jonathan c. schisler, ms, phd - university of north...

6/15/15 Schisler CV 1

Jonathan C. Schisler, MS, PhD

UNC McAllister Heart Institute 121 Hatchet Creek Ct The University of North Carolina Morrisville, NC 27560 Chapel Hill, NC, 27599 919-244-1141 919-843-8708 [email protected] EDUCATION Postdoctoral research fellow 2006 – 2011 McAllister Heart Institute University of North Carolina at Chapel Hill

Postdoctoral research associate 2006 Sarah W. Stedman Nutrition & Metabolism Center Duke University PhD – Biomedical Sciences: Biochemical Regulation and Metabolism 2000 – 2006 University of Texas Southwestern Medical Center MS - Bioengineering 1998 – 2000 College of Engineering University of Toledo Post-baccalaureate research fellow 1997 Argonne National Laboratory US Department of Energy BS, cum laude, Biology 1997 College of Arts and Science Honors Program University of Toledo

PROFESSIONAL EXPERIENCE Assistant Professor, Research Track Department of Pharmacology 2014 – present University of North Carolina at Chapel Hill Research Instructor Department of Pharmacology 2014 Department of Medicine, Division of Cardiology 2011 – 2014 University of North Carolina at Chapel Hill Owner 2010 – present Jumpstart Science Associate Faculty Member 2008 – present Faculty of 1000


HONORS Clinical Loan Repayment Program 2011 – 2015 NIH, National Heart, Lung, and Blood Institute (NHLBI), Early Investigator Career Award 2009 Society for Heart and Vascular Metabolism Postdoctoral Fellowship Award 2008 – 2010 American Heart Association Clinician-Scientist Training Program in Cardiovascular Medicine 2006 – 2008 University of North Carolina at Chapel Hill NIH, National Heart, Lung, and Blood Institute (NHLBI), Symposia Scholarship 2006 Keystone Symposia on Molecular and Cellular Biology Investigator Retreat Scholarship 2004 Beta Cell Biology Consortium Undergraduate Research Fellowship Award, 1997 Argonne National Laboratory Honors in Biology, 1997 Graduate with College Honors, University of Toledo BIBLIOGRAPHY

Book Chapters 1. Stansfield WE, Ranek M, Pendse A, Schisler JC, Wang S, Pulinilkunnil T, Willis MS: Chapter 4:

The Pathophysiology of Cardiac Hypertrophy and Heart Failure, Pages 51-78. In: Willis MS, Homeister, JW, Stone JR, eds. Cellular and Molecular Pathobiology of Cardiovascular Disease. 1st ed. Academic Press, 2014.

Refereed Papers: Original Research 1. Schisler JC, Ronnebaum SM, Madden M, Channell M, Campen M, Willis MS. Endothelial

inflammatory transcriptional responses to an altered plasma exposome following inhalation of diesel emissions. Inhal Toxicol. 5:1-9 (May 2015, PMID: 25942053).

2. Skinner HG, Calancie L, Vu MB, Garcia B, DeMarco M, Ammerman A, Schisler JC. Using Community-Based Participatory Research Principles to Develop More Understandable Recruitment and Informed Consent Documents in Genomic Research. PLoS One. 10(5):e0125466 (May 2015, PMID: 25938669).

3. Schisler JC, Grevengoed BS, Ellis JM, Paul DS, Willis MS, Patterson C, Jia W, Coleman MD. Cardiac energy dependence on glucose increases metabolites related to glutathione and activates metabolic genes controlled by mTOR. JAMA. 4(2) (Feb 2015, PMID: 25713290).

4. Chandler RL, Damrauer JS, Raab, JR, Schisler JC, Wilkerson MD, Didion JP, Starmer, J, Serber D, Yee D, Xiong J, Darr DB, Pardo-Manuel de Villena F, Kim Y, Magnuson T. Coexistent ARID1A-


PIK3CA mutations promote ovarian clear-cell tumorigenesis through pro-tumorigenic inflammatory cytokine signalling. Nat Commun. 6:6118 (Jan 2015, PMID: 25625625).

5. Shi C, *Schisler JC, Rubel CE, Tan S, Song B, McDonough H, Xu L, Portbury A, Mao C, Tru C, Wang R, Wang Q, Sun S, Seminara SB, Patterson C, Xu Y. Ataxia and hypogonadism caused by the loss of ubiquitin ligase activity of the U box protein CHIP. Hum Mol Genet 23, 1013 (Feb 2014; PMID: 24113144).

6. Hayes HL, Moss LG, Schisler JC, Haldeman JM, Zhang Z, Rosenberg PB, Newgard CB, Hohmeier HE. Pdx-1 activates islet alpha- and beta-cell proliferation via a mechanism regulated by transient receptor potential cation channels 3 and 6 and extracellular signal-regulated kinases 1 and 2. Mol Cell Biol 33, 4017 (Oct 2013; PMID: 23938296).

7. Rubel CE, *Schisler JC, Hamlett ED, DeKroon RM, Alzate O, Patterson C. Diggin’ on U(biquitin): A novel method for the identification of physiological E3 ibiquitin-ligase substrates. Cell Biochem Biophys 67, 127 (Sep 2013; PMID: 23695782).

8. Reyskens KM, Fisher TL, Schisler JC, O'Connor WG, Rogers AB, Willis MS, Planesse C, Rondeau P, Bourdon E, Essop MF. The maladaptive effects of HIV protease inhibitors (Lopinavir/Ritonavir) on the rat heart. PLoS ONE 8, e73347 (Sep 2013; PMID: 24098634).

9. Schisler JC, Rubel CE, Zhang C, Lockyer P, Cyr DM, Patterson C. CHIP protects against cardiac pressure overload through regulation of AMPK. J Clin Invest 123, 3588 (Aug 2013; PMID: 23863712).

10. Willis MS, Dyer LA, Ren R, Lockyer P, Moreno-Miralles I, Schisler JC, Patterson C. BMPER regulates cardiomyocyte size and vessel density in vivo. Cardiovascular pathology: the official journal of the Society for Cardiovascular Pathology 22, 228 (May-Jun 2013; PMID: 23200275).

