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1 Harvard Medical School/Harvard School of Dental Medicine Format for the Curriculum Vitae Date Prepared: February 13, 2019 Name: Timothy T. Hla, Ph.D. Office Address: Vascular Biology Program, Boston Children’s Hospital, Department of Surgery, Harvard Medical School, Karp Building 12.211, 1 Blackfan Street, Boston, MA 02115 Home Address: 28 Chatham Circle, Wellesley, MA 02481, USA Work Phone: 617-919-2179 Work Email: [email protected] Work FAX: Place of Birth: Rangoon, Burma Education 1978-1981 M.B.,B.S. (withdrawn) Rangoon University 1981-1982 B.S. (Biology) Western Illinois University 1983-1988 Ph.D. (Biochemistry) (J. Martyn Bailey) The George Washington University Postdoctoral Training Jan 1988- Dec 1990 Postdoctoral Fellow Holland Laboratory (Thomas Maciag) American Red Cross Faculty Academic Appointments Jan 1991- March 1994 Scientist I Molecular Biology, Holland Laboratory American Red Cross March1994- August1996 Scientist II Molecular Biology, Holland Laboratory American Red Cross Jan 1992- August1996 Adjunct Assistant Professor Genetics Graduate Program The George Washington University August1996 -Dec 2000 Associate Professor Physiology University of Connecticut School of Medicine Dec 2000- Aug 2009 Professor Cell Biology, Genetics and Developmental Biology University of Connecticut School of Medicine Aug 2009- 2017 Adjunct Professor Cell Biology, Genetics and Developmental Biology University of Connecticut School of Medicine Aug 2009- Sept. 2016 Professor Pathology and Laboratory Medicine & Neuroscience Weill Medical College of Cornell University

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Page 1: Format for the Curriculum Vitae - University of Virginiatraining.cvrc.virginia.edu/events/796resume.pdf · Sept. 2016 - present Adjunct Professor Pathology and Laboratory Medicine

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Harvard Medical School/Harvard School of Dental Medicine Format for the Curriculum Vitae

Date Prepared: February 13, 2019

Name: Timothy T. Hla, Ph.D.

Office Address: Vascular Biology Program, Boston Children’s Hospital, Department of Surgery, Harvard Medical School, Karp Building 12.211, 1 Blackfan Street, Boston, MA 02115

Home Address: 28 Chatham Circle, Wellesley, MA 02481, USA

Work Phone: 617-919-2179

Work Email: [email protected]

Work FAX:

Place of Birth: Rangoon, Burma

Education

1978-1981 M.B.,B.S. (withdrawn) Rangoon University 1981-1982 B.S. (Biology) Western Illinois University 1983-1988 Ph.D. (Biochemistry)

(J. Martyn Bailey) The George Washington

University

Postdoctoral Training

Jan 1988-Dec 1990

Postdoctoral Fellow Holland Laboratory (Thomas Maciag)

American Red Cross

Faculty Academic Appointments

Jan 1991-March 1994

Scientist I Molecular Biology, Holland Laboratory

American Red Cross

March1994-August1996

Scientist II Molecular Biology, Holland Laboratory

American Red Cross

Jan 1992-August1996

Adjunct Assistant Professor

Genetics Graduate Program The George Washington University

August1996-Dec 2000

Associate Professor Physiology University of Connecticut School of Medicine

Dec 2000-Aug 2009

Professor Cell Biology, Genetics and Developmental Biology

University of Connecticut School of Medicine

Aug 2009-2017

Adjunct Professor Cell Biology, Genetics and Developmental Biology

University of Connecticut School of Medicine

Aug 2009- Sept. 2016

Professor Pathology and Laboratory Medicine & Neuroscience

Weill Medical College of Cornell University

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Sept. 2016 - present

Adjunct Professor Pathology and Laboratory Medicine

Weill Medical College of Cornell University

Sept 2016- Present

Patricia K. Donahoe Professor

Surgery Harvard Medical School

Sept 2016- Present 2016- present 2016- present 2017- present

Investigator Member Member Associate Member

Vascular Biology Program Immunology Graduate Program Cancer Biology Program Chemical Therapeutics and Genomics programs

Boston Children’s Hospital Harvard Medical School Dana Farber Cancer Institute, Harvard Cancer Center The Broad Institute of Harvard and MIT

Other Professional Positions

2007-2010 Scientific and Medical Advisory Board HHT Foundation International

Major Administrative Leadership Positions Local 1997-2000 Director, Cell Biology Graduate Program University of Connecticut School of

Medicine 1998-2009 Director, Center for Vascular Biology University of Connecticut School of

