. Positions and Honors Positions 1981-1983: Assistant Professor of Medicine and Anatomy, Mt. Sinai School of Medicine, New York 1983-1989: Assistant Professor of Anatomy and Cell Biology (in Center for Reproductive Science), Columbia

University, College of Physicians and Surgeons, New York 1990-1991: Associate Professor of Anatomy and Cell Biology (Center for Reproductive Science and the Center

for Neurobiology), Columbia University, College of Physicians and Surgeons, New York 1992-1995: Associate Professor of Neuroscience and Cell Biology, UMDNJ-Robert Wood Johnson Medical

School, Piscataway, NJ 1995-Present: Professor of Neuroscience and Cell Biology, UMDNJ-RWJMS, Piscataway, NJ Honors and Awards James Hudson Brown Postdoctoral Fellowship, 1979; Irma T. Hirschl Career Scientist Award, 1983; Charles Judson Herrick Award, 1985; Fulbright Senior Scholar, 1991. NIH Endocrine Study Section Special Reviewer, August 1988; NIH - Member, Growth Factors during Development, Ad Hoc Study Section, August 1988; NIH Extramural Site Visit Team, NIH Laboratory of Developmental Neurobiology, Nov. 1990; NIH Extramural Site Visit Team, NIDA Branch of Molecular Neurobiology, July 1997; NIH Ad Hoc reviewer, HED SS2, Nov. 1992 and Oct. 1993; Physiological Sciences, July 1994, Nov. 1994, July 1995, March 1997; HED2, Feb. 1996; ZRG2, July 1996; March 1997; NIDA-B, March 1998; MDCN-5, June 1998, Oct. 1998; Feb. June, Oct. 1999; Feb, June, Oct 2000; Feb, June, October, 2001; February, June, Oct. 2002; June, Oct, 2003, June, Oct. 2004; Oct., 2005; NINDS Pain PPG review, 5/05; 6/06; Extramural site visits, NIDA, Jan, 2000; Jan., 2001; Reviewer: Med. Res. Council, Canada; Med. Res. Council, Australia; Soc. Neuroscience, Education Committee: 2002-2005; NIDA translation training grant review; 6/06; MPNS study section 10/06-7/10. B. Selected Peer-Reviewed Publications (selected publications from 130): Mathon DS, Ramakers GM, Pintar JE, Marinelli M.Eur J Neurosci. 2005 Decreased firing frequency of midbrain

dopamine neurons in mice lacking mu opioid receptors May;21(10):2883-6. Benamar K, McMenamin M, Geller EB, Chung YG, Pintar JE, Adler MW. 2005. Unresponsiveness of mu-opioid

receptor knockout mice to lipopolysaccharide-induced fever Br J Pharmacol.;144(8):1029-31 Peinado JR, Laurent V, Lee SN, Peng BW, Pintar JE, Steiner DF, Lindberg I. (2005). Strain-dependent

Influences on the hypothalamo-pituitary-adrenal axis profoundly affect the 7B2 and PC2 null phenotypes. Endocrinology EPUB MAY 5.

Morgan DJ, Mzhavia N, Peng B, Pan H, Devi LA, Pintar JE. (2005). ProSAAS expression and processing during development. J. Neurochemistry 93(6):1454-62.

Czyzyk, TA., Ning Y., Hsu, M-S., Mains, R., Eipper, BA and Pintar, JE. (2005). Deletion of peptide amidation enzymatic activity leads to edema and embryonic lethality in the mouse, Developmental Biology, in press; epub 10/11.

Ning Y, Schuller AG, Bradshaw S, Rotwein P, Ludwig T, Frystyk J, Pintar JE. (2006).Diminished Growth and Enhanced Glucose Metabolism in triple knock out mice containing mutations of insulin like-growth factor

Program Director/Principal Investigator (Last, First, Middle): Pintar, John E.


binding proteins -3, -4, and -5.Mol Endocrinol. 2006 May 4; [Epub ahead of print] Ansonoff MA, Zhang J, Czyzyk T, Rothman RB, Stewart J, Xu H, Zjawiony J, Siebert DJ, Yan F, Roth BL,

Pintar JE. (2006). Antinociceptive and hypothermic effects of salvinorin A are abolished in a novel strain of KOR-1 KO mice. J Pharmacol Exp Ther. 2006 May 3.

Lee SN, Peng B, Desjardins R, Pintar JE, Day R, Lindberg I. (2007). Strain-specific steroidal control of pituitary function.J Endocrinol. 2007 Mar;192(3):515-25.

Murali SG, Liu X, Nelson DW, Hull AK, Grahn M, Clayton MK, Pintar JE, Ney DM (2007). The Intestinotrophic Effects of Exogenous Insulin-Like Growth Factor-I (IGF-I) Are Not Diminished in IGF Binding Protein-5 Knock-Out Mice. Am J Physiol Regul Integr Comp Physiol. 2007 Mar 1.

Petraschka M, Li S, Gilbert TL, Westenbroek RE, Bruchas MR, Schreiber S, Lowe J, Low MJ, Pintar JE, Chavkin C. (2007). The absence of endogenous beta-endorphin selectively blocks phosphorylation and desensitization of mu opioid receptors following partial sciatic nerve ligation. Neuroscience. 2007 Apr 27; [Epub ahead of print]

Ning Y, Hoang B, Schuller AG, Cominski TP, Hsu MS, Wood TL, Pintar JE. (2007). Delayed mammary gland involution in mice with mutation of the insulin-like growth factor binding protein 5 gene. Endocrinology. 2007 May; 148(5): 2138-47. Epub 2007 Jan 25.

Lofqvist C, Chen J, Connor KM, Smith AC, Aderman CM, Liu N, Pintar JE, Ludwig T, Hellstrom A, Smith LE. (2007). IGFBP3 suppresses retinopathy through suppression of oxygen-induced vessel loss and promotion of vascular regrowth. Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10589-94. Epub 2007 Jun 13.

Juni A, Klein G, Pintar JE, Kest B.(2007). Nociception increases during opioid infusion in opioid receptor triple knockout mice. Neuroscience. 2007 Jun 29;147(2):439-44. Epub 2007 Jun 1

Ning Y, Schuller AG, Conover CA, Pintar JE (2008). Insulin-like growth factor (IGF) binding protein-4 is both a positive and negative regulator of IGF activity in vivo. Mol Endocrinol.May;22(5):1213-25.Epub 2008 Feb 7. Giangreco A, Qin M,Pintar JE, Watt FM (2008). Epidermal stem cells are retained in vivo throughout skin

aging. Aging Cell. Mar;7(2):250-9. Epub 2008 Jan 21. Weber ML, Farooqui M, Nguyen J, Ansonoff M, Pintar JE, Hebbel RP, Gupta K. (2008) Morphine induces Mesangial cell proliferation and glomerulopathy via kappa-opioid receptors. Am J Physiol Renal Physiol. 2008 Jun;294(6):F1388-97. Epub 2008 Apr 2. Burmeister MA, Ansonoff MA, Pintar JE, Kapusta DR. (2008) Nociceptin/orphanin FQ (N/OFQ)-evoked

bradycardia, hypotension, and diuresis are absent in N/OFQ peptide (NOP) receptor knockout mice. J Pharmacol Exp Ther. 2008 Sep;326(3):897-904. Epub 2008 Jun 6.

Wen T, Peng B, Pintar JE. (2009) The MOR-1 opioid receptor regulates glucose homeostasis by modulating insulin secretion. Mol Endocrinol. 2009 Feb 12. [Epub ahead of print]. C. Research Support (research projects, last three years): Active:

NIH: T32: MH/AG19957 “Molecular and developmental basis of mental illness and aging”. J.E. Pintar, P.I. This is a multi-investigator training grant, with the long-term goal being to provide pre- and postdoctoral training in the above discipline, 09/30/96-06/30/09.

NIH: CA-053750 “Opioid receptor systems and breast cancer prevention.” 03/01/05-02/28/10; K. Gupta, P.I,, J.E. Pintar, Co-PI. NIH: MH-060706, “Neural and behavioral impact of T cell activation.” 1/11/06-12/31/10; A. Kusnecov, PI, J. E. Pintar, Co-PI NIH: DA004494 “Neuropeptides, processing enzymes, and drug abuse.” 09/1/06-03/31/11. L Fricker, P.I., J. E. Pintar, Co-PI.

Lilly Corporation Research grant ”Feeding behavior in opioid receptor knockout mice.” J.E. Pintar, P.I. 10/1/05-9/30/07; renewal until 11/30/09. R01 HL68802,”Opioid activity in endothelium in sickle cell disease.” 06/01/09-05/31/12, K. Gupta, P.I., J.E. Pintar, Co-PI.

New Jersey Commission on Brain Injury Research grant "Role of IGF binding proteins in response to brain injury." 06/01/09-05/31/11. J.E.Pintar, P.I.

NIH: 3R01DK042835, “Parenteral nutrition: intestinal metabolism/adaptation.” 09/01/09-08/31/10. D. Ney, P.I., J.E. Pintar, Co-PI.



NAME Christopher Rongo eRA COMMONS USER NAME chrisrongo

POSITION TITLE Associate Professor of Genetics



University of California San Diego B.A. 1987-1990 Molecular Biology Massachusetts Institute of Technology Ph.D. 1990-1996 Developmental Biology Mass. General Hospital/Harvard Med. School Postdoctoral 1996-1997 Neurobiology University of California Berkeley Postdoctoral 1997-2000 Neurobiology

A. Positions and Honors. Positions and Employment 1989-1990 Research Assistant, Laboratory of Dr. David Brenner, University of California San Diego School

of Medicine. 1991-1996 Doctoral Research, Laboratory of Dr. Ruth Lehmann, Department of Biology, Whitehead

Institute/Massachusetts Institute of Technology. 1996-1997 Postdoctoral Fellow, Massachusetts General Hospital Department of Molecular Biology/Harvard

Medical School Department of Genetics, Laboratory of Dr. Joshua Kaplan. 1997-2000 Postdoctoral Fellow, University of California Berkeley, Department of Molecular and Cell

Biology, Laboratory of Dr. Joshua Kaplan. 2000-2006 Assistant Professor, Waksman Institute/Rutgers University, Department of Genetics 2 006-present Associate Professor, Waksman Institute/Rutgers University, Department of Genetics Other Experience and Professional Memberships 1998-present Member, American Society for the Advancement of Science 2000-present Siemens Westinghouse Science & Technology Competition Judge 2001-present Member, Society for Neuroscience 2001-present Member, American Society for Cell Biology 2001 Molecular, Cellular and Developmental Neuroscience A Fellowship Review Panel, NIH. 2002 The Wellcome Trust Neurosciences Scientific Program Grant Review Panel. 2004 Molecular, Cellular and Developmental Neuroscience A Grant Review Panel, NIH. 2004-present Division of Integrative Biology and Neuroscience Grant Review Panel, NSF. 2005-present The Israel Science Foundation Grant Review Panel. 2005 Human Frontiers Science Program Grant Review Panel. 2008-2009 Molecular, Cellular and Developmental Neuroscience SEP (ZRG1 MDCN-N) Scientific Review

Group, Center for Scientific Review, National Institutes of Health. 2009-present Member, New York Academy of Sciences 2009-present Molecular, Cellular and Developmental Neuroscience IRG (SYN) Scientific Review Group,

Center for Scientific Review, National Institutes of Health. Honors 1990 Phi Beta Kappa, University of California San Diego 1990 National Science Foundation Graduate Fellowship 1997-2000 The Jane Coffin Childs Memorial Fund for Medical Research Postdoctoral Fellowship 2001-2005 Pew Scholar in the Biomedical Sciences

B

. Selected peer-reviewed publications (in chronological order). 7. Shim, J., Umemura, T., Nothstein, E., and Rongo, C. (2004) The Unfolded Protein Response regulates

lutamate receptor export from the endoplasmic reticulum. Molecular Biology of the Cell 15:4818-4828. g 8. Glodowski, D.R., Wright, T., Martinowich, K., Chang, H.C., Beach, D., and Rongo, C. (2005) Distinct LIN-10 domains are required for its neural function, its epithelial function, and its synaptic localization. Molecular

iology of the Cell: 16:1417-1426. B 9. Chang, H.C., and Rongo, C. (2005) Cytosolic tail sequences and subunit interactions are critical for synaptic

calization of glutamate receptors. The Journal of Cell Science: 118:1945-56. lo 10. Umemura, T., Rapp, P., and Rongo, C. (2005) The role of regulatory domain interactions in UNC-43

aMKII localization and trafficking. The Journal of Cell Science 118:3327-3338. C 11. Schaefer, H., and Rongo, C. (2006) KEL-8 is a substrate receptor for Cul3-dependent ubiquitin ligases that egulates synaptic glutamate receptor turnover. Molecular Biology of the Cell 17(3):1250-1260. r

12. Charych, E.I., Akum, B.F., Goldberg, J.S., Jörnsten, R.J., Rongo, C., Zheng, J.Q., and Firestein, B.L. (2006) Activity-independent regulation of dendrite patterning by postsynaptic density protein PSD-95. Journal

f Neuroscience 26(40):10164-76. o 13. Glodowski, D.R., Chen, C. C.-H., Schaefer, H., Grant, B.D., and Rongo, C. RAB-10 regulates glutamate receptor recycling in a cholesterol-dependent endocytosis pathway. (2007) Molecular Biology of the Cell

8(11):4387-96. 1 14. Park, E.C., and Rongo, C. (2009) The ubiquitin ligase RPM-1 and the p38 MAPK PMK-3 regulate the

ndocytosis of AMPA receptors. PLoS ONE 4(1)e4284. e 15. Emtage, L., Chang, C.H., Tiver, R., and Rongo, C. (2009) MAGI-1 modulates AMPA receptor synaptic

calization and behavioral plasticity in response to prior experience. PLoS ONE 4(2):e4613. lo 16. Kramer, L., Shim, J., Previtera, M., Isack, N., Firestein, B.L., Rongo, C. (2009) UEV-1 regulates the

biquitin-dependent turnover of glutamate receptors. Manuscript in preparation. u 17. Park, E.C., Ghose, P., and Rongo, C. (2009) Two p38 MAPK pathways regulate glutamate receptor rafficking and excitoxicity in C. elegans. Manuscript in preparation. t C. Research Support. Ongoing Research Support NIH R01 7/1/02-6/30/12 NS42023 (PI: Rongo) Title: Synapse formation in the C. elegans nervous system. Goal: To characterize several genes for a role in regulating synaptic cell biology in response to learning and memory. Includes our analysis of the function of the PDZ protein MAGI-1, the C. elegans homologs of p38

APK, and the ubiquitin regulatory factor UEV-1 at synapses. M AHA Grant in Aid (PI: Rongo) 7/1/07-6/30/10 American Heart Association Title: The role of p38 MAPK in GluR trafficking, excitotoxicity, and oxidative stress. Goal: To characterize several genes involved in the creation or removal of reactive oxygen species with regard to glutamate receptor trafficking and models of neurodegeneration in C. elegans. Completed Research Support Pew Scholar in Biomedical Sciences (PI: Rongo) 7/1/01-6/30/05 The Pew Charitable Trusts Title: Synapse formation and plasticity in the C. elegans nervous system. Goal: To conduct an in vivo analysis of synapse formation and dynamics in the C. elegans nervous system

sing GFP and photoactivatable GFP reporters. u

Principal Investigator/Program Director (Last, First, Middle): Roth, Monica J.