11. Willis MS, Wadosky KW, Rodriguez JE, Schisler JC, Lockyer P, Hilliard EG, Glass DJ, Patterson C. Muscle ring finger 1 and muscle ring finger 2 are necessary but functionally redundant during developmental cardiac growth and regulate E2F1-mediated gene expression in vivo. Cell biochemistry and function, (Mar 2013; PMID: 23512667).

12. Chandler RL, Brennan J, Schisler JC, Serber D, Patterson C, Magnuson T. ARID1a-DNA interactions are required for promoter occupancy by SWI/SNF. Mol Cell Biol 33, 265 (Jan 2013; PMID: 23129809).

13. Pi X, Lockyer P, Dyer LA, Schisler JC, Russell B, Carey S, Sweet DT, Chen Z, Tzima E, Willis MS, Homeister JW, Moser M, Patterson C. Bmper inhibits endothelial expression of inflammatory adhesion molecules and protects against atherosclerosis. Arterioscler Thromb Vasc Biol 32, 2214 (Sep 2012; PMID: 22772758).

14. Stephens SB, Schisler JC, Hohmeier HE, An J, Sun AY, Pitt GS, Newgard CB. A VGF-derived peptide attenuates development of type 2 diabetes via enhancement of islet β-cell survival and function. Cell Metab 16, 33 (Jul 2012; PMID: 22768837).

15. Schisler JC, Charles PC, Parker JS, Hilliard EG, Mapara S, Meredith D, Lineberger RE, Wu SS, Alder BD, Stouffer GA, Patterson C. Stable patterns of gene expression regulating carbohydrate metabolism determined by geographic ancestry. PLoS One 4, e8183 (Dec 2009; PMID: 20016837).

16. Willis MS, Schisler JC, Li L, Rodríguez JE, Hilliard EG, Charles PC, Patterson C. Cardiac muscle ring finger-1 increases susceptibility to heart failure in vivo. Circ Res 105:80 (Jul 2009; PMID: 19498199).

17. Charles PC, Alder BD, Hilliard EG, Schisler JC, Lineberger RE, Parker JS, Mapara S, Wu SS, Portbury A, Patterson C, Stouffer GA. Tobacco use induces anti-apoptotic, proliferative patterns of gene expression in circulating leukocytes of Caucasian males. BMC Med Genomics 1, 38. (Aug 2008; PMID: 18710571).

18. Schisler JC, Fueger PT, Babu DA, Hohmeier HE, Tessem JS, Lu D, Becker TC, Naziruddin B, Levy M, Mirmira RG, Newgard CB. Stimulation of human and rat islet beta-cell proliferation with retention of function by the homeodomain transcription factor Nkx6.1. Mol Cell Biol 28, 3465 (May 2008; PMID: 18347054).


19. Fueger PT, Schisler JC, Lu D, Babu DA, Mirmira RG, Newgard CB, Hohmeier HE. Trefoil factor 3 stimulates human and rodent pancreatic islet beta-cell replication with retention of function. Mol Endocrinol 22, 1251 (May 2008; PMID: 18258687).

20. Raum JC, Gerrish K, Artner I, Henderson E, Guo M, Sussel L, Schisler JC, Newgard CB, Stein R. FoxA2, Nkx2.2, and PDX-1 regulate islet beta-cell-specific mafA expression through conserved sequences located between base pairs -8118 and -7750 upstream from the transcription start site. Mol Cell Biol 26, 5735 (Aug 2006; PMID: 16847327).

21. Artner I, Le Lay J, Hang Y, Elghazi L, Schisler JC, Henderson E, Sosa-Pineda B, Stein R. MafB: an activator of the glucagon gene expressed in developing islet alpha- and beta-cells. Diabetes 55, 297 (Feb 2006; PMID: 16443760).

22. De J, Chang Y-C, Samli KN, Schisler JC, Newgard CB, Johnston SA, Brown KC. Isolation of a mycoplasma-specific binding peptide from an unbiased phage-displayed peptide library. Mol Biosyst 1, 149 (Jul 2005; PMID: 16880978).

23. Schisler JC, Jensen PB, Taylor DG, Becker TC, Knop FK, Takekawa S, German M, Weir GC, Lu D, Mirmira RG, Newgard CB. The Nkx6.1 homeodomain transcription factor suppresses glucagon expression and regulates glucose-stimulated insulin secretion in islet beta cells. Proc Natl Acad Sci U S A 102, 7297 (May 2005; PMID: 15883383).

24. Iype T, Francis J, Garmey JC, Schisler JC, Nesher R, Weir GC, Becker TC, Newgard CB, Griffen SC, Mirmira RG. Mechanism of insulin gene regulation by the pancreatic transcription factor Pdx-1: application of pre-mRNA analysis and chromatin immunoprecipitation to assess formation of functional transcriptional complexes. J Biol Chem 280, 16798 (Apr 2005; PMID: 15743769).

25. Bain JR, *Schisler JC, Takeuchi K, Newgard CB, Becker TC. An adenovirus vector for efficient RNA interference-mediated suppression of target genes in insulinoma cells and pancreatic islets of langerhans. Diabetes 53, 2190 (Sep 2004; PMID: 15331526).

26. Newgard CB, Lu D, Jensen MV, Schisler J, Boucher A, Burgess S, Sherry AD. Stimulus/secretion coupling factors in glucose-stimulated insulin secretion: insights gained from a multidisciplinary approach. Diabetes 51, S389 (Dec 2002; PMID: 12475781).

27. Cheng B, Fournier RL, Relue PA, Schisler J. An experimental and theoretical study of the inhibition of Escherichia coli lac operon gene expression by antigene oligonucleotides. Biotechnol Bioeng 74, 220 (Aug 2001; PMID: 11400095).

* Indicates co-first authorship Refereed Papers: Review Articles 1. Ronnebaum SM, Patterson C, Schisler JC. Emerging evidence of coding mutations in the ubiquitin–

proteasome system associated with cerebellar ataxias. Hum Genome Var 1 (2014). 2. Ronnebaum SM, Patterson C, Schisler JC. Hey U(PS): Metabolic and Proteolytic Homeostasis

Linked via AMPK and the Ubiquitin Proteasome System. Mol Endocrinol. me20141180 (Aug 2014, PMID 25099013).