Medicine 2009-2016 Director, Center for Vascular Biology,

Department of Pathology and Laboratory Medicine

Weill Medical College of Cornell University

2013-2016 Program Co-Chair, Tumor Microenvironment Research Program

Meyer Cancer Center, Weill Medical College of Cornell University

Regional 2013-2014 President New York Lipid and Vascular Biology

Research Club National and International 2003, 2007, 2009

Meeting Co-Organizer, Summer Research Conference on Lysophospholipids

FASEB

2009, 2011 Meeting Organizer, Workshop on Vascular Cell Signaling

North American Vascular Biology Organization (NAVBO)

2011 Meeting Co-Organizer Gordon Research Conference: Vascular Cell

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Biology 2013 Meeting Organizer Gordon Research Conference: Vascular Cell

Biology

Committee Service Local 1996-1997 Alliance Committee on Research,

Department of Cardiology 1996-1997

University of Connecticut Health Center, Hartford Hospital Committee Member

1996-1999 HCRAC Grants Committee 1996-1999

University of Connecticut Health Center Committee Member

1996-2000 Search Committee on Vascular Biology 1996-2000

University of Connecticut Health Center Committee Member

1997-2000 Graduate Programs Committee 1997-2000

University of Connecticut Health Center Committee Member

1998 Search Committee for Division Chief of Cardiology 1998

University of Connecticut Health Center Committee Member

1998 Space Committee For Research 1998

University of Connecticut Health Center Committee Member

1998 Subcommittee on Training Grants 1998

University of Connecticut Health Center Subcommittee Member

1999 Scientific Advisory Committee, Program Project on Osteoporosis 1999

University of Connecticut Health Center Committee Member

2000-2003 School of Medicine Compensation Committee 2000-2003

University of Connecticut Health Center Committee Member

2001-2004 Health Center Research Advisory Committee 2001-2004

University of Connecticut Health Center Committee Member

2002-2004 UConn Science Commercialization Advisory Committee 2002-2004

University of Connecticut Committee Member

2003 UConn School of Medicine Bylaws Committee 2003

University of Connecticut Committee Member

2006-2009 Institutional Research Recruitment Committee 2006-2009

University of Connecticut Committee Member

2006-2009 UConn Science Commercialization Advisory Committee 2006-2009

University of Connecticut Committee Member

2007 UConn Presidential Search Committee 2007

University of Connecticut Committee Member

2007-2008 UConn Health Center EVP/Dean Search Committee

University of Connecticut

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2007-2008 Committee Member 2010-2015 Faculty Search Committee, Department of

Medicine, Division of Cardiology 2010-

Weill Cornell Medical College Committee Member

2010-2012 Faculty Search Committee, Department of Cell and Developmental Biology 2010-2012

Weill Cornell Medical College Committee Member

2011-2013 Basic Science At-Large Committee 2011-2013

Weill Cornell Medical College Representative

2012-2013 Dean’s Advisory Committee for Research Computing 2012-2013

Weill Cornell Medical College Committee Member

2012-2013 Research Planning Committee 2012-2013

Weill Cornell Medical College Committee Member

2012-2015 Committee for Review 2012-2015

Weill Cornell Medical College Committee Member

2012-2015 Core Services Committee 2012-2015

Weill Cornell Medical College Committee Member

2013-2016 Bridge Funding Committee 2013-

Weill Cornell Medical College Committee Member

2013-2016 Budget Restructuring Committee 2013-

Weill Cornell Medical College Committee Member

2014 Faculty Search Committee, Department of Pharmacology 2014-2015

Weill Cornell Medical College Committee Member

2015-2016 Research Awards Committee

Weill Cornell Medical College Committee Member

2015- 2016 Metabolic Institute Chair Search Committee Weill Cornell Medical College Committee Member 2014-2016 Cardiovascular Institute Chair Weill Cornell Medical College Search Committee 2018 Dept. Cardiology Faculty Search committee Boston Children’s Hospital Committee Member Regional 2013- Scientific Advisory Committee, Maine Committee Member Medical Center Research Institute, Portland, ME

National and International

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2009-2011 2014-

Arteriosclerosis, Thrombosis and Vascular Biology Scientific Program Committee External Advisory Member, NHLBI PPG UCLA (Alan Fogelman)

American Heart Association Committee Member

Committee Member

Professional Societies 1988- American Society for Cell Biology (ASCB)

Member

1991- American Association for the Advancement of Science (AAAS)

Member

1996- North American Vascular Biology Organization (NAVBO) 1996-2005 2005-2008 2008-2010 2010-2011 2011-2012 2012-

Member Councilor Secretary Treasurer President-Elect President Member

2001-

American Society for Biochemistry and Molecular Biology (ASBMB)

Member

Grant Review Activities 1992-1994 Veterans Administration Merit Grant

Review Committee 1992-1994

Veterans Administration Member

1995 General Clinical Research Center Site Visit Team 1995

NCRC, NIH Member

1995 NICHD P01 Reverse Site-Visit Team 1995

NICHD Member

1996 NHLBI SCOR Pulmonary Fibrosis Study Section 1996

NHLBI SCOR Member

1996-1998 National Vascular Wall Biology Study Section 1996-1998

American Heart Association Member

1997-1998 Research Committee 1997-1998

Connecticut Affiliate of the AHA Member

1998 Northeast Review Panel 1998

American Heart Association Member

1998-2002 Pathology A Study Section NIH

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1998-2002 Member 1999 Program Project Review Committee