NAME Monica J. Roth eRA COMMONS USER NAME rothmj




Barnard College, Columbia University A.B. cum laud 1978 Chemistry Albert Einstein College of Medicine M.S. 1982 Biochemistry Albert Einstein College of Medicine Ph.D. 1984 Devel. Biology & Cancer Columbia College of Physicians and Surgeons Postdoc 1988 Biochemistry

A. Positions and Honors. 1978-1979 Graduate Trainee of Dr. Cheng-Wen Wu, Dept. of Biochemistry, Albert Einstein

College of Medicine, N.Y. 1979-1984 Graduate Trainee of Dr. Jerard Hurwitz, Professor and Chairman, Department of Developmental Biology and Cancer, Albert Einstein College of Medicine, N.Y. 1984-1988 Postdoctoral Fellow with Dr. Stephen Goff, Department of Biochemistry, Columbia University, College of Physicians and Surgeons, New York. July 1988 Assistant Professor, Dept. Biochemistry, UMDNJ-RWJ Medical School, Piscataway, N.J. July 1994 Associate Professor, Dept. of Biochemistry, UMDNJ-RWJ Medical School, Piscataway, N.J. July 2000 Professor, Dept. of Biochemistry, UMDNJ-RWJ Medical School, Piscataway, N.J. 1988-present Member: Graduate Program in Biochemistry and Molecular Biology 07/1995-present Member: Cancer Institute of New Jersey 06/94, 95 3/00, 6/02 Ad hoc member Virology Study Section (NIH); 07/95-07/99 Member: Virology Study Section (NIH); 09/94, 06/99, 11/99Member: NCI Program Project Grants: Site visits, Subcommittee C (ad hoc); 6/00, 6/01Ad hoc member: Exp’tal Virology and Medical Biochemistry Study Sections; 5/03 Program Site Visits: FDA and NCI/DRG Ad hoc Member-SSS-H(90)S-Biophysical and Chemical Sciences 6/12/03 Member: Special Study Section ZRG1 SSS-2:Gene Delivery 7/7-8/03. Member: Molecular Carcinogenesis Program Project Cluster Review NCI-C RPRB (Q2) 9/27-29/05 Chairperson: AZI1 AC-M (J2) SARS Program Project Grant Review- NIAID 9/30/04 Grant Reviewer: Fondecyt (Chile), Israel Science Foundation 2004, 2005. Member-Genes and Drug Delivery NIH Study Section 3/2004-06/2008. 12/2008 Ad Hoc Member GDD NIH Study Section (SBIR/STTR), 11/2009 Ad hoc Reviewer ARRA NIH Study Section.. Honors and Awards American Chemical Society Certified Degree in Chemistry (1978); NIH Graduate Trainee 1978-1984; NIH Postdoctoral Trainee, 1984-1985; Fellow of Leukemia Society of America, 1985-1987; Special Fellow of Leukemia Society of America, 1987-1990; Alexander & Alexandrine Sinsheimer Award, 1990; Scholar of the Leukemia Society of America, 1990-1994; UMDNJ Teaching and Service Award-1992; Stohlmann Scholar Award, Leukemia Society of America, 1994; 2001 Organizer of Retroviral Meeting, Cold Spring Harbor, NY. Editorial Board, Virology 2005-present. Patent #4,943,531: S.P. Goff, N. Tanese and M.J. Roth "Expression of enzymatically active reverse transcriptase" (U.S.; issued 7/24/90). Patent #6762031 (US, 07/13/04): Keith Bupp & Monica Roth “Targeting viral vectors to specific cells”. Pending (2008; 60/918,418):“Labeled Biomolecular Compositions and Methods for the Production and Uses Thereof”. Patent: US (based on provisional patents # 61/195,139 and # 61/211,605) “Independently Inducible System of Gene Expression for Single Protein Production (SPP)” Submitted 09/15/2009.

Principal Investigator/Program Director (Last, First, Middle): Roth, Monica J.


B. SELECTED PUBLICATIONS (from a total list of 69 publications) 57. K. Bupp, A. Sarangi, and M. J. Roth (2005) Probing sequence variation in the receptor-targeting domain

of feline leukemia virus envelope proteins using peptide display libraries. J. Virology, 79:1463-1469. PMID: 15650172

58. K. Bupp and M. J. Roth (2005) Alteration and analyses of viral entry with library-derived peptides. In Advances in Virus Research (ElsevierAcademic Press, San Diego, Ca) Karl Maramorosch and Aaron Shatkin, editors. Vol 65, pp. 147-168. PMID: 16387196

59. K. Bupp, A. Sarangi, and M. J. Roth (2006) Selection of feline leukemia virus Envelope proteins from a library by functional association with a murine leukemia virus Envelope. Virology, 351:340-348. PMID: 16678875

60. J. Puglia, T. Wang, C. Smith-Snyder, M. Cote, M. Scher, J. Pelletier, S. John, C. B. Jonsson and M. J. Roth (2006) Revealing domain structure through linker-scanning analysis of the MuLV RNase H, MuLV and HIV-1 Integrase proteins. J. Virol. 80: 9497-9510. PMID: 16973554

61. S. Montano, M. Cote, M. Roth, M. Georgiadis (2006) Crystal structures of oligonucleotides including the integrase processing site of the Moloney murine leukemia virus. Nucl.Acid Res 34: 5353-5360. PMID: 17003051

62. A. Sarangi, K. Bupp, and M.J. Roth (2007) Identification of a retroviral receptor used by an Envelope protein derived by peptide library screening. Proc. Natl. Acad. Sci. USA 104: 11032-11037. PMID: 17581869

63. W. M. Schneider, H. Zheng, M. L. Cote, and M.J. Roth (2007) The 4070A G541R Env mutation decreases the stability and alters the conformation of the TM ectodomain. Virology, 371:165-174. PMID: 17961622

64. J. Vera, B. Valenzuela, M. J. Roth and O. Leon (2008) Characterization of the Long Terminal Repeat single strand tail binding of Moloney-MuLV integrase by crosslinking. Biological Research, 41:69-80.

65. Marie L. Coté, and Monica J. Roth (2008) Murine leukemia virus reverse transcriptase: Structural comparison with HIV-1 reverse transcriptase. Virus Research,134:186-202. PMID: 18294720

66. P. Mazari, D. Linder-Basso, A. Sarangi, Y. Chang, and M. J. Roth (2009) Single-round selection yields a new retroviral Env utilizing GPR172A as a host receptor. PNAS, 106:5848-5853. PMID 19307586

67. W.M. Schneider, M. Inouye, G. Montelione, and M.J. Roth (2009) Independently inducible system of gene expression for condensed single protein production (cSPP) suitable for high efficiency isotope enrichment. J. Struct. Funct. Gen. 10(3):219-25. PMID: 19642019

68. Mao, L., Thangminlal Vaiphei, S., Shimazu, T., Schneider, W., Tang, Y., Mani, R., Roth, M., Montelione, G., Inouye, M. (2009) The E. coli single protein production (cSPP) system for production and structural analysis of membrane proteins J. Struct. Functional Genomics (In press).

B. Active Research Support.

RO1CA49932 Roth, (PI) 09/01/2008-07/31/2012 National Institutes of Health "The Envelope Gene Product of Feline Leukemia Virus" This application develops the retargeting of FeLV to novel receptors, specifically osteosarcoma cells. 3R01CA049932-16A1S1 Roth, PI 06/01/2009 - 09/30/2010. National Institutes of Health, " Targeting Entry of Retroviral/Lentiviral Vectors" ARRA funding for 2 summer students New Jersey Stem Cell Research. 07/01/07-06/30/09. Bioengineering Human ES Stem Cells, Program project Monica J. Roth, PI, Project 4 “Targeting gene delivery to hES cells”, Monica Roth 1RO1 GM088808 Roth, PI 08/01/09-07/31/13. National Institutes of Health “Retroviral integration & HDAC inhibitors” This application studies the C-terminus of Integrase and the effects of HDAC inhibitors on proviral expression.




NAME POSITION TITLE

eRA COMMONS USER NAME (credential, e.g., agency login)


DEGREE INSTITUTION AND LOCATION MM/YY FIELD OF STUDY (if applicable)

Please refer to the application instructions in order to complete sections A, B, C, and D of the Biographical Sketch.


Schaffner, Donald William

Donald W Schaffner Professor

Cornell University, Ithaca, NY BS 05/83 Food Science

Univeristy of Georgia, Athens, GA MS 05/85 Food Science and Tech.

Univeristy of Georgia, Athens, GA PhD 12/88 Food Science and Tech.

A. Positions and Honors. Positions and Employment May 2008 – June 2011. Director of the Center for Advanced Food Technology. Rutgers University. July 2002 – Present. Extension Specialist (Professor). July 1995 – July 2002. Associate Extension Specialist (Associate Professor). February 1989 - June 1995. Assistant Extension Specialist (Assistant Professor). Other Experience and Professional Memberships Special assignment at the request of FAO/WHO at FAO in Rome to work on the development of guidelines for risk characterization for microbiological hazards in food. January, 2008. Special assignment at the request of FAO/WHO at FAO in Rome to work on the development of guidelines for exposure assessment for microbiological hazards in food. October, 2007. Member, Performance objectives, performance criteria and quantitative microbiological risk assessment workshop panel. WHO Collaborating Centre for Risk Assessment of Pathogens in Food and Water. 2006. Member, Joint FAO/WHO Meeting on the development of guidelines for qualitative risk characterization of microbiological hazards in food. 2004 Member, Joint FAO/WHO Consultative process and workshop on provision of scientific advice to Codex and Member States, 2003-2004. Chairman, Joint FAO/WHO Workshop on the development of guidelines for risk characterization of microbiological hazards in food. 2003. Chairman, Joint FAO/WHO Workshop on the development of guidelines for exposure assessment of microbiological hazards in food. 2001-2002.

1



Schaffner, Donald William

Honors International Association for Food Protection (IAFP), Elmer Marth Educator Award. July, 2009. Award presented annually to an individual for outstanding service to the public, IAFP and the arena of education in food safety and food protection. Sustained Research and Impact Award. April, 2008. Award is given annually to those faculty members whose research and scholarship over a period of time have provided significant contributions to their profession, and whose contributions have had direct measurable impact on the communities they serve. School of Environmental and Biological Science and NJAES. B. Selected peer-reviewed publications (in chronological order). 1. Ades G., Brooks S., Engeljohn D., Freier T., Garrett S., Glass K., Harris L., Schaffner D., Scott J., and Zink D. 2010. Parameters for Determining Inoculated Pack/Challenge Study Protocols. Journal of Food Protection, 73(1): 140-202. 2. Hartnett, E., G.M. Paoli, and D.W. Schaffner. 2009. Modeling the Public Health System Response to a Terrorist Event in the Food Supply. Risk Analysis, 29(11) 1506-1520. 3. Dominguez, S.A. and D.W. Schaffner. 2009. Survival of Salmonella in Processed Chicken Products during Frozen Storage. Journal of Food Protection, 72(10) 2088–2092. 4. Maurer Abbot, J., Byrd-Bredbenner, C., Schaffner, D., Bruhn, C., Blalock, L. 2009. Comparison of Food Safety Cognitions and Self-Reported Food Handling Behaviors with Observed Food Safety Behaviors of Young Adults. European Journal of Clinical Nutrition. 63, 572–579. 5. Bowers J., Buchanan R., Christensen B., Fazil A., Frey C., Havelaar A., Kelly L., Lo Fo Wong D., Nasinyama G., Nauta M., Nielson N., Norrung B., Paoli G., Powell M., Roberts T., Schaffner D., Sommer H., Vose D., Wooldridge M., Yoe C. 2009. Risk Characterization of Microbiological Hazards in Food: Guidelines. FAO/WHO [Food and Agriculture Organization of the United Nations/World Health Organization]. Microbiological Risk Assessment Series No. 17. Rome. 142pp. 6. R. Newsome, N. Tran, G.M. Paoli, L.A. Jaykus, B. Tompkin, M. Miliotis, T. Ruthman, E. Hartnett, F.F. Busta, B. Petersen, F. Shank, J. McEntire, J. Hotchkiss, M. Wagner, D.W. Schaffner. 2009. Development of a Risk-Ranking Framework to Evaluate Potential High-Threat Microorganisms, Toxins, and Chemicals in Food. Journal of Food Science. 74(2)R39-R45. 7. Corradini, M.G., M.D. Normand, C. Newcomer, D.W. Schaffner and M. Peleg. 2009. Extracting Survival Parameters from Isothermal, Isobaric and “Iso-concentration” Inactivation Experiments by the “Three End Points Method”. Journal of Food Science. 74(1)R1-R11. 8. Dominguez, S.A. and D.W. Schaffner. 2008. Modeling the growth of Salmonella in raw poultry stored under aerobic conditions. Journal of Food Protection. 71(12) 2429–2435. 9. Christensen B., Ebel E., Egan K., Fazil A., French N., Gelli D., Gorris L., Hartnett E., Hogue A., Karunasagar I., Kasuga F., Kelly L., Liu X., Marshall D., Nasinyama G., Nauta M., Norrung B., Osaka K., Ross T., Schaffner D., Schlosser W., Vanderlinde P., Whiting R., and Wooldridge M. 2008. Exposure assessment of microbiological hazards in foods: Guidelines. FAO/WHO [Food and Agriculture Organization of the United Nations/World Health Organization]. Microbiological Risk Assessment Series No. 7. Rome. 92pp.

2




NAME Shao, Changshun eRA COMMONS USER NAME chshao

POSITION TITLE Associate Research Professor



Qufu Normal University, Qufu, China B.S. 1983 Biology Shandong Medical University, Jinan, China M.S. 1986 Medical Genetics Indiana University, Indianapolis, IN Ph.D. 1998 Med. & Mol. Genetics

A. Positions and Honors. Positions and Employment 1986-1993 Instructor, lecturer of Genetics, Shandong Medical University 1989-1990 Visiting Fellow, Hokkaido University, Japan 1993-1998 Research Assistant, Indiana University School of Medicine, Indianapolis, IN 1999-2001 Postdoctoral/Research Associate, Rutgers University, Piscataway, NJ 2001-2008 Assistant Research Professor, Rutgers University, Piscataway, NJ 2007- Professor (Special Appointment), Shandong University, Jinan, China 2008- Associate Research Professor, Rutgers University, Piscataway, NJ Other Experience and Professional Memberships 2008- Member, Cancer Institute of New Jersey Honors 1989 Sasakawa Scholar in Medical Sciences, Sasakawa Memorial Foundation of Japan 2001 Young Investigator Achievement Award, Environmental Mutagen Society B. Selected peer-reviewed publications (in chronological order). (From more than 40) 1. Shao C and Takagi N. 1990. An extra maternally derived X chromosome is deleterious to early mouse

development. Development 110: 969-975. 2. Shao C and Takagi N. 1991. Karyotypes and X chromosome inactivation in segregants of a murine X-

autosome translocation, T(X;4)37H. Jpn. J. Genet. 66: 433-447. 3. Gong Y, Shao C, Sun Q, Chen B, Jiang Y, Guo C, Wei J, Guo Y. 1994. Genetic study of indirect inguinal

hernia. J. Med. Genet. 31:187-192. 4. Stambrook PJ, Shao C, Stockelman M, Boivin G, Engle SJ, Tischfield JA. 1996. APRT: A versatile in vivo

resident reporter of local mutation and loss of heterozygosity. Environ. Mol. Mutagen. 28:471-482. 5. Shao C, Gupta PK, Sun Y, Sahota A, Tischfield JA. 1996. Complex chromosome mechanisms lead to

APRT loss of heterozygosity in heteroploid cells. Cytogenetics & Cell Genetics 75:216-221. 6. Chen J, Shao C, Lazar V, Srivastava CH, Lee WH, Tischfield JA. 1997. Localization of Group IIc low

molecular weight phospholipase A2 mRNA to meiotic cells in the mouse. J. Cell. Biochem. 64:369-375. 7. Gupta PK, Sahota A, Bye S, Boyadjiev S, Shao C, O'Neill P, Albertini RJ, Stambrook PJ, Tischfield JA.