3. Patterson C, Portbury AL, Schisler JC, Willis MS. Tear me down: role of calpain in the development of cardiac ventricular hypertrophy. Circ Res 109, 453 (Aug 2011, PMID: 21817165).

4. Pendse A, Lockyer P, Schisler J, Willis M. Konrad Bloch, PhD: Understanding of Cholesterol Metabolism. Labmedicine 42, 370 (May 2011, doi: 10.1309/LM3YCF1I6CCBBZJOR).

5. Zungu M, *Schisler JC, Essop MF, McCudden C, Patterson C, Willis MS. Regulation of AMPK by the ubiquitin proteasome system. Am J Pathol 178, 4 (Jan 2011, PMID: 21224036).

6. Lockyer P, *Schisler JC, Patterson C, Willis MS. Minireview: Won’t get fooled again: the nonmetabolic roles of peroxisome proliferator-activated receptors (PPARs) in the heart. Mol Endocrinol 24, 1111 (Jun 2010, PMID: 20016041).

7. Wilson BA, Schisler JC, Willis MS. Sir Hans Adolf Krebs: Architect of Metabolic Cycles. Labmedicine 41, 377 (May 2010, doi: 10.1309/LMZ5ZLAC85GFMGHU).

8. Moreno-Miralles I, Schisler JC, Patterson C. New insights into bone morphogenetic protein signaling: focus on angiogenesis. Curr Opin Hematol 16, 195 (May 2009, PMID: 19346940).

SCHISLER, JONATHAN C


9. Rodríguez JE, Schisler JC, Patterson C, Willis MS. Seek and destroy: the ubiquitin----proteasome system in cardiac disease. Curr Hypertens Rep 11, 396 (Dec 2009, PMID: 19895750).

10. Willis MS, Schisler JC, Portbury AL, Patterson C. Build it up-Tear it down: protein quality control in the cardiac sarcomere. Cardiovas Res 81, 439 (Feb 2009, PMID: 18974044).

11. Schisler JC, Patterson C. Target Assessment: STIP1 homology and U box-containing protein 1 - [Isoform 1]. Targeted Proteins database (Mar 2008, doi: 10.2970/tpdb.2008.130).

12. Aitsebaomo J, Portbury AL, Schisler JC, Patterson C. Brothers and sisters: molecular insights into arterial-venous heterogeneity. Circ Res 103, 929 (Oct 2008, PMID: 18948631).

13. Schisler JC, Willis MS, Patterson C. You spin me round: MaFBx/Atrogin-1 feeds forward on FOXO transcription factors (like a record). Cell cycle 7, 440 (Feb 2008, PMID: 18235241).

14. Willis MS, Schisler JC, Patterson C. Appetite for destruction: E3 ubiquitin-ligase protection in cardiac disease. Future Cardiol 4, 65 (Jan 2008, PMID: 19543439).

* Indicates co-first authorship



In Press/Submitted Manuscripts 1. McDonough H, Ronnebaum SM, Zhang C, Jie A, Portbury A, Newgard CB, Patterson C, Schisler

JC. Microtubule polymerization, glucose transporter localization, and whole-animal glucose homeostasis disrupted by the loss of CHIP expression. AJP. Submitted (Aug 2014).

Selected Posters, Abstracts, and Oral Presentations 1. Schisler JC, Grevengoed TJ, Ellis JM, Paul DS, Willis MS, Coleman RA. mTOR inhibition reverses

cardiac metabolic derangement caused by the inactivation of fatty acid oxidation. Twelfth Annual Scientific Sessions of the Society for Heart and Vascular Metabolism meeting, Tromso, Norway, Canada (Jun 2014).

2. Campen M, Madden M, Schisler JC, Willis MS. Transcriptional Endothelial Biosensor Response to Diesel-Induced Plasma Compositional Changes. Poster presentation, American Thoracic Society 2014 International Meeting, San Diego, CA (May 2014).

3. Schisler JC, Schuck RN, Hilliard E, Lee, CR, Stouffer GA, Patterson C. Understanding the correlation between coronary artery disease and inflammatory biomarker gene expression signatures from circulating blood cells - identifying pathways that are important to clinical phenotypes in the elderly. Oral presentation, NAVBO Genetics and Genomics of Vascular Disease Workshop, Asilomar, CA (Oct 2012).

4. Lockyer P, Pi X, Schisler JC, Timothy D, Chen Z, Tzima E, Willis MS, Homeister JW, Patterson C. Bmper inhibits expression of inflammatory adhesion molecules and protects against atherosclerosis. Poster presentation, NAVBO Workshops in Vascular Biology, Asilomar, CA (Oct 2012).

5. Rubel CE, Schisler JC, Hamlett ED, DeKroon RM, Alzate O, Patterson C. Diggin’ on U(biquitin). A Novel Method for the Identification of Physiological E3 Ubiquitin-Ligase Substrates. Poster presentation, 4th Ubiquitin and Drug Discovery conference, Philadelphia, PA (Jul 2012).

6. Stephens SB, Schisler J, Hohmeier HE, An J, Sun A, Pitt GS, Newgard CB. A VGF-Derived Peptide Attenuates Development of Type 2 Diabetes Via Specific Effects on Islet β-Cell Mass and Function. American Diabetes Association 71st Scientific Sessions San Diego, CA (2011); published in Diabetes 60, 125-LB (Jun 2011).

7. Schisler JC, Willis MS, Kang E, Patterson C. CHIP directly regulates AMPK activity and its critical regulator of the cardiac stress response to metabolic challenge. Poster presentation, Eighth Annual Scientific Sessions of the Society for Heart and Vascular Metabolism meeting, Kananaskis, Alberta, Canada (Aug 2010).

8. Schisler JC, Willis MS, Patterson C. CHIP mono-ubiquitination activity – effects on cardiovascular metabolism and AMPK activity. Oral presentation, Experimental Biology, Anaheim, CA (Apr 2010); published in FASEB J 24:115.1 (Apr 2010).