1999 NIDCR, NIH Ad-Hoc Member

2000-2008 Program Project Review Committee 2000

NHLBI Ad-Hoc Member

2002 Program Project Review Committee 2002

NHLBI Ad-Hoc Member

2004-2008 Program Project Parent Committee 2004-2008

NHLBI Member

2008 Program Project Review Committee 2008

NHLBI Ad-Hoc Member

2010 NHLBI Advisory Committee on Clinical and Translational Research in Vascular Biology 2010

NHLBI Member

2011 2011

NHLBI Intramural Program Review 2011 VCMB study section, CSR, NIH

NHLBI, NIH Ad-Hoc Member Ad-Hoc Member

2013 NHLBI Intramural Program Review

NHLBI, NIH Ad-Hoc Member

2016 2016 2017 2017

Fondation Leducq Midterm Review Fondation Louis-Jeantet award review NHLBI R35 Review NIH VCMB Study Section, CSR, NIH

Ad-Hoc Member Ad-Hoc Reviewer NHLBI, NIH Ad-Hoc Member Ad-Hoc Member

2018 NIH Director’s Pioneer Award study section Ad-Hoc Member 2018 Israel Science Foundation Grant review Ad-Hoc reviewer 2018 Deutsche Forschung Gemeinschaft (DFG) Program Project Review Mannheim, Germany

Editorial Activities Ad-Hoc Reviewer for the following journals American Journal of Physiology American Journal of Respiratory Cell and Molecular Biology Atherosclerosis, Thrombosis and Vascular Biology Biochemical Pharmacology Blood Cancer Research Cell Cell Metabolism Circulation Circulation Research

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Development Developmental Cell FEBS Journal Gastroenterology Genes and Development Journal of Biological Chemistry Journal of Clinical Investigation Journal of Experimental Medicine Journal of Immunology Journal of Leukocyte Biology Journal of Lipid Research Journal of Thrombosis and Hemostasis Microcirculation Molecular and Cellular Biology Molecular Cell Molecular Pharmacology Nature Nature Cell Biology Nature Medicine Nature Neuroscience Nature Reviews Drug Discovery Nature Reviews Immunology Nature Reviews Molecular and Cellular Biology New England Journal of Medicine Proceedings of the National Academy of Sciences Science Science Translational Medicine Science Signaling The Journal of Physiology

Other Editorial Roles 2002- Editorial Board Member Vascular Pharmacology 2002-2005 Editorial Board Member The FASEB Journal 2002-2007; 2017-2022

Editorial Board Member The Journal of Biological Chemistry

2003-2010 Editor-in-Chief Prostaglandins and Other Lipid Mediators 2007- Editorial Board Member Atherosclerosis, Thrombosis and Vascular

Biology 2018- Editorial board Member Vascular Biology

Honors and Prizes

1986 Sigma Xi Scientific Honor Society

George Washington University

1988 Roland Lange Fellowship

American Red Cross

1988 Postdoctoral Fellowship

Arthritis Foundation

1999 Established American Heart Association

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Investigator 1999 Biomol Young

Investigator Award International Eicosanoid Meeting

2003 Dennis Woznicki Lecturer

Baylor College of Medicine, Department of Pathology

2007 Honorary Member Japanese Biochemical Society 2006 MERIT Award NHLBI, NIH 2010 College of CSR

Reviewers CSR, NIH

2014 Highly Cited Researcher

Thompson Reuters

2014 Siegel Award for Outstanding Medical Research

Weill Cornell Medical College, Cornell University

2015 Outstanding Achievement Award

Eicosanoid Research Foundation

2015 Doctor of Medicine (honoris causa)

Goethe University, Faculty of Medicine, Germany

2016 Member, PLUTO Society American Assoc Univ. Pathologists 2016 Fellow American Association for the Advancement of Science 2017-2024 Outstanding Investigator NHLBI, NIH Award (R35) Report of Funded and Unfunded Projects Funding Information Past

1992-2002 Role of EDG-1 in angiogenesis NIDDK

1993-2014 Post-transcriptional mechanisms and vascular inflammation NIH R01-HL49094 PI

1999-2004 Established Investigator Grant American Heart Association

2002-2007 COX-2 and mammary cancer NCI

2002-2014 Interactive signaling modules in vascular inflammation National Institutes of Health P01-HL70694 PI (PI was changed to Dr. Linda Shapiro after my move to WCMC.)