1997. High frequency in vivo loss of heterozygosity is primarily a consequence of mitotic recombination in normal T lymphocytes of human APRT heterozygotes. Cancer Res. 57:1188-1193.

8. Gupta PK, Shao C, Zhu Y, Sahota A, Tischfield JA. 1997. Loss of heterozygosity analysis in a human fibrosarcoma cell line. Cytogenetics & Cell Genetics 76:214-218.

9. Shao C, Deng L, Henegariu O, Liang L, Raikwar N, Sahota A, Stambrook PJ, Tischfield JA. 1999. Mitotic recombination produces the majority of recessive fibroblast variants in heterozygous mice. Proc. Natl. Acad. Sci. USA 96:9230-9235.

10. Liang L, Deng L, Shao C, Stambrook PJ, Tischfield JA. 2000. In vivo loss of heterozygosity in T cells of B6C3F1 Aprt+/- mice. Environ. Mol. Mutagen. 35:150-157.

11. Shao C, Deng L, Henegariu O, Liang L, Stambrook PJ, Tischfield JA. 2000. Chromosome instability contributes to loss of heterozygosity in mice lacking p53. Proc. Natl. Acad. Sci. USA 97:7405-7410.

12. Wang L. Raikwar N, Deng L, Yang M, Liang L, Shao C, Evan AP, Sahota A, Tischfield JA. 2000. Altered gene expression in kidneys of mice with 2,8-dihydroxyadenine nephrolithiasis. Kidney International 58:528-536.

13. Shao C*, Stambrook PJ, Tischfield JA*. 2001. Mitotic recombination is suppressed by chromosomal divergence in hybrids of distantly related mouse strains. Nature Genetics 28:169-172.

14. Evan AP, Bledsoe SB, Connors BA, Deng L, Liang L, Shao C, Fineberg NS, Grynpas MD, Stambrook PJ, Shao Y, Sahota A, Tischfield JA. 2001. Sequential analysis of kidney stone formation in the Aprt knockout mouse. Kidney International 60:910-923.

15. Shao C, Yin M, Deng L, Stambrook PJ, Doetschman T, Tischfield JA. 2002. Loss of heterozygosity and point mutation at Aprt Locus in T cells and fibroblasts of Pms2-/- mice. Oncogene 21: 2840-2845.

16. Cervantes RB, Stringer JR, Shao C, Tischfield JA, Stambrook PJ. 2002. Embryonic stem cells and somatic cells differ in mutation frequency and type. Proc. Natl. Acad. Sci. USA 99: 3586-3590.

17. Liang L, Shao C, Deng L, Mendonca MS, Stambrook PJ, Tischfield JA.2002. Radiation-induced genetic instability in vivo depends on p53 status. Mutat. Res. 502: 69-80.

18. Shao C*, Deng L, Chen Y, Kucherlapati R, Stambrook PJ, Tischfield JA*. 2004. Mlh1 mediates tissue-specific regulation of mitotic recombination. Oncogene 23: 9017-9024.

19. Liang L, Deng L, Chen Y, Li GC, Shao C, Tischfield JA. 2005. Modulation of DNA end joining by nuclear proteins. J. Biol. Chem. 280: 31442-31449. 20. Zou Y, Liu Q, Chen B, Zhang X, Guo C, Zhou H, Li J, Gao G, Guo Y, Yan C, Wei J, Shao C, Gong Y.

2007. Mutation in CUL4B, a member of cullin-RING ubiquitin ligase complex, causes X-linked mental retardation. Am. J. Hum. Genet. 80:561-566.

21. Liang L, Mendonca MS, Deng L, Nguyen SC, Shao C*, Tischfield JA. 2007. Reduced apoptosis and increased deletion mutations in vivo in mice exposed to repeated ionizing radiation. Cancer Res. 67:1920-1917.

22. Liang L, Deng L, Mendonca MS, Chen Y, Stambrook PJ, Shao C, Tischfield JA. 2007. X-rays induce distinct patterns of somatic mutation in fetal versus adult hematopoietic cells. DNA repair 6:1380-1385.

23. Barrera-Oro J, Liu TY, Gorden E, Kucherlapati R, Shao C, Tischfield JA. 2008. Role of the mismatch repair gene, Msh6, in suppressing genome instability and radiation-induced mutations. Mutat. Res. 642:74-79.

24. Liang L, Deng L, Nguyen SC, Zhao X, Maulion C, Shao C, Tischfield JA. 2008. Human DNA ligases I and III, but not ligase IV, are required for microhomology-mediated end joining of DNA double-strand breaks. Nucleic Acids Res. 36:3297-3310.

25. Lin P, Li J, Liu Q, Mao f, Li J, Qiu R, Hu H, Song Y, Yang Y, Gao G, Yan C, Yang W, Shao C, Gong Y. 2008.A missense mutation in SLC33A1, which encodes the acetyl-CoA transporter, causes autosomal dominant spastic paraplegia (SPG42). Am. J. Hum. Genet. 83:752-759.

26. Liu Z, Liu Q, Xu B, Wu J, Guo C, Zhu F, Yang Q, Gao G, Gong Y*, Shao C*. 2009. Berberine induces p53-dependent cell cycle arrest and apoptosis of human osteosarcoma cells by inflicting DNA damage. Mutat. Res. 662:75-83.

27. Zhu Y, Sun Z, Han Q, Liao L, Wang J, Bian C, Li J, Yan X, Liu Y, Shao C, Zhao RC. 2009. Human mesenchymal stem cells inhibit cancer cell proliferation by secreting DKK-1. Leukemia 23:925-933.

28. Zhou H, Shang L, Li X, Zhang X, Gao G, Guo C, Chen B, Liu Q, Gong Y*, Shao C*. 2009. Resveratrol augments the canonical Wnt signaling pathway in promoting osteoblastic differentiation of multipotent mesenchymal cells. Exp. Cell Res. 315:2953-2962.

29. Shao C*, Liang L, Zhao X, Chen Y, Zheng B, Chen J, Luo M, Tischfield JA. 2009. Mutagenesis in vivo in T cells of p21-deficient mice. Mutat. Res. 670: 103-106.

30. Shang L, Zhou H, Xia Y, Wang H, Gao G, Chen B, Liu Q, Shao C, Gong Y*. 2009. Serum withdrawal up-regulates human SIRT1 gene expression via a p53-dependent manner. J. Cell. Mol. Med. 13: 4176-4184

31. Zou Y, Mi J, Cui J, Lu D, Zhang X, Guo C, Gao G, Liu Q, Chen B, Shao C*, Gong Y*. 2009. Characterization of Nuclear Localization Signal in N-terminus of CUL4B and Its Essential Role in Cyclin E Degradation and Cell Cycle Progression. J. Biol. Chem. 284: 33320-33332.

32. Zhao X, Ren G, Liang L, Ai PZ, Zheng B, Tischfield JA, Shi Y*, Shao C*. 2010. IFNgamma induces expansion of Lin-Sca-1+c-Kit+ cells. Stem Cells 28:122-126.

33. Ren G, Zhao X, Zhang L, Zhang J, Ling W, Roberts AI, Shao C, Shi Y. 2010. Inflammatory cytokine-induced ICAM-1 and VCAM-1 in mesenchymal stem cells are critical for immunosuppression. J. Immunology 184: 2321-2328.

34. Tereshchenko IV, Chen Y, McDaniel LD, Schultz RA, Tischfield JA, Shao C*. 2010. Small scale genetic alterations contribute to increased mutability at the X-linked Hprt locus in vivo in Blm hypomorphic mice. DNA Repair 9:551-557.

(* Corresponding author). C. Research Support

Completed Research Support New Jersey Stem Cell Research Grant. Shao (PI) 07/01/2007-06/30/2009 Stem cell origin of spontaneous and radiation-induced mutations recovered in T cells This project is focused on the origin of somatic mutations in T cells Role: PI RO1ES11633 Tischfield (PI) 09/15/02 - 07/31/08 NIH/NIEHS – Mouse Model for Chemical and Radiation Mutagenesis This project is basic research on a mouse model for loss of heterozygosity and DNA repair. Major effort is on dissecting the components of mitotic recombination in the mouse. Role: Co-Investigator New Jersey Stem Cell Research Grant Tischfield (PI) 01/01/06-12/31/07 Genetic and structural analysis of mouse ES cells and their derivatives This project is to study the mechanisms underlying the high genomic integrity in embryonic stem cells Role: Co-Investigator


Principal Investigator/Program Director (Last, First, Middle): Singson, Andrew W.



NAME Andrew W. Singson eRA COMMONS USER NAME andrewsingson

POSITION TITLE Associate Professor, Genetics



University of California, Davis. CA B.S. 1984-1989 Genetics University of California, San Diego, CA Ph.D. 1989-1995 Biology Emory University, Atlanta, GA Postdoc 1995-2000 Genetics/Fertilization

A. Education and Research Experience and Positions: 1984-1989 University of California, Davis

College of Agriculture and Environmental Sciences. Major: Genetics. Bachelor of Science with Honors.

1987-1989 Undergraduate Research. Research Technician / Electron Microscopist. Laboratory of Dr. James Boyd. Department of Genetics. University of California, Davis.

1989-1995 University of California, San Diego. Doctoral Program in Biology. Dr. James W. Posakony, Advisor.

1995-2000 Emory University. Postdoctoral Training. Laboratory of Dr. Steven W. L’Hernault.

2000-2006 Assistant Professor. Rutgers University. Waksman Institute with joint appointment in the Department of Genetics

2006-present Associate Professor. Rutgers University. Waksman Institute with joint appointment in the Department of Genetics

B. Publications in Current Field 1. J. M. Parry, A. J. Lefkovith, J. S. Hang, J. Ohm, R. Klancer, M. H. Zegarek, R. Maruyama, N. V. Velarde, F. Piano, B. D. Grant and A. Singson (2009). EGG-4 and EGG-5 link events of the oocyte-to-embryo transition with meiotic progression in C. elegans. Current Biology. 19: 1752-1757. 2. K. Chih-Chien Cheng, R. Klancer, A. Singson and G. Seydoux. (2009) Regulation of MBK-2/DYRK by CDK-1 and the pseudophosphatases EGG-4 and EGG-5 during the oocyte-to embryo transition. Cell. 139: 560-572. 3. P. Kadandale and A. Singson. (2009) The dynamics of EGG-2. Visions: the art of science. Molecular Reproduction and Development. 76: 429. 4. P. Kadandale, I. Chatterjee and A. Singson. (2009) Germline transformation of Caenorhabditis elegans by injection. Microinjection Methods and Applications. David Carroll (Ed.). Series: Methods in Molecular Biology, 518: 123-133. 5. A. Singson, J. S. Hang, J. M. Parry. (2008) Genes required for the common miracle of fertilization in Caenorhabditis elegans. International Journal of Developmental Biology. 52: 647-656.



6. J. S. Hang B.D. Grant and A. Singson. (2008) Meiotic Maturation: Receptor Trafficking Is the Key. Current Biology. 18: R416-R418. 7. R. Maruyama, N. V. Velarde, R. Klancer, S. Gordon, P. Kadandale, J. M. Parry, J. S. Hang, J. Rubin, A. Stewart-Michaelis, P. Schweinsberg, B. D. Grant, F. Piano, A. Sugimoto and A. Singson. (2007) EGG-3 regulates cell-surface and cortex rearrangements during egg activation in Caenorhabditis elegans. Current Biology. 17: 1555-1560. 8. R. Maruyama and A. Singson. (2006) Taking care of Dad’s DNA. Genome Biology 7: 244.1-244.3. 9. I. Chatterjee P. Kadandale and A. Singson. (2006) Meiotic diapause: how a sperm signal sets you free. Current Biology. 16: R496-R499. 10. A. Singson. Sperm activation: time and tide wait for no sperm. (2006) Current Biology 16: R160-R162. 11. B. Geldziler, I. Chatterjee, P. Kadandale, E. Putiri, R. Patel and A. Singson. (2006) A comparative study of sperm morphology, cytology and activation in Caenorhabditis elegans, Caenrohabditis remanei and Caenorhabditis briggsae. Development, Genes and Evolution. 216: 198-208. 12. E. J. Gleason, W. C. Lindsey, T. L. Kroft, A. W. Singson and S. W. L’Hernault. (2006) spe-10 Encodes a DHHC-CRD zinc finger membrane protein required for ER/golgi membrane morphogenesis during Caenorhabditis elegans spermatogenesis. Genetics. 172: 145-158. 13. P. Kadandale, A. Stewart-Michaelis, S. Gordon, J. Rubin, R. Klancer, P. Schweinsberg, B. D. Grant and A. Singson. (2005) The egg surface LDL-receptor-repeat containing proteins EGG-1 and EGG-2 are required for fertilization in Caenorhabditis elegans. Current Biology. 15: 2222-2229. 14. B. Geldziler, I. Chatterjee and A. Singson. (2005) The genetic and molecular analysis of spe-19, a gene required for sperm activation in Caenorhabditis elegans. Developmental Biology. 283: 424-436. 15. I. Chatterjee, A. Richmond, E. Putiri, D. Shakes and A. Singson. (2005) The Caenorhabditis elegans spe-38 gene encodes a novel four-pass integral membrane protein required for sperm function at fertilization. Development. 132: 2795-2808. 16. P. Kadandale, B. Geldziler, M, Hoffmann and A. Singson. (2005) Use of SNPs to determine the breakpoints of complex deficiencies, facilitating gene mapping in Caenorhabditis elegans. BMC Genetics. 6: 28. 17. B. Geldziler, P. Kadandale and A. Singson. (2004) Molecular genetic approaches to studying fertilization in model systems. Reproduction. 127: 409-416. 18. E. Putiri, S. Zannoni, P. Kadandale, and A. Singson. (2004) Functional domains and temperature-sensitive mutations in SPE-9, an EGF repeat-containing protein required for fertility in Caenorhabditis elegans. Developmental Biology. 272: 448-459. 19. P. Kadandale and A. Singson. (2004) Oocyte production and sperm utilization patterns in semi-fertile strains of Caenorhabditis elegans. BMC Developmental Biology, 4: 3. 20. S. Zannoni, S. W. L’Hernault and A. W. Singson. (2003) Dynamic localization of SPE-9 in sperm: a protein required for sperm-oocyte interactions in Caenorhabditis elegans. BMC Developmental Biology. 3: 10. 21. J. Bandyopadhyay, J. Lee, J. Lee, J. I. Lee, J. R. Yu, C. Jee, J. H. Cho, S. Jung, M. H. Lee, S. Zannoni, A. Singson, H. S. Koo and J. Ahnn. (2002) Calcineurin, a component of G-protein coupled phosphorylation



pathways, is involved in movement, fertility, egg laying and growth in C. elegans. Molecular Biology of the Cell. 13: 3281-3293. 22. B. Park, D. Lee, S. Jung, J. Yu, K. Choi, J. Y. Kwon, J. Lee, J. Lee, A. Singson, W. K. Song, C. S. Park, D. H. Kim, J. Bandyopadhyay and J. Ahnn. (2001) Calreticulin, a calcium-binding molecular chaperone is required for stress response and sperm fertility in C. elegans. Molecular Biology of the Cell. 12: 2835-2845. 23. A. Singson, S. Zannoni and P. Kadandale. (2001) Molecules that function in the steps of fertilization. Cytokine & Growth Factor Reviews. 12: 299-304. 24. A. Singson. (2001) Every sperm is sacred: fertilization in Caenorhabditis elegans. Developmental Biology. 230: 101-109. 25. R. E. Navarro, E. Y. Shim, Y. Kohara, A. Singson and T.K. Blackwell. (2001) cgh-1, a conserved predicted RNA helicase required for gametogenesis and inhibition of germline apoptosis in C. elegans. Development. 128: 3221-3232. 26. S. W. L’Hernault and A. Singson. (2000) Developmental genetics of spermatogenesis in the nematode Caenorhabditis elegans. In: “The Testes: From Stem Cell to Sperm Function”, Serono Symposium USA, 109-119. 27. A. Singson, K. L. Hill and S. W. L’Hernault. (1999) Sperm competition in the absence of fertilization in Caenorhabditis elegans. Genetics. 152: 201-208. 28. A. Singson, K. B. Mercer and S. W. L’Hernault. (1998) The C. elegans spe-9 gene encodes a sperm transmembrane protein that contains EGF-like repeats and is required for fertilization. Cell. 93: 71-79. C. Research Support National Institutes of Health. Gamete Interactions in Caenorhabditis elegans. R01HD054681-06. 4/1/08 – 3/31/13. National Institutes of Health. Gamete Interactions in Caenorhabditis elegans. R56 Directors Bridge Award 9/30/07 – 3/31/08. R56HD54681. National Institutes of Health. Gamete Interactions in Caenorhabditis elegans. R01 GM63089-04. 5/1/01-4/31/06. Johnson & Johnson Discovery Award 80% Charles & Johanna Busch Biomedical Funds 20% Phenotypic and molecular analysis of egg genes in Caenorhabditis elegans. 7/1/04 - 5/1/06. National Science Foundation Minority Postdoctoral Starter Grant. Sperm-Egg Interactions in Caenorhabditis elegans. IBM 0000182. 6/1/00-5/31/01. Charles & Johanna Busch Biomedical Grant. Genetic and Molecular Analysis of Genes Required for Fertilization in C. elegans. 7/1/00-5/1/02. Reinvest in Rutgers Equipment Grant. Co-PI with Dr. Vershon and Dr. Sofer. Fluorescence Microscopy and Video Analysis of C. elegans. 12/6/01. Johnson & Johnson Discovery Award. Identification of egg components required for Fertilization in Caenorhabditis elegans. 7/1/02 - 5/1/04. New Jersey SROA-7. High Speed Automated Analysis of the Nematode C. elegans.