9. Willis MS, Li L, Schisler JC, Lockyer P, Patterson C: Muscle ring finger-1 (MuRF1) inhibits spontaneous cardiac hypertrophy induced by the PPARalpha agonist fenofibrate in vivo. Oral presentation, Experimental Biology, Anaheim, CA (Apr 2010); published in FASEB J 24:110.11 (Apr 2010).

10. Schisler JC, Zhang C, Patterson C. A Cardioprotective Role for the E3 Ubiquitin Ligase CHIP During Cardiac Hypertrophy Through a Novel Mechanism of AMPK Regulation. Poster presentation, American Heart Association Scientific Sessions, Orlando, FL (Nov 2009); published in Circulation 120:S761 (Dec 2009).

11. Rodríguez JE, Li L, Schisler JC, Patterson C, Willis MS. The cardiac ubiquitin ligase muscle ring finger-1 (MuRF1) ubiquitinates and degrades PPAR-alpha to regulate fatty acid and glucose metabolism. Poster presentation, American Heart Association Scientific Sessions, Orlando, FL (Nov 2009); published in Circulation 120, S854 (Dec 2009).

12. Rodríguez JE, Schisler JC, Willis MS. The cardiac ubiquitin ligase muscle ring finger-1 (MuRF1) regulates fatty acid and glucose metabolism through its interaction with PPAR-α. Oral presentation,



Seventh Annual Scientific Sessions of the Society for Heart and Vascular Metabolism meeting, Padova, Italy (Aug 2009).

13. Willis MS, Schisler JC, Li L, Rodríguez JE, Patterson C. The cardiac ubiquitin ligase muscle ring finger-1 (MuRF1) inhibits creatine kinase activity in vivo. Poster presentation, Seventh Annual Scientific Sessions of the Society for Heart and Vascular Metabolism meeting, Padova, Italy (Aug 2009).

14. Schisler JC, Zhang C, Patterson C. An unsuspected role for the E3 ubiquitin ligase CHIP in the metabolic response to cardiac hypertrophy via a novel mechanism of AMPK regulation. Oral presentation, Seventh Annual Scientific Sessions of the Society for Heart and Vascular Metabolism, Padova, Italy (Aug 2009).

15. Willis MS, Schisler JC, Lockyer P, Rodríguez JE, Patterson C. The role of muscle ring finger-1 (MuRF1) in fenofibrate-induced cardiac hypertrophy in vivo. Poster presentation, Seventh Annual Scientific Sessions of the Society for Heart and Vascular Metabolism, Padova, Italy (Aug 2009).

16. Schisler JC, Willis, MS, Lockyer P, Patterson C. Activation of PPARα in mice lacking CHIP expression develop spontaneous cardiac hypertrophy. Oral presentation, Seventh Annual Scientific Sessions of the Society for Heart and Vascular Metabolism, Padova, Italy (Aug 2009).

17. Schisler JC, Zhang C, McDonough H, and Patterson C. An Unsuspected Role for Protein Quality Mechanisms in Regulation of Cardiac Fatty Acid Metabolism. Poster presentation, Marie Curie Symposium: The ubiquitin-proteasome system in cardiovascular disease (Jun 2007).

18. Willis MS, Schisler JC, Lockyer P, McDonough, Patterson C: Cardiac muscle ring finger-1 (MuRF1) is cardioprotective in ischemia/reperfusion injury in vivo. Poster presentation, Marie Curie Symposium: The ubiquitin-proteasome system in cardiovascular disease (Jun 2007).

19. Willis MS, Schisler JC, McDonough H, Patterson C. Muscle ring finger-1 (MuRF1) expression shifts cardiomyocyte substrate utilization from fatty acids to glucose. Poster presentation, American Heart Association Scientific Sessions, Orlando, FL (Nov 2007); published in Circulation 116, II-120 (Dec 2007).

20. Jensen MV, Schisler JC, and Newgard CB. PDZ-Binding Kinase /T-LAK Cell-Originated Protein Kinase (PDK/TOPK) is an Nkx6.1-Regulated Gene Involved in Islet Proliferation. Poster presentation, American Diabetes Association 67th Scientific Sessions, Chicago, IL (2007); published in Diabetes 56, A425 (Jun 2007).

21. Fueger PT, Schisler JC, Lu D, Hohmeier HE, and Newgard CB. Trefoil Factor 3-Induced Islet Proliferation Requires EGF Receptor Signaling. Poster presentation, American Diabetes Association 67th Scientific Sessions, Chicago, IL (2007); published in Diabetes 56, A424 (Jun 2007).

22. Collier JJ, Schisler JC, Lu D, Fueger PT, Hohmeier HE, and Newgard CB. Stat5b and Nkx6.1 Confer Discrete and Complementary Protective Effects Against Cytokine-mediated Cell Death and Impairment of Glucose-stimulated Insulin Secretion. Poster presentation, American Diabetes Association 67th Scientific Sessions, Chicago, IL (2007); published in Diabetes 56, A445 (Jun 2007).

23. Schisler JC, Fueger PT, Babu DA, Morgan DO, Mirmira RG, and Newgard CB. The transcription factor Nkx6.1 regulates mature beta cell proliferation through transcriptional regulation of multiple cell cycle genes. Oral presentation, Keystone Symposia – Towards Understanding Islet Biology, Taos, NM (2006).

24. Fueger PT, Schisler JC, Collier JJ, Becker TC, Newgard CB, and Hohmeier HE. Trefoil Factor 3 Regulates Cell Proliferation in Rat Pancreatic Islets and Beta Cells. Poster presentation, American Diabetes Association 66th Scientific Sessions, Washington DC; published in Diabetes 55, A360 (Jun 2006).

25. Ronnebaum SM, Jensen MV, Joseph JW, Schisler JC, Lu D, Becker TC, and Newgard CB. Cytosolic NADP-Dependent Malic Enzyme Regulates Glucose-Stimulated Insulin Secretion in INS-1-Derived 832/13 Cells, but Not Isolated Rat Islets: Potential Role of the Mitochondrial Malate Carrier. Poster presentation, American Diabetes Association 66th Scientific Sessions, Washington DC; published in Diabetes 55, A377 (Jun 2006).