2006-2016 Sphingolipid mediators of vascular growth and homeostasis NIH R37-HL67330 (MERIT)

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PI 2007-2009 Imaging sphingosine 1-phosphate receptors in vivo

Bracco, Inc. PI

2008-2009 S1P1 receptor and tumor angiogenesis AstraZeneca PI

2014-2017 Sphingosine 1-phosphate receptors and vascular pathophysiology NIH R01HL89934 PI

Current

2012-2017 Mechanisms of chemoprevention of cancer NIH P01-CA-77839 (PI: DuBois RN, Mayo Clinic Arizona) Project 3: Sphingolipid mediators and intestinal tumorigenesis PI ($187,500/annum direct costs)

2012-2017 Personalization of therapeutic efficacy and risk NIH U54-HL117798 (PI: Fitzgerald GA, University of Pennsylvania) Mouse Models Core Project Leader ($84,000/annum direct costs)

2014-2019 Sphingosine 1-phosphate signaling in neurovascular biology and disease (SphingoNet) Fondation Leducq Transatlantic Network (PI: Hla T) Co-PI ($1.2M total costs/ annum)

2016-2019 Development of ApoM-S1P axis-based therapeutics to control vascular injury (PI- Timothy Hla) ONO Pharmaceuticals Inc. (PI: Hla T). ($ 300,000 direct costs/ annum). 2017-2024 Sphingosine 1-phosphate signaling in vascular biology and disease (R35 NHLBI outstanding investigator award. (PI: Hla T). ($ 500,000 direct costs/ annum).

Current Unfunded Projects

2016-2021 Sphingosine 1-phosphate signaling in vascular biology and disease (PI: Hla, T) NHLBI, NIH program project grant 2016-2021 Sphingolipid signaling in cardiac development and regeneration (multi PI RO1 grant: Evans, T., Hla, T and Poss, K), NHLBI, NIH Report of Local Teaching and Training Teaching of Students in Courses 1985-1987 Undergraduate students Immaculata College High School,

Rockville, MD Part-time Faculty

1992-1996 Current Topics in Genetics Ph.D. Program

GWUMC

1994 Biochemistry of Nucleic Acids Ph.D. Program

GWUMC

1996-2002 Cell Biology Journal Club UCHC

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Ph.D. Program 1997-2000 Responsible Conduct in Research: Issues in

Authorship Ph.D. Program

UCHC

1997- Organ Systems II: Endothelium, Angiogenesis and Vasculogenesis M.D. Year 1

UCHC

1997- Mech. of Disease: Cardiovascular Pathophysiology M.D. Year 2

UCHC

1997 Frontiers in Basic Sciences M.D. Year 3

UCHC

2000 Eukaryotic Cell Biology, The Nucleus Ph.D. Program

UCHC

2000 Vascular Biology Ph.D. Program

UCHC Course Director

2000-2009 Advances in Signal Transduction Ph.D. Program

UCHC Co-Director

2003-2006 Vascular Biology syllabus for M.D. and D.M.D. curriculum

UCHC Section Head

2007-2009 Cell Biology of Lipid Mediators Graduate Students

UCHC

2010-2016 Pharmacology II Graduate Students

Weill Cornell Graduate School

2011-2016 M.D./Ph.D. Frontiers in Biomedical Research M.D./Ph.D. Students

Weill Cornell Medical College

2012-2016 Lipid Signaling BCMB Graduate Program

Weill Cornell Medical College

2013-2016 Critical Analysis of Literature BCMB Graduate Program

Weill Cornell Graduate School

2013-2016 Cell Biology I, Module II: Cellular Signal Transduction

Weill Cornell Graduate School Director of Module II

2015-2016 Biochemistry Lecture on Cholesterol and Sphingolipids

Weill Cornell Graduate School

2015-2016 G protein / Rho GTPases and the Cytoskeleton M.D. 1st year curriculum

Weill Cornell Graduate School

Formal Teaching of Residents, Clinical Fellows and Research Fellows (post-docs) 1994 Ph.D. Examination, Genetics Program

Patrick Donohue GWU

1995 Ph.D. Examination, Genetics Program Jiangping Shi

GWU

1997 Dissertation Committee Christine Traviss

GWU

1997-2002 Ph.D. Committee UCHC

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Brian Thomson 1998 Ph.D. Examination Committee

Pauline Wong GWU

1999 Ph.D. Qualifying Exam Committee Christy Schilling

UCHC

1999 Ph.D. Committee Robert Smith

UCHC

2002 Ph.D. Committee Ursula Munoz-Najar

UCHC

2003-2009 Ph.D. Committee Susumu Antoku

UCHC

2005-2009 M.D./Ph.D. Thesis Committee Christina Grant

UCHC

2007 Ph.D. Qualifying Examination Committee Zenlong Wang

UCHC

2009-2016 2017

Ph.D. Dissertation Committee Hyejin Choi, Edo Israeli, Dragos Dasoveanu, Peipei Guo, Chaitanya Badwe, Rolake Alibi, Sugev Pandey, Jose Gabriel Barcia Duran Ph.D. Dissertation Committee Ben Andreone, Xavier du Maine

Weill Cornell Medical College Harvard Medical School

Laboratory and Other Research Supervisory and Training Responsibilities

I supervise a laboratory composed of postdoctoral fellows, graduate students, junior faculty members, clinical fellows and research associates/ assistants. I provide overall direction for the projects, design research strategy, review data and run lab meetings. I also provide mentorship for career development of junior scientists. I have recruited and mentored junior faculty since 1998 in both UConn and Weill Cornell.