Project chair and author. 11/1/02 - 10/31/03. D. Study Section Appointments 2009 - 2013. NIH Reproduction Andrology and Gynecology Study Section Standing Member. 2006 - 2011. American Cancer Society Development, Differentiation and Cancer Study Section Member.

Grant and Contract Support Name: Jay A. Tischfield Current Grant and Contract Support: NIH C06RR030323 “Rutgers University Cell and DNA Repository Renovation” Jay A. Tischfield, Principal Investigator (0.27 academic) Project period and award: 03/04/10 – 03/03/12; $9,492,078 (total direct costs) NIH/NIAAA AA008401 (since 1989) "Collaborative Studies on the Genetics of Alcoholism” Jay A. Tischfield/Porjesz, Co-Principal Investigator (.90 academic) Project period and award: 09/01/09 - 08/31/14; $1,507,967 (total direct costs) NIH/NIDDK HHSN267200800018C (since 2002) “NIDDK Genetics Repository” Jay A. Tischfield, Principal Investigator (1.80 academic) Project period and award: 07/14/08 – 07/13/13; $10,353,408 (total direct costs) NIH/NIMH U24 MH068457 -07, -07S1, -07S2 (since 1998) “NIMH Center for Collaborative Genetic Studies”

Jay A. Tischfield, Principal Investigator (with J. Rice Ph.D. Wash. Univ. School Med.) (2.25 academic)

Project period and award: 9/26/08 – 05/31/13; $44,794,927 (total direct costs) NIH/NIDA HHSN271200900012C (since 1999) “NIDA Center for Genetics Studies”


Project period and award: 04/30/09 –04/29/12; $7,468,491 (total direct costs) Simons Foundation (since 2007) “Simons Simplex Collection Cell & DNA Repository” Jay A. Tischfield, Principal Investigator (1.08 academic) Project period – 7/1/09 – 06/30/11; $6,472,072 (total direct costs) SNJ FY 09-10 NJ Center for Tourette Syndrome & Assoc. Disorders, Inc. (since 2005)

“Center of Excellence for Tourette Syndrome & Associated Disorders” Jay. A. Tischfield, Principal Investigator (.18 academic) Project Period – 07/01/09 – 06/30/10; $250,000 (total direct costs) NIH/NIMH RC2 MH089951 “Integration of Genomics & Transcriptomics in Normal Twins & Major Depression”

Jay A. Tischfield, Co-Investigator/Site Principal Investigator (with Sullivan The University of North Carolina at Chapel Hill) (0.18 academic)

Project period and award: 09/30/09 - 08/31/11; $3,126,847 (total direct costs) NIH/NIMH & NHGRI R01MH089482 “5/5- Elucidating the Genetic Architecture of Autism by Deep Genomic Sequencing”

Jay A. Tischfield, Co-Investigator/Site Principal Investigator (with Sutcliffe Vanderbilt University) (0.18 academic)

Project period and award: 09/30/09 - 08/31/11; $2,800,667 (total direct costs)

NIH/NIMH RC2 MH090030 “Joint Mapping of Genome-Wide Gene Expression and Association in a Schizophrenia Dataset”

Jay A. Tischfield, Co-Investigator/Site Principal Investigator (with Sanders NorthShore University HealthSystem Research Institute) (0.09 academic)

Project period and award: 09/30/09 - 08/31/10; $55,965 (total direct costs) NIH/NIMH RC2 MH089916 “Depression Susceptibility Genes and Networks: expression, eQTL and GWAS analysis”

Jay A. Tischfield, Co-Investigator/Site Principal Investigator (with Levinson StanfordUniversity) (0.09 academic)

Project period and award: 09/30/09 - 08/31/11; $235,914 (total direct costs) NIH/NIAID NO1AI15416 Immune Tolerance Network “Central Cell Processing Core Facility”

Jay A. Tischfield, Principal Investigator/ Site Principal Investigator (with Bluestone University of California at San Francisco) (0.09 academic)

Project period and award: 01/01/07 – 09/30/10; $1,307,139 (total direct costs) Completed Grant and Contract Support: NIH/NIAAA AA008401 (et al) "Collaborative Study on the Genetics of Alcoholism” Jay A. Tischfield/Porjesz, Co-Principal Investigator (.90 academic) Project period and award: 09/01/04 - 08/31/09; $1,184,544 (total direct costs) Simons Foundation “Simons Simplex Collection Cell & DNA Repository” Jay A. Tischfield, Principal Investigator (0.45 academic) Project period – 7/1/07 – 06/30/09; $5,347,768 (total direct costs) NJ Center for Tourette Syndrome & Associated Disorders “The Tourette Syndrome Sharing DNA and Cell Resource” Jay. A. Tischfield, Principal Investigator (.18 academic)

Project Period – 07/01/05 – 06/30/09; $798,750 (total direct costs) NIH/NIDA N01DA-4-7745 “NIDA Center for Genetic Studies”


Project period and award: 05/01/04 –04/30/09; $10,645,632 (total direct costs) SNJ-Commission on Science & Technology 06-2042-014-85 “Genetic and Structural Analysis of Mouse ES Cells and their Derivatives” Jay A. Tischfield, Principal Investigator (0.72 academic) Project period and award: 01/01/06– 12/31/08; $260,870 (total direct costs) NIH/NIMH U24 MH 068457 “NIMH Center for Collaborative Genetic Studies” Jay A. Tischfield, Principal Investigator (2.25 academic) Project period and award: 07/01/03– 09/30/08; $28,242,804 (total direct costs) HRSA C76HF00732 “Health Care Facilities and Other Construction”

Jay A. Tischfield, Principal Investigator (0.09 academic) Project period and award: 09/01/03 – 08/31/08; $2,753,078 (total direct costs) NIH/NIEHS R01 ES11633

“Mouse Model for Chemical and Radiation Mutagenesis” Jay A. Tischfield, Principal Investigator (1.35 academic)

Project period and award: 9/15/02 - 7/31/08; $1,244,125 (total direct costs) NIH/NIDDK N01DK-3-2610 “NIDDK Genetics Repository” Jay A. Tischfield, Principal Investigator (1.80 academic) Project period and award: 07/01/02 – 07/13/08; $11,758,531 (total direct costs) NIH/NIAAA R01 AA012558 “IRPG8 R01: Novel Phenotypes for Genetics of Alcoholism” Jay A. Tischfield, Principal Investigator (0.27 academic) Project period and award: 09/01/99 – 04/30/08; $1,151,316 (total direct costs)





NAME Tischfield, Jay A.

POSITION TITLE Chair, Department of Genetics Director, Human Genetics Institute

eRA COMMONS USER NAME (credential, e.g., agency login) Tischfield EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable.)


Brooklyn College, Brooklyn, NY B.S. 1967 Biology Yale University, New Haven, CT M.Ph. 1969 Biology Yale University, New Haven, CT Ph.D. 1973 Biology

A. Personal Statement The Rutgers Cell and DNA Repository, which I founded twelve years ago and have continuously directed, is the leader in innovative repository and molecular analysis services in support of projects aimed at understanding the common, complex disorders that have a genetic etiology. We are the Center for Genetic Studies or Repository for four NIH institutes and numerous charitable or private foundations. We utilize state of the art techniques and informatics but, most importantly, we are dedicated to the service of the subjects who have provided these samples. We regard informed consent as a contract in which we are signatories, and we accept an obligation to see that samples have the best protection, both ethically and scientifically. This is our guiding principle. B. Positions and Honors Positions and Employment 1972-1978 Assistant Professor, Biology and Pediatrics, Case Western Reserve University, Cleveland, OH 1978-1986 Assoc. Professor, Anatomy, Cell & Molec. Biol., & Pediatrics, Med Col of GA, Augusta, GA 1987-1998 Professor, Medical and Molecular Genetics, Indiana Univ. School of Medicine, Indianapolis, IN 1989-2008 Adjunct (Volunteer) Professor, Cell Biol, Neurobiol & Anat, Univ. of Cincinnati Coll. of Med, OH 1998- Professor II and Chair, Dept. of Genetics, Rutgers Univ., Piscataway, NJ 1999 Professor, Pediatrics and Psychiatry, Robert Wood Johnson Med School, Piscataway, NJ 2000- Professor, Toxicology, EOHSI, Rutgers Univ., Piscataway, NJ 2001- Professor, Center for Alcohol Studies, Rutgers Univ., Piscataway, NJ 2005 - Director, Human Genetics Institute of New Jersey, Piscataway, NJ Other Experience (selected, since 1990) 1987-1998 Director, Division of Molecular Genetics, Indiana Univ. School of Medicine, Indianapolis, IN 1989-1998 Director, Cell and DNA Repositories, Indiana Univ. School of Medicine, Indianapolis, IN 1992-2007 Editorial Advisory Board, J. of Molecular Medicine 1994-1996 Vice President, Indiana University Medical Genetics, Inc., Indianapolis, IN 1998- Scientific Director, Rutgers Univ. Cell and DNA Repositories (RUCDR) 1999 - Internal Advisory Board, Cancer Center of New Jersey 1998-1999 Scientific Review Panel, New Jersey Governor’s Council on Autism 2001-2005 Scientific Advisory Board, Genome Institute of Singapore 2001- Editorial Board, Mutation Research 2006 - Steering Committee, Stem Cell Institute of NJ 2006- Scientific Advisory Board, Center for Treatment of Addictions, Rockefeller University, NY 2005 - Advisor, Singapore Tissue Network 2004 - Member, Tourette Syndrome Center of Excellence Task Force Honors (since 1990) 1990 Distinguished Alumnus Award and Medal, Brooklyn College of the City University of NY



1994 Elliot Osserman Award for Distinguished Service in Support of Cancer Research 1996-2000 Founding Advisor, Human Genetics Program, Inst. for Molecular and Cell Biology, Singapore 1999- Duncan and Nancy MacMillan Endowed Chair in Genetics, Rutgers Univ., Piscataway, NJ 2007 Fellow, American Association for the Advancement of Science Professional Certification 1987- Diplomate, American Board of Medical Genetics Ph.D. Medical Geneticist (current) 1993- Diplomate, American Board of Medical Genetics, Clinical Molecular Geneticist (current) 1993- Founding Fellow, American College of Medical Genetics

C. Selected Peer-reviewed Publications (Selected from more than 180) 1. Chen J, Chen Y, Capizzi S, Yang M, Deng L, Bledsoe SB, Evan AP, Tischfield JA, Sahota A. 2,8-

Dihydroxyadenine Nephrolithiasis Induces Developmental Stage-specific Alterations in Gene Expression in Mouse Kidney. Urology. 2009 Dec 24. [Epub ahead of print]

2. Xuei X, Flury-Wetherill L, Dick D, Goate A, Tischfield J, Nurnberger J Jr, Schuckit M, Kramer J, Kuperman S, Hesselbrock V, Porjesz B, Foroud T, Edenberg HJ. GABRR1 and GABRR2, encoding the GABA-A receptor subunits rho1 and rho2, are associated with alcohol dependence. Am J Med Genet B Neuropsychiatr Genet. 2009 Jun 17. [Epub ahead of print] PMC Journal-In Process

3. Heiman GA, King RA, Tischfield JA. New Jersey Center for Tourette Syndrome Sharing Repository: methods and sample description. BMC Med Genomics. 2008 Nov 26;1:58. PMCID: PMC2605751

4. Wetherill L, Schuckit MA, Hesselbrock V, Xuei X, Liang T, Dick DM, Kramer J, Nurnberger JI Jr, Tischfield JA, Porjesz B, Edenberg HJ, Foroud T. Neuropeptide Y receptor genes are associated with alcohol dependence, alcohol withdrawal phenotypes, and cocaine dependence. Alcohol Clin Exp Res. 2008 Dec;32(12):2031-40. Epub 2008 Sep 25. PMCID: PMC2650441

5. Chen AC, Tang Y, Rangaswamy M, Wang JC, Almasy L, Foroud T, Edenberg HJ, Hesselbrock V, Nurnberger J Jr, Kuperman S, O'Connor SJ, Schuckit MA, Bauer LO, Tischfield J, Rice JP, Bierut L, Goate A, Porjesz B. Association of single nucleotide polymorphisms in a glutamate receptor gene (GRM8) with theta power of event-related oscillations and alcohol dependence. Am J Med Genet B Neuropsychiatr Genet. 2009 Apr 5;150B(3):359-68. PMCID: PMC2660384 [Available on 2010/4/5]

Ongoing Research Support (3 of 9)

1. NIH C06RR030323 03/04/10 – 03/03/12 NIH - “Rutgers University Cell and DNA Repository Renovation” Construction grant to renovate space for robotics suite and computational genetics group. Role: Principal Investigator

2. U24 MH068457-07, 06S1, -07S1, -07S2 Tischfield (PI) 09/30/98 - 05/31/13 NIH/NIMH - NIMH Center for Collaborative Genetic Studies on Mental Disorders The major goals of this cooperative agreement are to establish a repository of DNA, cell lines, RNA/cDNA and other biomaterials from individuals with various mental disorders and to maintain a genotype and phenotype database of subjects and to distribute these to NIMH-approved researchers. We also develop new molecular analysis protocols for biosamples, and statistical/computational methods for genetic data from the NIMH Genetics Initiative. As a supplement to this grant and NIAAA grant 5U10 AA008401, we are conducting a comparison study of the transcriptome and CNVs from blood, fresh lymphocytes and cell lines of different ages derived from TD subjects. Role: Principal Investigator

3. 5U10 AA008401 Porjesz/Tischfield (Co-PI) 09/01/89 - 08/31/14 NIH/NIAAA - Collaborative Study on the Genetics of Alcoholism This project has seven participating institutions and aims to identify genes for vulnerability to alcoholism and alcohol abuse. Rutgers maintains the NIAAA/COGA Sharing Repository and conducts gene and transcriptome expression studies and functional studies on blood and cell lines. Role: Co-Investigator (Site PI)




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http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Heiman%20GA%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus

http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22King%20RA%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus

http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Tischfield%20JA%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus







ANDREW KEITH VERSHON

Professional Preparation: Bennington College, Bennington, VT. Biology B.A. 1979 Massachusetts Institute of Technology Cambridge, MA. Ph.D. Biochemistry 1986 Univ. of Calif., San Francisco, CA Postdoctoral Fellow, Microbiology, 1987-1991 Appointments: 6/03- Professor, Waksman Institute of Microbiology and Department of Molecular

Biology and Biochemistry, Rutgers University, Piscataway, NJ 9/02- Director, Waksman Student Scholars Program, Rutgers University 7/02- Undergraduate Chair, Dept of Molecular Biology and Biochemistry, Rutgers

University 6/00- Director, Joint Graduate Program in Microbiology and Molecular Genetics Rutgers

University and University of Medicine and Dentistry of NJ, Piscataway, NJ 6/97-5/03 Associate Professor, Waksman Institute of Microbiology and Department of

Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 1/92-5/97 Assistant Professor, Waksman Institute of Microbiology and Department of

Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 11/80-9/81 Scientist, Dept. of Biology, Massachusetts Institute of Technology, Cambridge, MA 6/80-11/80 Research Assistant, University of Massachusetts Medical School, Worcester, MA 6/79-6/80 Research Assistant, Hoffmann-LaRoche Pharmaceutical Co., Nutley, NJ Support: National Science Foundation Discovery Grant (DRL 0733255) 9/01/07 - 8/31/11 (PI)

Bioinformatics: Learning by Doing Total Award $1,799,937. This award is to fund the development and testing of an on-line DNA Sequence Analysis Program (DSAP) for use by high school students and their teachers in the analysis and publication of novel DNA sequences.