26. Schisler JC, Jensen PB, Taylor D, Mirmira R, Becker TC, Knop F, German MS, Weir G, and Newgard CB. Nkx6.1 expression maintains beta cell phenotype and is necessary for robust glucose-stimulated insulin secretion (GSIS) in INS-1-derived cell lines. Oral presentation, Beta Cell Biology Consortium Investigator Retreat, Chicago, IL (Sep 2004).

27. Schisler JC, Jensen PB, Murase K, Becker TC, and Newgard CB. Evidence for an important role of the glucagon receptor in control of glucose-stimulated insulin secretion. Poster presentation, American Diabetes Association 64th Scientific Sessions, Orlando, FL; published in Diabetes 53, A395 (Jun 2004).

28. Schisler J, Murase K, Ellerman K, Eisen A, German M, Newgard C, and Jensen P. Candidate gene and representational difference analyses identify genes that determine beta-cell phenotype and glucose-stimulated insulin secretion. Poster presentation, American Diabetes Association 63rd Scientific Sessions, New Orleans, LA; published in Diabetes 52, A367 (Jun 2003).

29. Schisler JC, Murase K, Ellerman K, Eisen A, German MS, Newgard CB, and Jensen PB. Identification and characterization of genes that define beta-cell phenotype and confer glucose-stimulated insulin secretion. Oral presentation, Keystone Symposia – Towards Understanding Islet Biology, Keystone, CO (Jan 2003).

30. Brown KC, Schisler JC, Newgard CB, and Johnston SA. Identification of peptides for specific targeting of pancreatic islet beta cells. Poster presentation, American Diabetes Association 62nd Scientific Sessions, San Francisco, CA; published in Diabetes 51, A366 (Jun 2002).

31. Jensen PB, Schisler JC, Knop F, German M, and Newgard CB. The transcription factor Nkx6.1 plays a role in defining beta cell phenotype by suppressing glucagon expression. Poster presentation, American Diabetes Association 62nd Scientific Sessions, San Francisco, CA; published in Diabetes 51, A377 (Jun 2002).

32. Cheng B, Fournier RL, Relue PA, and Schisler J. An experimental and theoretical study of the inhibition of E. coli lac operon gene expression by antigene oligonucleotides. Poster presentation, AIChE Spring National Meeting, Atlanta, GA (Mar 2000).

33. Raja M, Molloy V, Lvovsky L, Akowski J, Schisler J, Kogan Y, Fonstein M, Haselkorn R, and Ulanovsky L. Rhodobacter capsulatus genome sequencing project: DENS technology testing ground. Oral presenation, DOE Human Genome Program Contractor-grantee Workshop VI, Santa Fe, NM (Nov 1997).

Invited Presentations 1. Cellular stress responses and the effects on metabolism and cardiac function. Cardiopulmonary &

Immunotoxicity Branch Summer Lunch-and-Learn Session, United States Environmental Protection Agency, Research Triangle Park, NC (Sep 2014)

2. Fish and CHIPs: Identifying a causal mutation for Gordon Holmes Syndrome in the ubiquitin ligase CHIP. Molecular Medicine Alumni Symposium, 30th Anniversary of the UT-Salford Exchange Program, University of Toledo, Toledo, OH (Apr 2014).

3. The bridge between protein quality control and metabolic homeostasis during cardiac pressure overload. Pathology & Lab Medicine Grand Rounds, UNC School of Medicine, Chapel Hill, NC (Apr 2013).

4. Signaling pathways in myocardial hypertrophy redux: An unsuspected role of CHIP in myocardial hypertrophy. Gordon Research Conference – Insulin-like Growth Factors, Ventura, CA (Mar 2009).

5. Ubiquitin ligases in the heart. 4th International Conference – Ubiquitin, Ubiquitin-Like Proteins & Cancer, Houston, TX (Feb 2008).

Patents 1. US Patent #8,580,732: Peptide therapy for hyperglycemia. 2. US Patent Pending: Methods and compositions for treatment of diabetes and related disorders

(#20,070,243,177).



3. US Patent Pending: Prognostic and predictive gene signature for non-small cell lung cancer and adjuvant chemotherapy (#20,120,077,687).

TEACHING ACTIVITIES McAllister Heart Institute Discovery Biology Works-in-progress 2014 – present Director and moderator Research fellows and PhD graduate students (18) in the McAllister Heart Institute University of North Carolina, Chapel Hill, NC Pathology 723: Translational Pathology and Laboratory Medicine 2009 – present Instructor PhD graduate students (17) University of North Carolina, Chapel Hill, NC Course Directors: Monte Willis, MD, PhD/Christopher McCudden, PhD

Topics: Transcriptomics, gene expression analyses, qPCR, microarrays, next-generation sequencing Feb 03, 2009: Cardiovascular Disease I: Transcriptomics Feb 01, 2011: Cardiovascular Disease I: Transcriptomics

Pathology 667: Pathobiology of Cardiovascular Disease 2009 – present Instructor PhD graduate students (12) University of North Carolina, Chapel Hill, NC Course Directors: Monte Willis, MD, PhD/Jonathon Homeister, MD, PhD Topics: Heart metabolism, cardiac development, cardiac hypertrophy, cardiomyopathies.