Formally Supervised Trainees Postdoctoral Trainees 1992-1995 Ari Ristimaki, M.D., Ph.D. / Pathologist; Professor, Helsinki University

(published six manuscripts as a trainee) 1993-1998 Menq-Jer Lee, Ph.D. / Associate Professor, Wayne State University

(published thirteen manuscripts, including a Science paper that “deorphaned” EDG-1 as a receptor for S1P and a Cell paper that described adherens junction regulation, helped him with an AHA scientist development grant and a NIH RO1 which allowed him to get an independent faculty position)

1992-1995 Pazit Ben-Av, Ph.D. / Research Scientist, Bar-Ilan University, Jerusalem, Israel (published four papers on how COX-2 regulates angiogenesis)

1996-2002 Shobha Thangada, Ph.D. / Assistant Professor, University of Connecticut (published 19 papers since 1996 and helped her reach her decision to re-enter Science as a research assistant professor)

1997-2000 David Bishop-Bailey, Ph.D. / Senior Lecturer, University College London (published seven papers during the training period and was rapidly recruited back to the

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William Harvey Institute of University of London) 1997-2001 Nicolas Ancellin, Ph.D. / Senior Scientist, GlaxoSmithKline, Paris

(published 10 papers on S1P receptor pharmacology and demonstrated the role of extracellular sphingosine kinase in angiogenesis)

1997-2002 Ovidiu Trifan, M.D., Ph.D. / Senior Director, Onyx Pharmaceuticals (published seven papers on COX-2 and helped his transition into a pharmaceutical scientist position in Pfizer)

1999-2003 Byeong Churl Jang, Ph.D. / Associate Professor, Keimyung University School of Medicine, Korea (published three papers in the laboratory on the RNA stability of COX-2 and accepted a faculty position in Korea)

2002-2006 Teresa Sanchez, Ph.D. / Assistant Professor, Weill Cornell Medical College (published 11 papers in the laboratory and helped her transition into an independent position by supporting her AHA scientist development grant and a NIH RO1)

2004-2009 Fernando Ferrer, M.D. / Professor of Surgery, Surgeon-in-Chief, University of Nebraska Medical Center and Children’s Hospital, Omahan NE (helped mentor Dr. Ferrer, a urologic surgeon, in biomedical research and vascular biology, served as his KO8 mentor and helped him setup an independent lab which became RO1 funded)

2003-2007 Kirsi Narko, Ph.D. / Scientist, Vanta, Finland (spent time as a pre-doctoral student (1994-1996) and a post-doctoral fellow (2002-2005), during which she published seven papers on COX-2 and cancer)

2004-2009 Krishnan Venkataraman, Ph.D. / Associate Professor, Vellore University, India (published seven papers on sphingosine kinases and assisted in his transition to an Assistant Professor position in India)

2005-2008 Masataka Kohno, M.D., Ph.D. / Associate Professor, Kyoto Prefectural University (published two papers on sphingosine kinases and inflammation and cancer, and returned back to Japan to resume his faculty position and a clinical Rheumatologist)

2006-2010 Myat Lin Oo, M.B.B.S., Ph.D. / Research Associate, Weill Cornell Medical College, Cornell University (published seven papers as a postdoctoral fellow and mentored him as a sponsor during his AHA scientist development grant)

2005-2009 Mallika Ghosh, Ph.D. / Assistant Professor, University of Connecticut (published five papers during her postdoctoral training and transitioned into a research assistant professor position at UConn)

2009-2016 Victoria Blaho, Ph.D. / Assistant Professor, Weill Cornell Medical College (published nine papers as a postdoctoral fellow including a first author paper in Nature. Currently her sponsor for the AHA scientist development grant as she is looking for a position as an Assistant Professor)

2009-2015 Hideru Obinata, Ph.D. / Associate Professor, Gunma University, Japan (published seven papers as a postdoctoral fellow and his work led to the identification of ApoM as a S1P chaperone in HDL.)