National Science Foundation ESI ITEST (DRL 0737574 ) 9/01/07 - 8/31/10 (PI) HiGene: A Genome Sequencing Project for High Schools. Total Award $1,186,829. This award is to fund a research project and outreach program for high school students and their teachers in central New Jersey.

National Science Foundation ESI ITEST (DRL 0737574 ) 9/01/09 - 8/31/10 (PI) Supplement for HiGene: A Genome Sequencing Project for High Schools for establishing HiGene satellite sites in Maryland and Texas. Total Award $97,207.

Publications (Selected from 54 Total): Hanlon, S.E., Xu, Z., Norris, D.N., and Vershon, A. K. (2004) Analysis of the Meiotic Role of

the Mitochondrial Ribosomal Proteins Mrps17 and Mrpl37. Yeast 21, 1241-1252.

Nagaraj, V.H., Flanagan, R.O., Bruning, A.R., Mathias, J.R. Vershon, A. K., and Sengupta, A. M. (2004) Identification of a1-α2 binding sites in the yeast genome. BMC Genomics 5, 59

Mathias, J.R. Hanlon, S.E., Flanagan, R.O., Sengupta, A. M. and Vershon, A.K. (2004) Repression of the yeast HO gene by the MATα2 and MATa1 homeodomain proteins. Nucleic Acid Res. 32, 6469-6478.

Abraham, D. and Vershon, A.K. (2005) The N-terminal arm of Mcm1 affects the transcription of a subset of genes associated with the cell wall. Euk. Cell 4, 1808-1819

Carr, E.A., Charney, J., Sofer, W., and Vershon, A.K. (2006) An integrated molecular biology research project for high school students. American Biology Teacher

Moore, M., Shin, M., Schindler, K., Bruning, A., Vershon, A.K. and Winter E. (2007) Arg-Pro-X-Ser/Thr-Ala is a consensus phosphoacceptor sequence for the meiosis-specific Ime2 protein kinase in Saccharomyces cerevisiae. Biochem. 46, 271-278.

Mead, J., McCord, R, Mead, J., Youngster, L., Sharma, M., Gartenberg, M., and Vershon, A. K. (2007) Swapping the gene-specific and regional silencing specificities of the Hst1 and Sir2 histone deacetylases. Mol. Cell. Biol. 27, 2466-2475.

Teaching and Related Activities (partial list):

Faculty of Arts and Sciences Distinguished Contributions to Undergraduate Education Award

Introduction to Molecular Biology and Biochemistry Research (694:315). (Course coordinator and instructor). This is a molecular biology lecture and lab course taken by Molecular Biology & Biochemistry majors in their junior year. This course was initiated spring 1993 and over 1000 students have taken this course. Developed course structure; designed laboratory manual and procedures; acquired funding, reagents and equipment for the laboratory sections; advised and placed undergraduate students in research laboratories. http://mbb.rutgers.edu/315.html

Honors Introduction to Molecular Biology and Biochemistry Research (694:215). (Course coordinator and instructor). This is a molecular biology lecture and lab course for first year Rutgers undergraduate students who have placed out of the General Biology with Advanced Placement credits. This course was initiated in fall 2006 and 128 students have taken this course. http://mbb.rutgers.edu/215.html

Precollege Independent Research in Molecular Biology course (119:105) (Course coordinator and instructor) This a college level course for advanced high school students to conduct independent bioinformatics research projects. Students presented posters at the North Jersey Regional Science Fair. http://avery.rutgers.edu/WSSP/StudentScholars/105/index.html

Waksman Student Scholars Program. (Director) This is a high school science outreach program that currently serves 28 schools and almost 400 students in NJ, PA, MD and TX. Directed program, acquired funding, provided lectures and assignments on bioinformatics during the summer institute and follow-up meetings throughout the academic year. http://morgan.rutgers.edu

http://mbb.rutgers.edu/315.html

http://mbb.rutgers.edu/215.html

http://avery.rutgers.edu/WSSP/StudentScholars/105/index.html

http://morgan.rutgers.edu

Principal Investigator/Program Director (Last, first, middle): Walworth, Nancy C.

+ PHS 398/2590 (Rev. 05/01) Page ___12___ Biographical Sketch Format Page + Number pages consecutively at the bottom throughout the application. Do not use suffixes such as 3a, 3b.



NAME Nancy C. Walworth, Ph.D. eRA COMMONS USER NAME nwalworth

POSITION TITLE Professor of Pharmacology



Massachusetts Institute of Technology, Cambridge, MA

B.S. 1985 Life Sciences

Yale University, New Haven, CT Ph.D. 1990 Cell Biology Cold Spring Harbor Laboratory, CSH, NY post-doc 1993 Cell Cycle Control The Netherlands Cancer Institute, Amsterdam, The Netherlands

post-doc 1994 Cell Cycle Control

A. Positions and Honors Positions and Employment 1982-85 Research Assistant MIT, Dept. of Nutrition and Food Science, laboratory of Dr. M.F. Holick, 1985-90 Graduate Student Yale University, Dept. of Cell Biology, laboratory of Dr. Peter Novick 1990-93 Post-doctoral Fellow, Cold Spring Harbor Laboratory, laboratory of Dr. David Beach 1993-94 Post-doctoral Fellow, The Netherlands Cancer Institute, laboratory of Dr. Rene Bernards 1994-2001 Assistant Professor, Dept. of Pharmacology, UMDNJ/Robert Wood Johnson Medical School 1995- Member, The Cancer Institute of New Jersey 2001-2005 Associate Professor, Dept. of Pharmacology, UMDNJ/Robert Wood Johnson Medical School 2005- Professor, Dept. of Pharmacology, UMDNJ/Robert Wood Johnson Medical School Professional Memberships American Association for the Advancement of Science American Society for Cell Biology American Society for Microbiology American Society for Pharmacology and Experimental Therapeutics Honors 1983, 1984 Sea Grant College Program, Undergraduate Research Award 1990-1993 Post-doctoral Fellow of the Damon Runyon-Walter Winchell Cancer Research Fund 1996-1999 Junior Faculty Research Award from the American Cancer Society 1997-2000 Sinsheimer Scholar Award 2006, 2007 Appreciation Award from the Joint Molecular Biosciences Graduate Student Association 2007 Selected to Membership in the Stuart D. Cook Master Educators Guild of UMDNJ 2008 Elected as Fellow of the American Association for the Advancement of Science Extramural Professional Contributions Since 1994 Reviewer of Grant Applications for:

North Carolina Biotechnology Center, Science and Technology Development Program Austrian Science Foundation, Erwin-Schrödinger Stipendium National Science Foundation (U.S.A.) The Wellcome Trust (U.K.) Dutch Cancer Society

Principal Investigator/Program Director (Last, first, middle): Walworth, Nancy C.

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2002 – 2005 Ad Hoc Member 7 NIH study sections and special panels February 2006-- Permanent Member, NIH CSD, Cell Signaling and Dynamics (now CSRS) Study Section Since 1994 Reviewer of manuscripts for over 20 JournalsSince 2000 Member, Gene Naming Committee for the International Fission Yeast Community 2001-2003 Member, Faculty of 1000 Since 2004 Member, Editorial Board of Science’s STKE, now Science Signaling Since 2008 Member, Editorial Board of the Journal of Biological Chemistry B. Publications Ahmed, S., C. Palermo, S. Wan, and N. C. Walworth. 2004. A novel protein with similarities to Rb binding protein 2 compensates for lack of Chk1 function and affects histone modification in fission yeast. Molecular and Cellular Biology 24(9):3660-3669. Dunaway, S. and N. C. Walworth. 2004. Assaying the DNA Damage Checkpoint in Fission Yeast. Methods 33:260-263. Palermo, C. and N. C. Walworth. 2005. Assaying Cell Cycle Checkpoints: Activity of the Protein Kinase Chk1, in Methods in Molecular Biology, vol. 296: Cell Cycle Protocols. Pages 345-354. T. Humphrey and G. Brooks, eds. Humana Press Inc. Totowa, NJ. Dunaway, S., H. Y. Liu and N. C. Walworth. 2005. Interaction of 14-3-3 protein with Chk1 affects localization and checkpoint function. J. Cell Science 118:39-50. Dul, B. and N. C. Walworth. 2007. The PHD fingers of fission yeast Msc1 exhibit E3 ubiquitin ligase activity. J. Biological Chemistry 282:18397-18406. Palermo, C. and N. C. Walworth. 2007. Yeast as a model for studying cell cycle checkpoints, in Yeast as a Tool in Cancer Research, pages 179-189. J. Heitman and J. L. Nitiss, ed. Springer, Dordrecht, the Netherlands. Ahmed, S., B. Dul, Qiu, X. and N. C. Walworth. 2007. Msc1 acts through histone H2A.Z to promote chromosome stability in fission yeast. Genetics, 177:1487-1497. Palermo, C., Hope, J. C., Freyer, G. A., Rao, H. and N. C. Walworth. 2008. Importance of a C-terminal conserved region of Chk1 for checkpoint function. PLoS ONE 3(1):e1427. C. Research Support Ongoing Research Support “Cell Cycle Checkpoint Control in Response to DNA Damage” Principal Investigator: Nancy C. Walworth, Ph.D. Agency: National Institute of General Medical Sciences (NIH) Type: RO1 (GM53194) Period: August 1, 1995-July 31, 2012 The objective of this project is to investigate the mechanism through which the protein kinase Chk1 mediates cell cycle progression in response to DNA damage in eukaryotic cells. This project aims to characterize Chk1 and identify proteins with which it interacts in order to achieve a more thorough understanding of how the presence of DNA damage is communicated to the cell cycle control machinery. This project is ongoing and is currently in its 14th year of continuous funding from the NIH with support through July of 2012.



NAME Guy Werlen, Ph.D. eRA COMMONS USER NAME GUYW1234

POSITION TITLE Associate Professor (non-tenured, tenure track)



University of Geneva, Geneva, Switzerland M.S. 1989 Biology University of Geneva, Geneva, Switzerland Ph.D. 1994 Cell Biology

University of California, San Diego, CA Post-Doc 1994-1997 Signal transduction/ Immunology

A. Positions and Honors Positions and Employment 1988-1989 Undergrad Research Student, Dept. of Medicine, Univ. Hospital of Geneva, Switzerland. Mentor: Dr Barbara Polla. 1989-1994 Graduate Student, Dept. of Medicine, University of Geneva, Switzerland

Mentors: Drs Daniel Lew and Marc Prentki. 1994-1997 Post-Doctoral Fellow, Dept. of Pharmacology, Univ. of California, San Diego.

Mentor: Dr Michael Karin. 1998-2001 Member, Basel Institute for Immunology, Basel, Switzerland (Semi-independent position equivalent to Instructor/Research Assistant Professor in the US). Mentor: Dr Ed Palmer. 2002-2004 Research Scientist, Dept. of Research, Univ. Hospital of Basel, Switzerland (Semi-

independent position equivalent to Instructor/Research Assistant Professor in the US). Mentor: Dr Ed Palmer. 2005-present Non-tenured, tenure track Associate Professor, Dept. of Cell Biology & Neuroscience, Rutgers University, Piscataway, NJ. Awards and Other Professional Activities/Memberships 1991-1993 Graduate Student Fellowship from the Swiss Cancer Foundation. 1993-1994 Graduate Student Fellowship from the Foundation Dr. Dubois-Ferrière-Dinu Lipatti. 1994-1995 Postdoctoral Fellowship for prospective scientist, Swiss National Science Foundation. 1995 Postdoctoral Stipend from the Swiss Academy of Medical Sciences. 1996-1997 Postdoctoral Fellowship for advanced scientist, Swiss National Science Foundation. 2000-present Peer reviewed for Molecular Immunology, J. of Immunology, J. of Cell Science, Blood, EMBO J. and Oncogene. 2000 Session chairman, EFIS Immunology Conference Tatranské Zruby, Slovakia 2002 Ad hoc Review Panelist, The Netherlands Organization for Scientific Research.

2009 Ad hoc Review Panelist, Canada Foundation for Innovation (Leaders Opportunity Fund). 1991-present Member, Swiss Society for Biochemistry/ Swiss Society for Experimental Biology. 2001-present Member, Swiss Society for Allergy and Immunology. 2002-present Member, American Society for Cell Biology. 2005-present Member, Joint Molecular Bioscience Graduate Education Program of Rutgers/UMDNJ- Robert Wood Johnson Medical School, Piscataway, NJ. 2005-present Member of the Advisory Committee, Analytic Cytometry/Image Analysis Shared Resources,

Rutgers University/CINJ/UMDNJ, Piscataway, NJ. 2007-present Member of the Cancer Institute of New Jersey 2008-present Member of the New Brunswick Faculty Council, Rutgers University, NJ

B. Selected peer-reviewed publications 1. Polla, B.S., Werlen, G., Clerget, M., Pittet, D., Rossier, M.F. & Capponi, A.M. (1989) “1,25-Dihydroxy

vitamin D3 induces responsiveness to the chemotactic peptide f-Met-Leu-Phe in the human monocytic line U937: dissociation between calcium and oxidative metabolic responses.” J Leukoc Biol. 45, 381-8.

2. Slosman, D.O., Costabella, P.M., Roth, M., Werlen, G. & Polla, B.S. (1990) “Bleomycin primes monocytes-macrophages for superoxide production.” Eur Respir J. 3, 772-8.

3. Werlen, G., Belin, D., Conne, B., Roche, E., Lew, D.P. & Prentki, M. (1993) “Intracellular Ca2+ and the

regulation of early response gene expression in HL-60 myeloid leukemia cells”. J Biol Chem. 268, 16596-601.