Feb 10, 2011: Cardiac Metabolism in Heath and Disease II Feb 08, 2011: Cardiac Metabolism in Heath and Disease I Apr 23, 2009: Cardiac Metabolism in Heath and Disease II Apr 21, 2009: Cardiac Metabolism in Heath and Disease I

Carolina Cardiovascular Biology Center (CCBC) Journal Club 2007 – 2009 Director and moderator Research fellows and PhD graduate students (24) University of North Carolina, Chapel Hill, NC BIOE 6310: Biotechnology and Bioprocessing Core Course 1999 – 2000 Graduate teaching assistant, lecturer, and lab supervisor Masters of Science graduate students (24) University of Toledo, OH Course Director: Patricia A. Relue, PhD

BIOE 3300: Bioinstrumentation and Measurement Electronics 1998 – 2000 Graduate teaching assistant, lecturer, and lab supervisor (18) Senior level undergraduate students University of Toledo, OH Course Director: Frank J. Kollarits, PhD (Associate Professor Emeritus) Laboratory/Research Teaching 2007 – present University of North Carolina, Chapel Hill, NC



One on one and small group teaching of small animal techniques, wet laboratory techniques, scientific writing, scientific presentation, and scientific methods to a diversity of undergraduate students, medical students, and post-doctorate trainees from both clinical and PhD backgrounds. Trainees:

– Holly McDonough, Research Associate, McAllister Heart Institute (Jan 2014 – present) – Sarah M. Ronnebaum, Research Associate, McAllister Heart Institute (Jan 2014 – present) – Jennifer Samples, MD, Research fellow, UNC Department of Surgery (Apr 2013 – present) – Lei Xu, Visiting Scholar, Shandong University (Sep 2012 – present) – Carrie Rubel, BS, PhD Student, Pharmacology (Jan 2011 – present) – Bob Schuck, PharmD, PhD Student, Pharmacy (Jul 2011 – Jun 2013) – Brian Gibbs, BS, PhD Student, Biological & Biomedical Sciences Program (Jan 2009 – Apr

2009) – Nhi Nguyen, Undergraduate student, UNC Department of Chemistry (Aug 2007 – May 2008)

Graduate Student Committee Member 2012 – present University of North Carolina, Chapel Hill, NC Current Committees Harlyn Skinner, Gillings School of Global Public Health, PhD Candidate Carrie Rubel, Department of Pharmacology, PhD Candidate

GRANTS Current Ono Pharma, USA, Inc. Jan 2013 – Jan 2016 Structural and functional analysis of CHIP/chaperone complexes (A13-0745) Principal Investigator (40% Effort), $670K/3 years

Foundation Leducq Jan 2012 – Dec 2016 Proteotoxicity: an unappreciated mechanism of heart disease and its potential for novel therapeutics Team Member (10% Effort), $5.4M/5 years National Heart, Lung, and Blood Institute, NIH Apr 2010 – May 2015 Center to Reduce CVD Disparities: Genes, Clinics, and Communities (P50HL105184) Principal Investigator (30% Effort), $7.0M/5 years National Institute of General Medical Sciences, NIH Jan 2014 – Aug 2015 CHIP: A Link Between the Chaperone and Proteasome Systems (R01GM061728) Principal Investigator (20% Effort), $840K/4 years, initial award Completed American Heart Association Jul 2008 – Jun 2010 The role of the cellular stress response in the regulation of metabolism and autophagy during cardiac hypertrophy Principal Investigator, $85K/2 years University of North Carolina Investments for the Future Jun 2007 – Jun 2010 Understanding clinical cardiovascular disease and health disparities using a systems biology approach Research fellow, $750K/3 years

National Heart, Lung, and Blood Institute, NIH Jul 2006 – Jul 2007



University of North Carolina at Chapel Hill Clinician-Scientist Training Program in Cardiovascular Medicine Research fellow, $40K, 1 year

PROFESSIONAL SERVICE To discipline 1. Chair of Biomarkers and Genetics Workgroup for NIH Centers for Population Health and Health

Disparities (2010 – present). 2. Symposium Chair, American Society of Investigative Pathology, Experimental Biology 2010:

“Pathobiology of Cardiac Disease Mini-Symposium” (Apr 2010). 3. Associate Faculty Member, Faculty of 1000 (2008 – present). 4. Ad hoc Manuscript Peer-Reviewer

a. Journal of Clinical Investigation b. Journal of Biological Chemistry c. Toxicological Sciences d. Cardiovascular Research e. Journal of Molecular and Cellular Cardiology f. Gene g. The American Journal of the Medical Sciences h. Cardiovascular Pathology i. Molecular Medicine

Within UNC-Chapel Hill 1. Organizer of Poster and Oral Presentation judging, Integrated Vascular Biology/McAllister Heart

Institute Annual Symposium (Mar 2012). 2. Poster judging of graduate students, Department of Pathology’s Annual Research Symposium (Sep

2010). 3. Poster judging of graduate students, Department of Pathology’s Annual Research Symposium (Sep

2009). PROFESSIONAL MEMBERSHIPS Member, North American Vascular Biology Organization 2012 – present Member, American Heart Association 2012 – present Member, American Society for Investigative Pathology 2012 – present Member, The Science Advisory Board 2009 – present Member, American Society for Investigative Pathology 2009 – 2010 Member, American Heart Association 2007 – 2010



RESEARCH STATEMENT Research Philosophy and Goals Since the beginning of my research endeavors in an undergraduate research laboratory, I envisioned a career of being an enthusiastic and supportive mentor, a fair and inspiring team leader, and an “outside of the box” research scientist whose goal it would be to utilize basic science skills combined with clinical approaches to help understand physiology and disease. Now that I find myself as a burgeoning independent researcher, my primary goals are to:

(1) Teach basic science and laboratory skills to trainees using hypothesis-driven research methodologies;

(2) Develop strong scientific communication skills in trainees including oral and written approaches; (3) Serve as a mentor and role model just as those have mentored me in the past, to inspire both