2009-2015 Yi-Chien Lu, Ph.D. / Research Scientist, Yale University School of Medicine (published five papers as a postdoctoral fellow including a first author paper on transcriptome-wide identification of miRNA targets in mouse macrophages. Currently working as a research associate in Yale University SOM to get further training)

2009-2015 Marie Sanson, Ph.D., Science Commercialization Officer, France (published a paper as a second author and went into the science commercialization field in

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her home country) 2009-2016 2009-2017 2010-2016 2014-2019 2014-2018

Victoria Blaho, Ph.D., Research Assistant Professor, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA Yuquan Xiong, Ph.D., Research Scientist, Memorial Sloan Kettering Cancer Center, New York, NY Karen Mendelson, Ph.D., Senior Scientist, Mount Sinai Health System, New York, NY Keisuke Yanagida, M.D., Ph.D., Assistant Professor, National Center for Global Research, Tokyo University (Biochemistry), Tokyo, Japan. Yu Hisano, Ph.D., Research scientist, Sumimoto Dainippon Pharmaceutical Co., Osaka, Japan

Ph.D. Students Trained

2003 Kirsi Narko, Ph.D., University of Helsinki (jointly with Ari Ristimaki) (spent 3 years conducting her PhD thesis research in the lab; currently a research scientist in Finland)

2004 Michael Kluk, M.D., Ph.D., University of Connecticut (worked on S1P effects on vascular smooth muscle cells for his PhD thesis; currently a clinical Hem-Onc Pathologist, Weill Cornell Medicine, NY, NY)

2004 Ji-Hye Paik, Ph.D., University of Connecticut (published 12 papers as a graduate student including a first author Molecular Cell and Genes and Development papers; currently an independent faculty member, Tenure-Track Associate Professor, Weill Cornell Medicine, NY, NY)

2004 Sung-Suk Chae, Ph.D., University of Connecticut (published 10 papers as a graduate student including a first author paper in the JCI; currently a research scientist, Institute of Precision Medicine, Weill Cornell Medicine, NY, NY)

2004 Sung-Hee Chang, Ph.D., University of Connecticut (published six papers as a graduate student, following her postdoctoral fellowship at the Beth Israel Hospital/ Harvard Medical School, she returned as an instructor and published 9 additional publications; currently Staff Scientist at Machaon Diagnostics, Oakland, CA)

2008 Athanasia Skoura, Ph.D., University of Connecticut (published 8 papers as a graduate student; currently a Clinical Development Manager at Glaxo Smith Kline, PA)

2009 Cheryl Habrukowich, Ph.D., University of Connecticut (published 2 papers as a graduate student; currently a protein chemist for Beryllium Biotech, Cambridge, MA)

2011 Jason Michaud, M.D., Ph.D., University of Connecticut (published seven papers as a MD/PhD student; currently completing his urology fellowship at Brady Urologic Institute, Johns Hopkins, Baltimore, MD)

2012 Bongnam Jung, Ph.D., Weill Cornell Medical College (published two papers as a graduate student; currently doing a postdoctoral fellowship at the Uppsala University in Sweden)

M.S. Students Trained 1997 Qing Gu, M.Sc., George Washington University

(spent a year doing M.S. thesis research on RNA stability of COX-2) 2008 Flavia Fedeles, M.S., University of Connecticut

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(during her enrollment in the MD/PhD program, Ms. Fedeles decided not to complete her PhD, received the masters degree for her work and is now a Dermatologist in Boston, MA.)

2011-2014 Elizabeth Moskatel, Weill Cornell Medical College (Ms. Moskatel completed her M.S. degree but decided not to continue with her Ph.D. dissertation research)

Local Invited Presentations Those presentations below sponsored by outside entities are so noted and the sponsor(s) is (are) identified. 2003 Center for Regenerative Biology, University of Connecticut, Storrs, CT 2008 Musculoskeletal Research Day, University of Connecticut Health Center 2008 Center for Cell Analysis and Modeling Retreat, University of Connecticut Health Center 2010 Cornell University, School of Veterinary Medicine, Ithaca, NY 2013 University of Connecticut Health Center, Farmington, CT 2013 Pathology Grand Rounds, Weill Cornell Medical College, New York, NY 2016 Vascular Biology Program Retreat, Boston Children’s Hospital, Boston, MA 2017 9th Annual Dr. Judah Folkman Lecture, Boston Children’s Hospital, Boston, MA 2017 Sackler School of Graduate Medical Sciences, Tufts Univ. SOM, Boston, MA Report of Regional, National and International Invited Teaching and Presentations Invited Presentations and Courses Those presentations below sponsored by outside entities are so noted and the sponsor(s) is (are) identified in parentheses. Regional 1996 Yale University School of Medicine, New Haven, CT 1998 Tri-State G-protein Workshop, Mount Sinai Hospital, New York 1998 Center for Molecular Medicine, Maine Medical Center, Portland, ME 1999 Department of Pathology, Weill Cornell School of Medicine, Cornell University, New

York, NY 1999 New York Academy of Sciences meeting on “Bioactive Lipid Signaling”

New York, NY 2000 Bayer, Inc., West Haven, CT (Bayer, Inc.) 2000 Yale University School of Medicine, New Haven, CT 2000 Department of Pharmacology, SUNY at Stony Brook, New York, NY 2000 Hospital for Joint Diseases, NYU School of Medicine, New York, NY 2001 Albany Medical College, Albany, NY 2002 Astra Zeneca, Boston, MA (Astra Zeneca Inc.) 2004 Cornell Medical School, New York, NY 2004 ImClone Systems, New York, NY (Imclone Inc.) 2007 Cardiovascular Department, Merck Research Labs, Rahway, NJ (Merck and Co.) 2007 Vascular Biology Center, Yale University School of Medicine, New Haven, CT 2007 CUNY Graduate School, New York, NY 2008 Abbott Labs, Worcester, MA (Abbott Inc.)