4. Jacinto, E., Werlen, G. & Karin, M., (1998) “Cooperation between Syk and Rac1 leads to synergistic JNK activation in T lymphocytes”. Immunity 8, 31-41. 5. Werlen, G., Jacinto, E., Xia, Y. & Karin, M., (1998) “Calcineurin preferentially synergizes with PKC-θ to activate JNK and IL-2 promoter in T lymphocytes”. EMBO J. 17, 3101-11.

6. Luo, Z.D., Wang Y., Werlen, G., Camp S, Chien, K.R. & Taylor, P., (1999) “Calcineurin enhances acetylcholinesterase mRNA stability during C2-C12 muscle cell differentiation”. Mol Pharmacol. 56, 886-94.

7. Werlen, G.,* Hausmann, B. & Palmer, E., (2000) “A motif in the αβ T cell receptor controls positive selection by modulating ERK activity”. Nature 406, 422-6 (* G. Werlen, is co-corresponding author). (see also News & Views by T.J., Yun and M.J. Bevan in Nature Immunology 2, 13-14(2001)).

8. Rosette, C., Werlen, G., Daniels, M.A., Holman P.O. Alam , S.M., Travers, P.J., Cascoigne, N.R.J., Palmer, E. & Jameson, S.C., (2001) “The impact of duration versus extent of TCR occupancy on T cell activation: A revision of the kinetic proofreading model”. Immunity, 15, 59-70.

9. Werlen, G.* & Palmer, E., (2002) " The TCR signalosome: a dynamic structure with expanding complexity". Curr Opin Immunol. 14,299-305, Review (* G. Werlen is co-corresponding author).

10. Werlen, G.,* Hausmann, B., Naeher, D. & Palmer, E., (2003) " Signaling life and death in the thymus: timing is everything". Science 299, 1859-63, Review (* G. Werlen is co-corresponding author).

11. Lovatt, M., Filby, A., Parravicini, V., Werlen, G., Palmer, E. & Zamoyska, R., (2006) “Lck regulates the threshold of activation in primary T cells, while both Lck and Fyn contribute to the magnitude of the Extracellular Signal-Related Kinase response”. Mol Cell Biol. 26, 8655-65.

12. Daniels, M.A., Teixiero, E., Gill, J., Hausmann, B., Roubaty, D., Holmberg, K., Werlen, G., Holländer, G., Gascoigne, N.R.J. & Palmer, E. (2006) “Thymic selection threshold defined by compartmentalization of Ras/MAPK signalling”. Nature, 444, 761-65.

13. Werlen, G. (2008) “Thymocyte-fate decisions: bittersweet new flavor”. Blood 112, 7-8.

14. Clarke, R.L., Thiemann, S., Refaeli, Y., Werlen, G. & Potter, T.A. (2009) “A new function for LAT and CD8 during CD8-mediated apoptosis that is independent of TCR signal transduction”. Eur J Immunol 39, 1619-31.

15. Pastorino, S., Renganathan, H., Caliva M., Filbert, E.L., Opoku-Ansah, J., Sulzmaier, F., Gawecka, J.E., Werlen, G. * Shaw, A.S & Ramos, J.W., (2010) “The death effector domain PEA-15 negatively regulates T cell receptor signaling”. FASEB J. article fj.09-144295. Published online March 30, 2010.

16. Chou, P.C., Hovhannisyan, Z., Alabanza, L., Jacinto, E. & Werlen, G. (2010) “ The sequential phosphorylation of LAT’s tyrosine residues control the kinetics of ERK activation during thymocyte differentiation”. Manuscript submitted for review.

17. Chou, P.C., Alabanza, L., Hovhannisyan, Z., Ramos, J.W., Jacinto, E. & Werlen, G. (2010) “ PEA-15 a novel regulator of ERK activity and thymocyte development”. Manuscript in preparation.



NAME Nancy Woychik eRA COMMONS USER NAME (credential, e.g., agency login) woychik




University of Wisconsin-Madison, Madison, WI B.S. 1977-1981 Food Chemistry University of Wisconsin-Madison, Madison, WI M.S. 1982-1984 Microbiology University of Wisconsin-Madison, Madison, WI Ph.D. 1984-1986 Microbiology Whitehead Institute, MIT, Cambridge, MA Postdoctoral 1986-1991 Gene Regulation

A. Positions and Honors April 1991-January 1996 ROCHE INSTITUTE OF MOLECULAR BIOLOGY Assistant Member April 1991-January 1996 COLUMBIA UNIVERSITY Department of Biological Sciences Adjunct Assistant Professor February 1996-June 2001 UMDNJ-ROBERT WOOD JOHNSON MEDICAL SCHOOL Department of Molecular Genetics, Microbiology & Immunology Assistant Professor 1997-present CANCER INSTITUTE OF NEW JERSEY-Member RUTGERS UNIVERSITY-Graduate School Faculty Member July 2001-present Associate Professor NIH Postdoctoral Fellowship 1986-1989 Isermann Family Cancer Research Award, New Jersey Commission on Cancer Research 6/96-7/98 American Cancer Society Junior Faculty Award 7/96-6/97 Editorial Board-Molecular and Cellular Biology 1997- 2008 New Jersey Cancer Research Award for Scientific Excellence 5/09

B. Selected peer-reviewed publications Tan, Q., Linask, K. L., Ebright, R. H. and Woychik, N. A. (2000) Activation mutants in yeast RNA polymerase

II subunit RPB3 provide evidence for a structurally conserved surface required for activation in eukaryotes and bacteria. Genes Dev. 14,339-348

Woychik, N. A. (2000) TA-TAAA!! Transcription unveiled. Trends Biochem. Sci. 25,404 Tan, Q., Li, X., Sadhale, P. P., Miyao, T. and Woychik, N.A. (2000) Multiple mechanisms of suppression

circumvent transcription defects in an RNA polymerase mutant. Mol. Cell. Biol. 20,8124-8133 Woychik, N. A. and Reinberg, D. RNA polymerases: subunits and functional domains. Encyclopedia of Life

Sciences, Nature Publishing Group, London (online textbook at www.els.net) Miyao, T., Barnett, J. D. and Woychik, N. A. (2001) Deletion of the RNA polymerase subunit RPB4 acts as a

global, not stress-specific, shut-off switch for RNA polymerase II transcription at high temperatures. J. Biol. Chem. 276, 46408-46413

Woychik, N. A. and Hampsey, M. (2002) The RNA polymerase II transcription machinery: structure illuminates function. Cell 108, 453-463

Woychik, N. A. (2002) RNA polymerases and the eukaryotic transcription machinery. Encyclopedia of the Human Genome, Nature Publishing Group, London (online textbook at www.ehgonline.net)

Tan, Q., Prysak, M. H. and Woychik, N. A. (2003) Loss of the Rpb4/Rpb7 subcomplex in a mutant form of the Rpb6 subunit shared by RNA polymerases I, II and III. Mol. Cell. Biol. 23,33219-3338

http://www.els.net

http://www.ehgonline.net

Suzuki, M., Zhang, J., Liu, M., Woychik, N. A. and Inouye, M. (2005) The use of an mRNA interferase for single protein production in living cells. Mol. Cell 18,253-261 (highlighted in The Scientist, Chemical Engineering News and Genetic Engineering News)

Suzuki, M., Roy, R., Zheng, H., Woychik, N. A. and Inouye, M. (2006) Bacterial bioreactors for high yield production of recombinant protein. J. Biol. Chem. 281,37559-37565

Liu, M., Zhang, Y., Inouye, M. and Woychik, N. A. (2008) Bacterial Addiction Module Toxin Doc Inhibits Translation Elongation through its Association with the 30S Ribosome. Proc. Natl. Acad. Sci. USA 105,5885-5890

Prysak, M. H., Mozdzierz, C. J., Cook, A. M., Zhang, Y., Inouye, M. and Woychik, N. A. (2009) Bacterial toxin YafQ is an endoribonuclease that associates with the ribosome and blocks translation elongation through sequence-specific and frame-dependent mRNA cleavage. Mol. Microbiol. 71,1071-87

Hurley, J. M. and Woychik, N. A. (2009) Bacterial toxin HigB associates with ribosomes and mediates translation-dependent mRNA cleavage at A-rich sites. J. Biol. Chem. 284,18605-13

C. Research Support Research Projects Ongoing or Completed During the Last 3 Years: Ongoing: "Structural Genomics of Eukaryotic Domain Families" Principal Investigator: Gaetano Montelione-Rutgers University Subproject Principal Investigator: Masayori Inouye; Co-PI Nancy Woychik Agency: NIH/NIGMS Type: U54 Specialized Center Grant Period: 07/01/05 - 06/30/10 "Structural Genomics of Membrane Proteins" Principal Investigator: Wayne Hendrickson-Columbia University College of Physicians & Surgeons Subproject Principal Investigator: Masayori Inouye; Co-PI Nancy Woychik Agency: NIH/NIGMS Type: U54 Specialized Center Grant Period: 07/01/05 - 06/30/10 "Single Protein Production in Yeast Cells" Principal Investigator: Nancy Woychik; Co-PI Masayori Inouye Agency: NIH/NIGMS Type: RO1 Period: 9/01/06 - 8/31/10 [no cost extension] "Single Protein Production in Yeast Cells" Principal Investigator: Nancy Woychik Agency: NIH/NIGMS Type: ARRA Award Period: 9/30/09 - 8/31/10 To extend the studies of the parent RO1 to adapt the expression method for membrane protein expression based on the principals of the original proposal "Functional dissection of toxin-antitoxin systems in Mycobacterium tuberculosis" Principal Investigator: Nancy Woychik; Co-PI Robert Husson Agency: NIH/NIAID Type: R21 Period: 7/1/09 - 6/30/11 Investigates of the function of the nine MazF toxin proteins in Mycobacterium tuberculosis





NAME YOUNG, Lily Y. eRA COMMONS USER NAME

POSITION TITLE Professor II, Microbiology Chair Department of Environmental Sciences



Cornell University, Ithaca, NY B.S. 1965 Bacteriology Cornell University, Ithaca, NY M.S. 1967 Bacteriology Harvard University, Cambridge, MA Ph.D. 1972 Environmental Microbiol. A. Positions and Honors Positions and Employment 1969-71 Teaching fellow, Environmental Sciences, Harvard University, Cambridge, MA 1972-80 Assistant Professor, Environ. Engineering, Dept. Civil Engineering, Stanford Univ, Stanford,

CA 1976 Visiting researcher, Scripps Institution of Oceanography, La Jolla, CA 1973, 77, 78 Summer researcher, Marine Biological Laboratory, Woods Hole, MA 1979-90 Research Assoc. Professor, NYU Medical Center, Dept. Environ. Medicine & Microbiol. NY,

NY 1990-92 Research Professor, NYU Medical Center, Dept. Environ. Med. & Microbiology, NY, NY 1992-98 Professor, Biotechnology Center & Dept. Environ. Sciences, Rutgers Univ, New Brunswick,

NJ 1998-2003 Associate Dean of Graduate Programs, Cook College, Rutgers Univ, New Brunswick, NJ 1998- Professor II, Biotech Center & Dept. Environ. Sciences, Rutgers Univ, New Brunswick, NJ 2001-08 Chair, Department of Environmental Sciences, Rutgers Univ, New Brunswick, NJ 2008- Dean of International Programs, School of Environmental and Biological Sciences, Rutgers Other Experience and Professional Memberships (selected) 1972- Member, American Society for Microbiology (ASM) 1985-91 National Science Foundation, Advisory Committee, Division of Bioengin. & Environ. Systems 1987-93 Editorial Board, Applied & Environmental Microbiology, ASM 1988-92 Editorial Board, Microbial Ecology 1992-93 Chair and Organizer, Biodegradation, its Role in Reducing Toxicity and Exposure to

Environmental Contaminants, NIEHS, April 1993. 1993-97 NAS/National Research Council, Committee on contaminated marine sediments 1994-97 FDA, Scientific Advisory Board-National Center for Toxicology Research, Little Rock, AR 1994-96 NAS/NRC Committee on shipboard waste 1995- Steering committee, US-EC Task Force on Environmental Biotechnology 1995-97 NAS/NRC Water Sc. and Technol. Bd, Comm., Research Opportunities and Priorities for the

EPA 1996-2002 ASM, Chairperson of Committee for National and International Awards 1997-99 Editorial Board, Biodegradation 1997-99 Co-Chair, then Chair, Gordon Research Conference on Applied and Environmental

Microbiology 1999 NAS/NRC Biology and Ocean Studies Board Workshop on Marine Biotechnology 1998 US Chair, International Symposium on Application of Biotechnology in the Oil Industry,

Venezuela National Commission on Biotechnology, Caracas

Principal Investigator/Program Director (Last, First, Middle): Young, Lily Y.


1999-06 Scientific Advisory Board, Strategic Environmental Res. and Devel. Program, Dept. of Defense

2000-06 ASM Public and Scientific Affairs Board Environmental Committee 2010- ASM Audit Committee Honors, Citations and Awards 1992 Fellow of the American Academy of Microbiology 1994 Fellow of the American Association for the Advancement of Science 1994 Evans, Mang, & Young, 1991. Appl Environ Microbiol 57:450-454. Noted as one of the 10 most

highly cited papers in the field of Ecology and Environmental Sciences in THE SCIENTIST, Nov 28, 1994.

1999 Research Excellence Award, Cook College, NJ Agric. Exper. Station. Rutgers University 2001 Research Excellence Award, Board of Trustees, Rutgers University 2002 ASM, Proctor and Gamble Award in Applied and Environmental Microbiology 2004 Frank H. Parker Distinguished Lectureship, Dept. Civil and Environmental Engineering, Vanderbilt

University, Nashville TN B. Selected peer-reviewed publication (from more than 100)

Evans PJ, DT Mang, & LY Young. 1991. Anaerobic degradation of toluene by a denitrifying bacterium. Appl Environ Microbiol 57:1139-1145.

Evans PJ, W Ling, NJ Palleroni & LY Young. 1992 Quantification of denitrification by strain T1 during anaerobic degradation of toluene. Appl Microbiol Biotechnol 37:136-140.

Evans PJ, W Ling, B Goldschmidt, ER Ritter & LY Young. 1992. Metabolites formed during anaerobic transformation of toluene and o-xylene and their proposed relationship to the initial steps of toluene mineralization. Appl Environ Microbiol 58:496-501.

Frazer AC, PW Coschigano, LY Young. 1995 Toluene metabolism under anaerobic conditions: a review. Anaerobe 1:293-303.

Kazumi J, ME Caldwell, JM Suflita, DR Lovley & LY Young. 1997 Anaerobic degradation of benzene in diverse environments. Environ Sci Technol 31:813-818.

Zhang X & LY Young. 1997. Carboxylation as an initial reaction in the metabolism of naphthalene and phenanthrene by sulfidogenic consortia. Appl Env Microbiol 63:4769-4764.

Coschigano PW, TS Wehrman & LY Young. 1998. Identification and analysis of genes involved in anaerobic toluene metabolism by strain T1: Putative role of a glycine free radical. Appl Environ Microbiol 64:1650-1656.

Song B, LY Young & NJ Palleroni. 1998. Identification of denitrifier strain T1 as Thauera aromatica and proposal for emendation of the genus Thauera definition. Internat J Systematic Bacteriol 48:889-894.

Phelps CD, LJ Kerkhof & LY Young. 1998. Molecular characterization of a sulfate-reducing consortium which mineralizes benzene. FEMS Microbiol Ecol. 27:269-279.

So CM & LY Young. 1999. Anaerobic degradation of alkanes by a sulfate-reducing bacterium: isolation and characterization. Appl Environ Microbiol 65:2969-2976.