personal and scientific development in students and trainees. Research Interests The common theme of my research interests is the use of clinical-based discoveries to explore the biology of health and disease, focusing on the underlying molecular pathways and mediators that can be exploited for the prevention and treatment of human diseases. My research is coordinated through utilizing clinical data as a source of biological discovery that is in turn interrogated through hypothesis driven research methodologies. Thanks to the influence of my postdoctoral advisor Dr. Cam Patterson, much of my research is focused within the arena of protein quality control mechanisms in the cardiovascular system. The ability of cells to maintain protein integrity and regulate protein turnover (otherwise known as protein quality control) is critical for normal cell function. However, the process of protein quality control is often exploited and hijacked during disease pathogenesis. My group studies the mechanisms by which protein quality control affects physiological function of various organ systems, including the heart, brain, skeletal muscle, and neuroendocrine system. We then utilize disease models to determine how protein quality control systems either adapt or maladapt in the face of cellular stress. Although protein quality control mechanisms are classically viewed as cytosolic events, we are also actively investigating the genetic component of this process by determining how quality control mechanisms function in the nucleus and how these mechanisms impact cellular aging and DNA repair pathways. My group is also involved in ongoing clinical studies that focus on cardiovascular function and heart health, including hypertension and lifestyle interventions that focus on genetic variation and global changes in gene expression with the goal to integrate novel observations into models that can be tested in cell culture and animal models. In our lab, state-of-the-art approaches in molecular and cellular biology, biochemical techniques, protein chemistry, mouse genetics, and bioinformatics are used to generate and interrogate these biological questions. My vision for the future is expanding my translational work with CHIP (C-terminus of HSC70-Interacting Protein) and other important mediators of protein quality control by developing a large multi-disciplinary laboratory with a strong postdoctoral fellow base in order to train the next generation of medical students, graduate students, residents, and fellows in translational medicine. Current Projects NIH R01GM061728, CHIP: A LINK BETWEEN THE CHAPERONE AND PROTEASOME SYSTEMS The major goal of this project is to characterize the function of a ubiquitin ligase, CHIP, discovered in the Patterson laboratory. This project explores the molecular mechanisms that are dependent on CHIP function in the context of protein quality control in cardiac health as well as diseases such as cardiac hypertrophy. § Protein Quality Control- CHIP was originally identified in a screen for proteins upregulated during

the cellular stress response. Research by the Patterson laboratory and others discovered that CHIP is a dual function protein: not only does it bind to cellular chaperone proteins, to enhance the folding of target proteins into their native conformation, but CHIP also has ubiquitin ligases activities. CHIP’s



activity in both arms of the protein quality control network (i.e. protein degradation and protein re-folding) makes it a fascinating protein to study. To date, I have published the following key observations: o CHIP expression in the heart is critical to withstanding the increased cardiac demands brought

about by hemodynamic stress; o Identification of the first physiological substrate of CHIP’s autonomous chaperone activity – the

metabolic enzyme AMP-activated kinase (AMPK); o AMPK activity can be further enhanced independent of changes in phosphorylation, likely

through CHIP-induced conformational changes to the catalytic domain of AMPK; o The process of stress-dependent protein quality control and regulation of energy metabolism in

the heart are not only coordinated but are essential to cardiac function. Given the pivotal role of CHIP and its regulation of cardiac metabolism in health and disease, this work forms the basis for a new R01 award that is completed and will be submitted in February and includes: o Characterizing the role of CHIP on cellular metabolism through the ubiquitin- and chaperone-

dependent regulation of the AMPK signaling axis; o Discovering CHIP’s contribution to the activity and stability of nuclear protein substrates and

direct association with chromatin. § Human Genetics of Ataxia, Hypogonadism, & Cardiomyopathies- In collaboration with Dr. Yu-Ming

Xu from The First Affiliated Hospital of Zhengzhou University in China, I identified the first clinically relevant mutation in CHIP in a family with two afflicted sisters with Gordon Holmes Syndrome. Biochemical characterization of this mutation combined with data gleaned from our CHIP knockout mouse model demonstrated how this mutation results in the loss of CHIP’s ubiquitin ligase activity and causes cerebellar ataxia and hypogonadism in humans.

The emerging evidence of common pathways implicated in neurodegenerative diseases and cardiomyopathies and the identification of clinically relevant mutations in CHIP, as well as other genes involved in protein ubiquitination, provides a foundation to further build upon my previous studies of CHIP as it pertains to maintaining protein homeostasis in both in the heart and brain. The continuation of this line of studies is included in my upcoming R01 submission as well as being used as the preliminary data in collaboration with Dr. Xu for a National Natural Science Foundation of China grant to fund major international joint research projects that includes: o Determining how defective CHIP function associated with Gordon Holmes Syndrome impacts

the structure and function of CHIP; o Knock-in mutation analysis of causal cerebellar ataxia human polymorphisms in cell culture and

animal models; o Molecular characterization and comparisons of neuropathologies and cardiomyopathies

associated with mutations in ubiquitin ligases. NIH, P50HL105184, REDUCING CVD DISPARITIES: GENES, CLINICS, AND COMMUNITIES This clinical study focuses on minority populations in a rural population at high risk for cardiovascular disease (CVD). We are now in the final year of two different clinical interventions: (1) hypertensive patients being treated with a pharmaceutical approach to control blood pressure; and (2) patients enrolled in a lifestyle change program aimed at decreasing risk factors associated with CVD. I completed the genome-wide genotyping of both cohorts and am currently focusing on three primary genomic outcomes.

o Determining the prevalence of genomic risk signatures in high-risk community populations using genome-wide association studies;

o Developing and evaluating novel genomic models incorporating high-risk features (including socio-economic factors) in this population to design patient- and genomic-specific interventions;



o Modeling genomic signatures that can be used to predict responsiveness to interventions that underlie CVD disparities. Early detection through genetic variation profiling prior to the onset of symptoms will allow early lifestyle intervention and reduce the number of deaths associated with CVD.

Preliminary work from this study led to the development of an R21 grant proposal submitted in December titled Epigenetic dynamics of hypertension in African American females. SAMARA: SUPPORTING A MULTIDISCIPLINARY APPROACH TO RESEARCH IN ATHEROSCLEROSIS The SAMARA project applies recent, major advances in biomedical and computational sciences to develop a deeper understanding of human CVD. This project centers on the identification of expression patterns, genotypes, biomarkers, and metabolites associated with various cardiovascular risk factors such as smoking and carbohydrate metabolism. These studies were instrumental in allowing me to learn how to integrate large transcriptional datasets with basic research approaches and have yielded new insights into cardiovascular biology and coronary artery disease (CAD) including:

o The effect of tobacco usage on large sets of genes involved in proliferation and apoptosis likely increasing the incidence of neoplasia;

o The coordinated transcriptional adaptation of carbohydrate metabolism to dietary environmental pressures, suggesting a genetic and transcriptional mechanism for the disproportionate levels of obesity, diabetes, and cardiovascular disease observed in North Carolinians of African ancestry.