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2008 Weill Cornell Medical College, New York, NY 2008 Department of Pathology, Beth Israel Hospital, Harvard Medical School 2008 Maine Medical Center Research Institute, Portland, ME 2008 New England Immunology Meeting, Cape Cod, MA 2008 SUNY Downstate, Brooklyn, NY 2009 S1P Minisymposium, Biogen IDEC, Boston, MA (Biogen Inc.) 2010 Hospital for Special Surgery, New York, NY 2010 New York Medical College, Valhalla, NY 2010 Visiting Professor, Cardiovascular Research Center, Beth Israel Deaconess Medical

Center, Harvard Medical School 2010 Vascular Biology Seminar Series, Harvard Medical School 2010 Columbia University College of Physicians and Surgeons, New York, NY 2011 Novartis Institute for Biomedical Research, Cambridge, MA (Novartis, Inc.) 2011 NYU Langone Medical Center, Cardiovascular Center, New York, NY 2012 Division of Cardiovascular Medicine, Yale University School of Medicine 2012 Keck Retreat on Biomembranes, Cornell University, Ithaca, NY 2012 New York Lipid and Vascular Biology Club Meeting, Rockefeller University, New York,

NY 2013 Columbia University College of Physicians and Surgeons, New York, NY 2013 Harvard University School of Medicine, Vascular Biology Lectures 2014 Vascular Biology and Therapeutics Program, Yale University School of Medicine, New

Haven, CT 2015 Mount Sinai School of Medicine, Department of Genetics and Developmental Biology,

New York, NY 2016 IVBM 2016, NAVBO, Boston, MA 2016 2016 Boston Angiogenesis Meeting, Boston, MA 2017 2017 2018

The 9th Annual Judah Folkman Lecture, Boston Children’s Hospital, Harvard Medical School, Boston, MA Tufts University Sackler Graduate School of Biomedical Sciences, Boston, MA Center for Excellence in Vascular Biology, Brigham and Women’s Hospital, Boston, MA

National 1992 Keystone Symposia on “The Endothelial Cell,” Keystone, CO 1992 Dupont-Merck, Inc., Wilmington, DE (Dupont-Merck Inc.) 1992 FASEB Annual Meeting, Symposium on “Gene Expression in Endothelial Cells” 1992 Syntex, Inc., Palo Alto, CA (Syntex Inc.) 1992 Miles, Inc., West Haven, CT (Miles Inc.) 1992 Department of Physiology and Biophysics, Georgetown University School of Medicine 1992 Glaxo, Inc., Research Triangle Park, NC (Glaxo Inc.) 1993 Division of Hematology/Oncology, Department of Medicine, Thomas Jefferson University 1993 “Antiinflammatory and Immunosuppressive Drugs,” New York Academy of Sciences 1994 Wyeth-Ayerst, Princeton, NJ (Wyeth-Ayerst Inc.) 1994 Biology, PRI, Johnson and Johnson, Raritan, NJ (Johnson and Johnson, Inc.) 1994 Schering-Plough Corp., Kenilworth, NJ (Schering Plough Inc.) 1994 Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 1995 Inflammatory Diseases Research

Miles, Inc., West Haven, CT (Miles Inc.) 1995 Bristol Myers Squibb, Inc., Seattle, WA (Bristol Myers Inc.)

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1996 Symposium on “Frontiers in Bioactive Lipids” Washington, DC

1996 FASEB Mini Symposium on “Molecular and Cellular Biology of the Vessel Wall” 1997 Department of Biochemistry, The George Washington University, Washington, DC 1997 Arena Pharmaceuticals, San Diego, CA (Arena Pharma Inc.) 1998 Keystone Symposium on the Molecular Biology of the Cardiovascular System 1998 Chair: “Blood Vessel Club,” “Vascular Cell and Molecular Biology”

Experimental Biology Meeting, San Francisco, CA 1998 GTI-Novartis, Inc., Gaithersburg, MD (Novartis Inc.) 1998 Genetics and Biochemistry Branch, NIDDK, NIH 1999 Keystone Symposium on “Inflammatory Paradigms in the Vasculature”

Santa Fe, NM 1999 Keystone Symposium on “Lipid Mediators”