So CM & LY Young. 1999. Initial reactions for anaerobic alkane degradation by the sulfate reducer strain AK-01. Appl Environ Microbiol 65:5532-5540.

Zhang X, ER Sullivan & LY Young. 2001. Aromatic ring reduction in the biodegradation of carboxylated naphthalene by a sulfate reducing consortium. Biodegradation 11:117-124.

So CM & LY Young. 2001. Anaerobic alkane degradation by enriched consortia under four different reducing conditions. Environ Toxicol Chem 20:473-478.

Sullivan ER, C Phelps & LY Young. 2001 Anaerobic mineralization of stable isotope labeled 2-



methylnaphthalene. Appl. & Env. Microbiol. Vol. 67 No. 9: 4353-4357.

Perez-Jimenez JR, LY Young & LJ Kerkhof. 2001 Molecular characterization of sulfate-reducing bacteria in anaerobic hydrocarbon degrading consortia and pure cultures using the dissimilatory sulfite reductase (dsrAB) genes. FEMS Microbiol Ecol 35:145-150.

Phelps CD, X Zhang & LY Young. 2001. Use of stable isotopes to identify benzoate as a metabolite of benzene degradation in a sulfidogenic consortium. Environ Microbiol 3:600-603.

Phelps CD, J Battistelli & LY Young. 2002. Metabolic biomarkers for monitoring anaerobic naphthalene biodegradation in situ. Environ Microbiol 4:532-537.

Shor LM, W Liang, KJ Rockne, LY Young, GL Taghon & DS Kosson. 2003. Intra-aggregate mass transport-limited bioavailability of polycyclic aromatic hydrocarbons to Mycobacterium strain PC01. Environ Sci Technol 37:1545-1552.

Fava F, LY Young, G Zannaroli. 2003. Microbial reductive dechlorination of pre-existing PCBs and spiked 2,3,4,5,6-pentachlorobiphenyl in anaerobic slurries of a contaminated sediment of Venice Lagoon (Italy). FEMS Microbiology Ecology 44:309-318.

So CM, CD Phelps, LY Young. 2003 Anaerobic transformation of alkanes to fatty acids by the sulfate-reducing bacterium, strain Hxd3. Appl & Environ Microbiol 69:3892-3900.

Liu A, E Garcia-Dominguez, ED Rhine & LY Young. 2004 Arsenate reduction coupled to the degradation of aromatic compounds by a new anaerobic isolate. FEMS Microbiol Ecol 48:323-332.

Kim HS, PR Jaffe & LY Young. 2004. Simulating biodegradation of toluene in sand-column experiments at the macroscopic and pore-level scale for aerobic and denitrifying conditions. Adv Water Res 27:335-348.

Young LY & CD Phelps. 2005. Metabolic biomarkers for monitoring in situ anaerobic hydrocarbon degradation. Environ Health Perspectives 113:62-67.

Fedi S, V Tremaroli, D Scala, JR Perez-Jimenez, F. Fava, LY Young & D Zannoni. 2005. T-RFLP analysis of bacterial communities in cyclodextrin-amended bioreactors developed for biodegradation of polychlorinated biphenyls. Res Microbiol 156:201-210.

Gallagher E, L McGuinness, CD Phelps, LY Young & LJ Kerkhof. 2005. 13C-carrier DNA shortens the incubation time needed to detect benzoate-utilizing denitrifying bacteria by stable-isotope probing. Appl Environ Microbiol 71:5192-5196.

Perez-Jimenez JR, CD DeFraia, LY Young. 2005. Arsenate respiratory reductase (ArrA) for Strain Y5. Biochem Biophys Res Comm 338:825-829.

Rhine ED, E Garcia-Dominguez & LY Young. 2005. Environmental microorganisms can speciate and cycle arsenic. Environ Science & Technol 39:9569-9573.

Rhine ED, CD Phelps & LY Young. 2006. Anaerobic oxidation of arsenite oxidation by novel denitrifying isolates. Environ Microbiol 8:899-908, doi:10.1111/j.1462-2920.2005.00977.x

Callaghan, AV, LM Gieg, KG Kropp, JM Suflita & LY Young. 2006. A comparison of alkane metabolism under sulfate-reducing conditions among two isolates and a bacterial consortium. Appl Environ Microbiol 72:4274-4282.

Scala DJ, E Hacherl, R Cowan, LY Young & DS Kosson. 2006. Characterization of Fe(III)-reducing enrichment cultures and isolation of Fe(III)-reducing bacteria from the Savannah River site, South Carolina. Res Microbiol (in press) doi:10.1016/j.resmic.2006.04.001.

Rhine ED, SM Ni Chadhain, GJ Zylstra & LY Young. 2007. The arsenite oxidase genes (aroAB) in novel chemoautotrophic arsenite oxidizers. Biochem Biophys Res Comm (in press).

Rhine ED, KM Onesios, ME Serfes, JR Reinfelder & LY Young. 2008. Arsenic mobilization and transformation from minerals by strain WAO. Environ Sci Technol 42:1423-1429,



Callaghan AV, B Wawrik, SM NiChadhain, LY Young & GJ Zylstra. 2008. Anaerobic alkane degrading strain AK-01 contains two alkylsuccinate synthase genes. Biochem Biophys Res Comm 366(1):142-148.

Oka A, CD Phelps, LM McGuinness, A Mumford, LY Young & LJ Kerkhof. 2008. Identification of critical members in a sulfidogenic benzene-degrading consortium by DNA stable isotope probing. Appl Environ Microbiol 74:6476-6480.

Callaghan AV, M Tierney, CD Phelps & LY Young. 2009. Anaerobic biodegradation of hexadecane by a nitrate reducing consortium. Appl Environ Microbiol 75:1339-1344.

C. Research Support Ongoing Research Support NSF EAR-0433488 Reinfelder (PI) 11/15/04-10/31/08 (no cost extension for 1 yr) Microbial Arsenic Mobilization from Newark Basin Shale This study examines the microbial activity on arsenic bearing minerals in groundwater systems. Role: Co-PI DOE Barkay (PI) 1/05-12/08 Microbial Pathways for the Mobilization of Mercury as Hg(0) in Anoxic Subsurface Environments. This study examines the anaerobic mechanism of mercury reduction and the genes involved. Role: Co-investigator Completed Research Support (within last 5 years) NSF OCE-0120453 Taghon (PI) 10/01-9/05 Biocomplexity: The roles of Resources, Competition and Predation in Microbial Degradation of Organic Matter This is also a multi-investigator grant where our part is studying bacterial competition for nutrient sources in continuous culture studies. Role: Co-PI 5 P42 ES10344 Costa (PI) 4/1/00-3/31/06 (no cost extension) NIEHS Genetic/Epigenetic Susceptibility to Superfund Chemicals The project examines microbial reduction and oxidation of arsenic species found in the environment with relationship to their fate and transport. Role: Project leader NSF CHE-0221978 Morel (PI) 10/02-9/07 (no cost extension) Center for Environmental BioInorganic Chemistry (CEBIC) This is a multi-investigator grant where I am examining the mechanism(s) of anaerobic hydrocarbon biodegradation using molecular biology and proteomics to target the genes and enzymes involved. Role: Project leader ONR N00014-03-1-0572 Young (PI) 10/02-9/06 (no cost extension) Anaerobic Microbial Transformations and Characterization of Microbial Communities Relevant to Nitroaromatic Compounds in Estuarine and Marine Sediments The study investigates pathways for trinitrotoluene degradation and novel microbes in anoxic marine sediments. Role: PI

Principal Investigator/Program Director (Last, First, Middle): YURCHENCO, Peter Dana




NAME Peter Dana YURCHENCO eRA COMMONS USER NAME yurchenco

POSITION TITLE Professor of Pathology and Laboratory Medicine



Wesleyan University, Middletown, CT. B.A. 1970 Biology (magna cum laude)

Albert Einstein College of Medicine, Bronx, NY. Ph.D. 1975 Biochemistry/ Cell biology

Albert Einstein College of Medicine, Bronx, NY. M.D. 1976 Medicine

Please refer to the application instructions in order to complete sections A, B, and C of the Biographical Sketch. A. Research and Professional Experience: 1976-1977: Internship in Medicine, Dartmouth Medical School associated hospitals. 1977-1981: Residency in Pathology, Yale University School of Medicine. Research Fellowship; Advisor: Dr. Vincent T. Marchesi. (Spectrin synthesis; immunologic domain structure of spectrin). 1982-1984: Post-doctoral fellowship, Dept. Pathology, Yale University School of Medicine. Advisor: Dr. Heinz Furthmayr. (“Contribution of non-covalent associations to basement membrane organization"). 1984-1991: Assistant Professor of Pathology & Laboratory Medicine, Robert Wood Johnson Medical School. 1985- : Faculty member of the Biochemistry (1985), Cell and Developmental (1987), Microbiology (1990) and Molecular Biosciences Graduate Programs of Rutgers University. 1991-1997: Associate Professor with tenure, Department of Pathology & Laboratory Medicine. Robert Wood Johnson Medical School. 1995- : Chief, Division of Experimental Pathology, Robert Wood Johnson Medical School. 1997- : Professor of Pathology & Laboratory Medicine, Robert Wood Johnson Medical School. 2000- : Vice-Chairman, Department of Pathology & Laboratory Medicine, Robert Wood Johnson Medical School Honors: 1985-1988: Sinsheimer Scholar. 1986-1989: John A. Hartford Foundation Fellow. 1995: Chairman, 15th Annual East Coast Connective Tissue Society Meeting. 1996, 1998: Vice-Chairman (1996) and Chairman (2000) of Basement Membrane Gordon Conference 1996-2000: Regular Member, Pathobiochemistry Study Section (N.I.H.). 2003: Selected for NIH MERIT status (R01-DK36425) B. Publications (selected): Tsiper, M. and P.D. Yurchenco. (2002). Laminin assembles into separate basement membrane and fibrillar matrices in Schwann cells. J. Cell Sci. 115: 1005-1015. Smirnov, S., E. McDearmon, S. Li, J. Ervasti, K. Tryggvason and P.D.Yurchenco (2002). Contributions of the LG modules and furin-processing to laminin-2 functions. J. Biol. Chem. 277: 18928-18937. Li, S., D. Harrison, S. Carbonetto, R. Fässler, N. Smyth, D. Edgar and P.D. Yurchenco (2002). Matrix

Principal Investigator/Program Director (Last, First, Middle): YURCHENCO, Peter Dana

PHS 398/2590 (Rev. 09/04, Reissued 4/2006) Page __ Continuation Format Page

assembly, regulation and survival functions of laminin and its receptors in embryonic stem cell differentiation. J. Cell Biol. 157: 1279-1290. Rybakova IN, Patel JR, Davies KE, Yurchenco PD, Ervasti JM. (2002). Utrophin binds laterally along actin filaments and can couple costameric actin with sarcolemma when overexpressed in dystrophin-deficient muscle. Mol Biol Cell 3: 1512-21. Sakai, T., S. Li, D. Docheva, C. Grashoff, K. Sakai, G. Kostka, A. Braun, A. Pfeifer, P.D. Yurchenco, and R. Fässler. 2003. Integrin-linked kinase (ILK) is required for polarizing the epiblast, cell adhesion, and controlling actin accumulation. Genes Dev. 17: 926-940. Li, S., D. Edgar, R. Fässler, W. Wadsworth, and P.D. Yurchenco. 2003. The role of laminin in embryonic cell polarization and tissue organization. Dev Cell. 4: 613-624. Yurchenco, P.D., Y.S. Cheng, K. Campbell, and S. Li. 2004. Loss of basement membrane, receptor and cytoskeletal lattices in a laminin-deficient muscular dystrophy. J Cell Sci. 117 :735-42. Yurchenco, P.D., P.S. Amenta, and B.L. Patton. 2004. Basement membrane assembly, stability and activities observed through a developmental lens. Matrix Biol. 22: 521-38. Miner, J.H., and P.D. Yurchenco. 2004. Laminin functions in tissue morphogenesis. Annu Rev Cell Dev Biol. 20: 255-284. Li, S., P. Liquari, K.K. McKee, D. Harrison, R. Patel, S. Lee, and P.D. Yurchenco. 2005. Laminin-sulfatide binding initiates basement membrane assembly and enables receptor signaling in Schwann cells and fibroblasts. J Cell Biol. 169:179-89. Li, S., R. Bordoy, F. Stanchi, M. Moser, A. Braun, O. Kudlacek, U.M. Wewer, P.D. Yurchenco, and R. Fassler. 2005. PINCH1 regulates cell-matrix and cell-cell adhesions, cell polarity and cell survival during the peri-implantation stage. J Cell Sci. 118:2913-21. Smirnov, S.P., P. Barzaghi, K.K. McKee, M.A. Ruegg, and P.D. Yurchenco. 2005. Conjugation of LG domains of agrins and perlecan to polymerizing laminin-2 promotes acetylcholine receptor clustering. J Biol Chem. 280: 41449-57. Harrison, D., S.A. Hussain, A.C. Combs, J.M. Ervasti, P.D. Yurchenco. 2007. Crystal structure and cell surface anchorage sites of laminin alpha1LG4-5. J. Biol. Chem. 282: 11573-81. Colognato, H., J. Galvin, J. Relucio, T. Nguyen, D. Harrison, P.D. Yurchenco, C. fFrench-Constant. 2007. Identification of dystroglycan as a second laminin receptor in oligodendrocytes, with a role in myelination. Development 134: 1723-36. Myers, J.C., P.S. Amenta, A.S. Dion, J.P. Sciancalepore, C. Nagaswami, J.W. Weisel, P.D. Yurchenco. 2007. The molecular structure of human tissue type XV collagen presents a unique conformation among the collagens. Biochem. J. 404: 535-544. McKee, K.M., Harrison, D., Capizzi, S. and Yurchenco, P.D. 2007. Contributions of the LN and nidogen-binding

domains of laminin-111 to self-assembly and basement membrane formation. J. Biol. Chem.,282: 21437-21447.

Wu, X., Li, S., Chrostek-Grashoff, A., Myer, H., Yurchenco, P.D., Brakebusch, C. 2007. Cdc42 is crucial for the establishment of epithelial polarity during early mammalian development. Dev. Dyn. 236: 2767 - 2778.

McKee, K.K., Capizzi, S., and Yurchenco, P.D. 2009. Scaffold-forming and adhesive contributions of synthetic laminin-binding proteins to basement membrane assembly. J. Biol. Chem.284: 8984 - 8994.

Yurchenco, P.D. and B.L. Patton. 2009. Developmental and pathogenic mechanisms of basement membrane assembly. Curr. Pharmaceutical Design. 15: 1277-1294.

C. RESEARCH SUPPORT N.I.H., R37-DK36425 (MERIT AWARD). Role in project: P.I.: Project dates: 1/1/1986 - 12/31/2011. Title: Basement Membrane Self-assembly and Structure. Goals: To understand how basement membranes self-assemble into a three-dimensional architecture and affect cell functions. Total costs for year 24: $278,082 (direct costs: $178,258). NIH, R01-NS38469. Role in project: P.I. Project dates: 4/1/1999 - 6/30/2010. Title: Laminin-induced Membrane Complexes in Muscle and Nerve. Role in project: P.I. Goals: to study the membrane-cytoskeletal inductive roles of laminin-2 in muscle and peripheral nerve. No cost extension for year 11.