I have now completed the analysis of the second enrollment phase of SAMARA that focused specifically on the elderly and which also included quantitative analysis of circulating inflammatory mediators. This study is being prepared for submission for publication and revealed:

o In the elderly, gene expression patterns associated with the presence and severity of obstructive CAD reflected differential-expression of genes regulating multiple processes, most notably, key genes regulating the inflammatory response;

o Plasma levels of established systemic or vascular inflammatory biomarkers were not elevated in older patients with obstructive CAD;

o The identification of novel expression quantitative trait loci that correlate with obstructive CAD in an elderly population, suggesting a genomic influence in the severity of CAD and opening the door to new pathways not previously attributed to coronary disease.

In collaboration with several UNC faculty members, future studies utilizing this dataset have been initiated with a wide range of disciplines represented including:

o Dr. Craig Lee (School of Pharmacy) – investigating the contribution of cytochrome P450 eicosanoid metabolism to clinically relevant features of coronary artery disease in humans;

o Dr. Joan Taylor (Department of Pathology & Laboratory Medicine) - Role of the Rho-GAP GRAF3 in the pathogenesis of human hypertension;

o Dr. Liza Makowski (Department of Nutrition) - confirming a role for GLUT1 or FATP1 in human diabetes risk.

Industry Funded Projects ONO PHARMACEUTICALS, STRUCTURE AND FUNCTION OF CHAPERONES Since becoming a Research Instructor in the Department of Medicine at UNC I have been successful in securing my own funding in the form of a sponsored research award providing $670,000 of research support over two years. I have formed a collaborative group of leading structural NMR and crystallography scientists including:



o Dr. Walter Chazin (Vanderbilt) o Dr. Rick Page (Miami, OH) o Dr. Saurav Misra (Cleveland Clinic) o Dr. Michael Miley (UNC – Pharmacology)

This grant focuses on three primary objectives:

o Solution NMR-based approach to identify the structural interface between CHIP and chaperone proteins;

o Transcriptional responses in CHIP-depleted primary neurons in response to protein aggregation; o Proteomic analysis of chaperone complexes in the presence or absence of CHIP during protein

aggregation in cortical neurons. Mentored Project During the past two years, I have trained an outstanding Pharmacology PhD candidate, Ms. Carrie Rubel, who is keenly interested in translational research. The aim of Ms. Rubel’s research is to understand how recently identified mutations in the coding region of CHIP directly manifest the neuronal, endocrine, and cardiovascular pathologies found in humans with CHIP polymorphisms. I have worked to mentor Ms. Rubel in her daily research and together, she and I recently published a manuscript detailing new methodologies to identify substrates of ubiquitin ligases, such as CHIP, and an additional publication describing the role that CHIP mutations play in the development of Gordon Holmes Syndrome. Through my encouragement, she presented at a national ubiquitin conference and recently spent two weeks in a collaborators laboratory in Germany to learn how to process animal tissue for measuring protein turnover of the entire proteome using stable isotope labeling with amino acids. She also was awarded a predoctoral fellowship through the American Heart Association, clearly reflective of her potential as an independent researcher.

TEACHING STATEMENT

Throughout my graduate training and into my faculty appointment at UNC, I have been fortunate to be given opportunities to be involved in traditional classroom teaching. Although classroom teaching was not an emphasis of my previous mentors, my decision to enter scientific research as a career was due to a single undergraduate biology instructor – so I wholeheartedly understand the impact and importance of teaching. Simply stated, my primary goal as a course instructor is to inspire students just as those have inspired me in the past, to encourage both personal and scientific development in the classroom. Much like my research approach, there is a strong molecular biology core to all my lectures, and I work hard to bring the more practical aspects of basic science to graduate students to demonstrate the clinical applications of the underlying mechanistic basic science with which they are familiar.

Didactic teaching in the UNC graduate college Over the last 4 years, I have had the opportunity to teach in two new courses in the UNC graduate school: Translational Medicine (Pathology 723) and Advanced Pathobiology of Cardiovascular Disease (Pathology 667). By the end of the Spring, 2011 semester, I lectured in the Translational Medicine twice and the Advanced Pathobiology of Cardiovascular Disease four times. Previously, Pathology 723 served as a primer on the clinical field of Pathology. When a new director of the course was assigned, Dr. Monte Willis, he expressed his desire to re-focus the course to more broadly teach the processes involved in translating scientific discoveries into clinical laboratory tests. It was a great opportunity for me to be involved in that process of revamping a course as my lectures were built off of my own research successes in studying gene transcription and how system-based approaches can be used as both a discovery platform for new biology as well as be used to develop clinical tests.



The Advanced Pathobiology of Cardiovascular Disease course focuses on the molecular and cellular biology underlying a host of clinical diseases and is taught by both clinicians from a variety of disciplines and translational basic scientists. Two thirds of each class session is devoted to interactive didactic presentations; the remaining time is used for a discussion of relevant primary literature that I assign. The overall goal of my lectures in Advanced Pathobiology of Cardiovascular Disease is to help graduate students develop an understanding of the basic science underlying clinically relevant diseases.

Evaluations In both courses I have placed in the top half of all 15 instructors as ranked by the students. For Path 667 and 723 the course directors provided evaluation feedback and are summarized here (scale 1 to 5, 5 representing the highest score): Path 667 – Advanced Pathobiology of Cardiovascular Disease Schisler Aggregate (n = 15) 1. The session’s content was appropriate to meet the learning objectives. 4.8 4.4 ± 0.2 2. The content was presented in a logical, organized sequence. 4.4 4.4 ± 0.3 3. The instructor’s delivery of the presentation was engaging. 4.4 4.3 ± 0.5 4. The instructor emphasized key points clearly. 4.6 4.4 ± 0.3 5. The instructor’s audio/visual aids were supportive of, and coordinated

with, the verbal presentation. 4.6 4.4 ± 0.2

6. Overall these lectures enhanced my understanding of basic pathology. 4.6 4.3 ± 0.3

Path 723 – Translational Medicine Schisler Aggregate (n = 15) Overall score (from 20 criteria) 4.4 4.2 ± 0.4