NAME Helmut Zarbl eRA COMMONS USER NAME hzarbl

POSITION TITLE Professor of Environmental and Occupational Medicine



Marianopolis College, Montreal, Canada D.C.S 1973-1975 Health Sciences

McGill University, Montreal, Canada B.Sc. 1975-1978 Biochemistry

McGill University, Montreal, Canada Ph.D. 1978-1983 Biochemistry NIH - Frederick Cancer Research Facility, MD Post-doc 1983-1985 Molecular Biology Clinical Research Institute of Montreal, Canada Post-doc 1985-1987 Cancer Genetics

A. Personal Statement Dr. Helmut Zarbl brings substantial administrative leadership and research experience to the Advisory Committee. He is a Professor in the Department of Environmental and Occupational Medicine at the Robert Wood Johnson Medical School (RWJMS), University of Medicine and Dentistry of New Jersey (UMDNJ). He is a Member of the Environmental and Occupational Health Sciences Institute, jointly sponsored by UMDNJ-RWJMS and Rutgers, The State University of New Jersey. Dr. Zarbl also serves as the Director of the NIEHS Core Center for Environmental Exposure and Disease at UMDNJ-Rutgers. Dr. Zarbl serves on numerous national research review and advisory panels, including the National Academy of Sciences’ National Research Council Committee on the Applications of Toxicogenomics to Predictive Toxicology. He was also the Director of NIEHS sponsored Fred Hutchinson Cancer Research Center/University of Washington Toxicogenomics Consortium, serving as the Chair of the Steering Committee for the National Institute of Environmental Health Sciences National Toxicogenomics Consortium for two years. Dr. Zarbl has been continuously funded by NIH since beginning his career in 1987. In 2005, Dr. Zarbl was the co-recipient of received U.S. Patent No. 6,939,712 entitled “Muting Gene Activity Using a Transgenic Nucleic Acid, which includes the earliest disclosure of postranscriptional gene silencing ( or RNAi) in 1994. Dr. Zarbl’s research has focused largely on toxicogenomics and functional genomics, carcinogenesis, molecular and cellular biology, and toxicology. Specifically this has included work understand to molecular mechanisms of chemical carcinogenesis and the genetic basis for differential susceptibility to mammary carcinogenesis using both animal and in vitro model systems. Studies in the rat model have included analysis of oncogene activation, mechanisms of signal transduction, and genetic linkage analysis to identify mammary tumor suppressor genes. He has also used toxicogenomics to dissect mechanisms of mechanism carcinogenesis, tumor progression and chemoprevention. His studies in the area of toxicogenomics include the development and application of standards for DNA microarray experiments, and phenotypic anchoring of response of human cells, model organisms (yeast) and target organs (rodents) to toxicants, providing insights into dose and temporal responses, as well as mechanisms of action. He is also actively involved in technology development. B. Professional Positions and Honors

Positions and Employment 1987-1992 Assistant Professor, Department Applied Biological Sciences, Massachusetts Institute of Technology, Cambridge, MA 1992-1994 Associate Professor, Division of Toxicology, Whitaker College of Health Sciences and

Technology Massachusetts Institute of Technology, Cambridge, MA 1994-2006 Member, Divisions of Human Biology & Public Health Sciences, Fred Hutchinson Cancer

Research Center (FHCRC), Seattle, WA 1995- 2006 Member, Center for Ecogenetics and Environmental Health, UW, Seattle, WA

1996-2006 Affiliate Professor, Departments of Environmental and Occupational Health & Pathology, University of Washington, Seattle, WA

1998-2002 Scientific Director, DNA Microarray Shared Resource, FHCRC, Seattle, WA 1998-2002 Director, Public Health Sciences Core Laboratory, FHCRC, Seattle, WA 2002-2004 Director, Industrial Liaison Program, FHCRC, Seattle, WA 2000-2006 Director, NIEHS - FHCRC/UW Toxicogenomics Research Consortium, Seattle, WA 2000- Visiting Professor of Genetics, China Medical University, Shenyang, China 2006- Professor, Environmental and Occupational Medicine, Robert Wood Johnson Medical

School, Environmental and Occupational Health Sciences Institute, Piscataway, NJ 2007- Director, UMDNJ/Rutgers NIEHS Center for Environmental Exposures and Disease. 2008- Associate Director, Division of Public Health Sciences. Cancer Institute of New Jersey, New

Brunswick, NJ Honors and Professional Recognition 2010 Vice President (elect), Carcinogenesis Specialty Section, Society for Toxicology 2009- Member, National Academy of Sciences, National Research Council Standing Committee on

“Emerging Science for Environmental Health Decisions” 2009- NIEHS Superfund Basic Research Program, External Advisory Panel 2009- External Scientific Advisory Board Superfund Basic Research Program University of North

Carolina. Chapel Hill, NC 2008- Fellow of the Academy of Toxicological Sciences 2008 - 2010 Chair, Disease Prevention Task Force, Society of Toxicology 2008 EPA-IRIS Peer Review Panel: Toxicological Review of 1,2,3-Trichlropropane 2008 NIEHS Superfund Basic Research Program External Advisory Board 2006 - 2008 Editor-In Chief, Biological Procedures Online 2002 – 2004 Associate Editor, Environmental Health Perspectives: Toxicogenomics 2000 – 2002 Associate Editor, Cancer Research (AACR) 1999- Chair, External Scientific Advisory Board Member, Research Center for

Minority Institutions, Clark Atlanta University, Atlanta, GA 1993-1994 Associate Director, M.I.T. Center for Environmental Health Sciences 1988-1989 Robert A. Swanson Assistant Professor of Life Sciences.

C. Selected Peer-reviwed Publications

1. Zarbl, H., Sukumar, S., Arthur, A.V., Martin-Zanca, D., and Barbacid, M. Direct mutagenesis of Ha-ras-1 oncogenes by N-nitroso-N-methylurea during initiation of mammary carcinogenesis in rats. Nature 315:382-385. 1985.

2. Zarbl, H., Latreille, J. and Jolicoeur, P. Revertants of v-fos transformed fibroblast have mutations in cellular genes essential for transformation by other oncogenes. Cell 51:357-369. 1987.

3. Kho, C.-J. and Zarbl, H. Fte-1, a Fos-transformation effector gene, encodes the mammalian homologue of a yeast gene involved in protein import into mitochondria. Proc. Natl. Acad. Sci. USA, 89:2200-2204. 1991.

4. Cha, R.S., Thilly, W.G. and Zarbl, H. NMU induced mammary tumors arise from cells with pre-existing oncogenic Ha-ras-1 gene mutations. Proc. Natl. Acad. Sci. USA 91:3749-3753, 1994.

5. Jin, Z., Houle, B., Mikheev, A.M., Cha, R.S. and Zarbl, H. Alterations in Hras1 promoter topology during NMU-induced mammary carcinogenesis and pregnancy. Cancer Research 56:4927-35, 1996.

6. Bahramian, M.B. and Zarbl, H. Transcriptional and Posttranscriptional Silencing of Rodent α1(I) Collagen by a Homologous Transcriptionally Self-Silenced Transgene. Mol.Cell. Biol.19:274-283, 1999.

7. Mikheev, A. M., Mikheeva, S A., Zhang, Y., Aebersold, R., and Zarbl, H. CArG Binding Factor A (CBF-A) is Involved in Transcriptional Regulation of the Rat Ha-ras Promoter. Nucleic Acids Res. 28(19): 3762-3770, 2000.

8. Mikheev, A.M., Mikheeva S.A., Liu, B., Cohen, P. and Zarbl, H. A functional genomics approach for identification of putative tumor suppressor genes: Insulin Growth Factor Binding Protein-3 and Dickkopf-1 as suppressors of HeLa cell transformation. Carcinogenesis 24 (10): 1-13, 2003.

9. Luo, W., Fan, W., Xie, H., Jing, L., Ricicki, E., Vouros, P, Zhao, L.P., and Zarbl, H. Phenotypic Anchoring of Global Gene Expression Profiles Induced by N-hydroxy-4-acetylaminobiphenyl and Benzo(a)pyrene diol epoxide Reveals Correlations Between Expression Profiles and Mechanism of Toxicity. Chemical Research in Toxicology 18(4): 619-629, 2005.

10. Bammler, T., R.P. Beyer, S. Bhattacharya, G. Boorman, A. Boyles, B.U. Bradford, R.E. Bumgarner, P.R. Bushel, D. Choi, M. Cunningham, S. Deng, H.K. Dressman, R.D. Fannin, F.M. Farin, J.H. Freedman, R.C. Fry, M.C., Humble, P. Hurban, L. Jing, T.J. Kavanagh W.K. Kaufmann, K.F. Kerr, S. Milton, J.A. Lapidus, M. Lasarev, J. Li, Y.-J. Li E.K. Lobenhofer, X. Lu, R.L. Malek, S. Milton, S. Nagalla, J.P. O’Malley, V.S. Palmer, P. Pattee, R.S. Paules, C.M. Perou, L. Qin, S.D. Quigley, M. Rodland, I. Rusyn, L.D. Samson, D.A. Schwartz, Y. Shi, J.-L. Shin, S.O. Sieber, S. Slifer, M.C. Speer, P.S. Spencer, D.I. Sproles, W.A. Suk, R.C. Sullivan, J. Swenberg, R. Tennant, R. Tian, S.A. Todd, C.J. Tucker, B. van Houten, B.K. Weis, H. Zarbl. Standardizing Global Gene Expression Analysis Between Laboratories and Across Platforms. Nature Methods 2, 351 – 356, 2005.

11. Guo, Y., Breeden, L. L., Kelley, E., and Eaton, D. L., and Zarbl, H. Analysis of Cellular Responses to Aflatoxin B1 in Yeast Expressing Human Cytochrome P450 1A2 using cDNA Microarrays. Mutation Research 593:121-142, 2006.

12. Beyer, R.P., Fry, R.C., Lasarev, M.R., McConnachie, L.A., Meira, L.B., Palmer, V., PowellC.L., Ross, P.K., Bammler, T.K., Bradford, B.U., Cranson, A.B., Cunningham, M.L., Fannin, R.D., Higgins, G.M., Hurban, P., Kayton, R.J., Kerr, K.F., Kosyk, O., Lobenhofer, E.K., Sieber, S.O., Vliet, P.A., Weis, B.K., Wolfinger, R., Woods, C.G., Freedman, J.H., Linney, E., Kaufmann, W.K., Kavanagh, T.J., Paules, R.S., Rusyn, I., Samson, L.D., Spencer, P., Suk, W., Tennant, R.J., Zarbl, H Multi-center study of acetaminophen hepatotoxicity reveals the importance of biological endpoints in genomic analyses. Toxicological Sciences 99(1):326-337, 2007.

13. Ren, X., Zhang, X., Kim, A. S., Mikheev, A. M., Fang, M., Sullivan, R. Bumgarner, R., Zarbl, H. Comparative Genomics of Susceptibility to Mammary Carcinogenesis among Inbred Rat Strains: Role of Reduced Prolactin Signaling in Resistance of the Copenhagen Strain. Carcinogenesis 29(1): 177-185 2007. ePub 2007/10/06

14. Zhang, X and Zarbl, H. Chemopreventive Doses of Methylselenocysteine Alter Circadian Rhythm in Rat Mammary Tissue but Not Liver. Cancer Prevention Research 2(1):119-127, 2008.

15. Ming Zhu Fang, Xun Zhang and Helmut Zarbl. (2010). Methylselenocysteine Inhibits Carcinogenesis by Enhancing Circadian Expression of Melatonin Receptor 1α and Estrogen Receptor β in Rat Mammary Epithelial Cells. Cancer Prevention Research, In Press.

D. Research Support. Current 1. 5P30 ES005022 (Helmut Zarbl, P.I.) 04/01/2009- 3/31/2014 30% NIH/NIEHS $8,581,519 (total costs) Research Center in Environmental Health Science. The Center for Environmental Exposures and Disease provides core support pilot funding and career development awards to environmentally relevant studies. 2. V Foundation Translational Grant (Helmut Zarbl, Ph.D. , P.I.) 10/01/2008 – 9/31/08/2011 15% The V Foundation for Cancer Research $600,000. ( total cost) Chemoprevention of Breast and Prostate Cancers in Shift Workers by Dietary Methylselenocysteine:Effects on Circadian Rhythm and Estrogen Receptor-β Cycling The proposed studies will confirm that shift work disrupts circadian rhythm normal expression of the ERβ tumor suppressor protein using blood cells. We will then determine if can restore normal rhythm and ERβ expression with a dietary supplement. These results will then form the basis for a long term, prospective intervention trial in a large population of shift workers to determine if Methylselenocysteine can actually prevent breast and prostate cancer in shift workers. 3. 1R01CA112231-01 (Helmut Zarbl, Co-P.I) 12/01/04 – 11/31/011 20% NIH/NCI $2,889,789 (total costs)

Relating DNA Adducts and Toxicogenomics The program goal is to generate an integrated picture illustrating the effects of cell exposure to carcinogens by combining data from cell toxicity, mutation fraction, gene expression, genotype, and DNA adduct analyses. We aim to characterize global gene expression patterns in human cells exposed to carcinogens using DNA microarrays, and phenotypically anchor the transcriptional responses with assays of cell survival, genotypes of xenobiotic metabolizing enzymes, induced mutation frequencies, and DNA adduct levels as measured by capillary LC-MS. Three well characterized carcinogens, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), 4-aminobiphenyl (ABP), benzo[a]pyrene (B[a]P), - all of which have been identified as constituents of cigarette smoke and have been implicated as causative agents in lung cancer, will serve as model compounds for this study. 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), an IARC category 2A carcinogen (probable human carcinogen) that is known to be derived primarily from cooked meats will be used to assess the sensitivity of our program to low level carcinogens that can be found in cigarette smoke, but which have not been directly implicated in lung cancer. 4. 09-1077-CCR-EO Helmut Zarbl, P.I.

06/25/2009-06/25/2011 5% New Jersey Commission on Cancer Research $235,074 (total costs) Effect of Fetal Zearanol Exposure on Adult Disease

The overall goal of this study is to determine the effects of in utero exposure to the food contaminant, zearanol, on breast cancer later in life or in subsequent generations. Although the study of other diseases is not explicitly a goal of the present proposal, the efficient nested study design will generate biological samples that can be used to assess the trans-generational effects of zearanol exposure on fertility, obesity, metabolic and the risk of developing precocious puberty.

5. Developmental Research Grant Helmut Zarbl, Co-P.I. 07/01/09- 07/01/10 5%

Cancer Institute of New Jersey $70,000 Role of CBF-A in Regulation of Epithelial-Mesenchymal Transition and Metastasis The overall goal of the proposed studies is to demonstrate that CArG Box Binding Factor-A (CBF-A), the master regulator of Epithelial-Mesenchymal Transition (EMT), plays a key regulatory role in metastasis. To further investigate the role of CBF-A in normal development processes and carcinogenesis, we generated CBF-A (null/null) knockout mice as well as a conditional CBF-A (flox/flox) knockout strain. The goal of the present proposal is to test this hypothesis in vivo by examining the effect of CBF-A loss on carcinogenesis and metastasis. Recently Completed Research Support U19-ES-011387-01 (Helmut Zarbl, Director and P.I) 09/01/01 – 08/31/07 20% NIH/NCI $7,256,486. (total costs) The FHCRC/UW Toxicogenomics Consortium The mission of the FHCRC/UW Consortium is to participate in the development and validation of standardized methodologies for the application of the emerging technologies of DNA microarrays and proteomics to Toxicology research. To fulfill this mission, the consortium has defined several goals. • The first goal is to provide scientific input to the N.I.E.H.S. Toxicogeneomics Research Consortium (TRC). • The second goal is to develop strong cooperative interactions with other CRMs, the Resource Contractor,

and the NIEHS Staff and Microarray Facility • The third goal is to support the research activities of the four Research Projects proposed by the

FHCRC/UW Consortium. • The fourth goal is to contribute to a public toxicology database provided by the Resource Contractor.

program director/principal investigator (last, first, middle)...

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