Keystone, CO 1999 “Lysophospholipid Signaling in Mammals”

Experimental Biology Meeting 1999 Novartis Pharma, Inc., Summit, NJ (Novartis, Inc.) 1999 Glaxo Wellcome, Inc., Research Triangle Park, NC (Glaxo, Inc.) 1999 Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 1999 Louisiana State University, Pennington Biomedical Research Center, Baton Rouge, LA 2000 Merck and Co., Rahway, NJ (Merck and Co.) 2000 Department of Pharmacology, UVA, Charlottesville, VA 2000 NIEHS, Research Triangle Park, NC 2000 Genentech, South San Francisco, CA (Genentech Inc.) 2000 University of Pennsylvania School of Medicine, Philadelphia, PA 2001 Gordon Conference on Angiogenesis, Newport, RI 2001 Ceretek, Inc., South San Francisco, CA (Ceretek Inc.) 2001 Pharmacia Corp., St. Louis, MO (Pharmacia Inc.) 2001 Roche, Inc., Nutley, NJ (Roche, Inc.) 2001 Medical College of Wisconsin, Milwaukee, WI 2001 EB 2001 Annual Meeting, Symposium on Lysolipids and Angiogenesis, Orlando, FL 2001 Keystone Symposium on Angiogenesis and Chronic Diseases, Keystone, CO 2001 Keystone Symposium on Eicosanoids, Snowbird, UT 2001 Co-Chair, FASEB Summer Research Conferences on Bioactive Lipids, Phoenix, AZ 2001 Entremed, Inc., Rockville, MD (Entremed Inc.) 2001 Medical University of South Carolina, Charleston, SC 2001 Eicosanoid Meeting, Vanderbilt University, Tennessee 2001 Cox-2 Cancer Meeting, Palm Beach, FL (COX-2 study group) 2001 Cleveland Clinic Foundation Research Institute, Cleveland, OH 2002 Society for Surgical Oncology, Denver, CO 2002 FASEB Summer Research Conference on Phospholipases, Tucson, AZ 2002 Molecular Biology Department, UCLA, Los Angeles, CA 2002 Cox-2 Inhibitors in Oncology, Palm Beach, FL (COX-2 study group) 2003 Gordon Conference on Angiogenesis, Newport, RI 2003 Gordon Conference on Vascular Cell Biology, Ventura, CA 2003 Winter Prostaglandin Meeting, Baltimore, MD 2003 New Jersey Medical and Dental College, Newark, NJ 2003 Novartis Oncology, Summit, NJ (Novartis, Inc.)

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2003 Session Chair, Experimental Biology 2003, San Diego, CA 2003 Pharmacology Department, University of Illinois Medical School, Chicago, IL 2003 Cardiovascular Biology Center, University of North Carolina, Chapel Hill, NC 2003 NIAA, National Institutes of Health, Bethesda, MD 2003 FASEB Summer Conference on Lysophospholipids, Snowmass, CO 2003 Baylor College of Medicine, Woznicki Lecture, Houston, TX 2003 Society for Leukocyte Biology, Plenary Speaker, Philadelphia, PA 2003 Organizer, ASCB Subgroup Meeting on LPA and S1P, San Francisco, CA 2004 City of Hope, Beckman Research Institute, Duarte, CA 2004 University of Tennessee School of Medicine, Memphis, TN 2004 Winter Eicosanoid Meeting, Baltimore, MD 2004 University of Virginia School of Medicine, Charlottesville, VA 2004 NIDA, NIH Symposium on Lipidomics, Washington, DC 2004 Children’s Hospital of Oakland Research Institute, Oakland, CA 2004 Department of Pathology, University of Washington, Seattle, WA 2004 Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 2004 Keynote Speaker, Southern Regional Lipid Conference, Cashiers, NC 2005 Winter Eicosanoid Meeting, Baltimore, MD 2005 NAVBO/ASIP Symposium on Inflammation, EB2005, San Diego, CA 2005 FASEB Summer Conference on Lysolipids, Snowmass, CO 2005 NAVBO Annual Meeting on Vascular Biology, Chicago, IL 2005 Eicosanoid Meeting, San Francisco, CA 2005 American Heart Association Meeting, Dallas, TX 2006 2006

Keynote Speaker, FASEB Summer Conference on Phospholipases, VT Fifth Annual Timberline Symposium on Epithelial Cell Biology-Epithelial Cancer

2006 2006

Gordon Research Conference on Endothelial Cell Phenotypes, ME Experimental Biology 2006 Meeting, San Francisco, CA

2006 Department of Pharmacology, UCSD School of Medicine, San Diego, CA 2006 American Heart Association Annual Meeting, Chicago, IL 2006 Western Illinois University, Macomb, IL 2006 Keynote Speaker, FASEB Summer Conference on Phospolipases 2007 Winter Eicosanoid Meeting, Baltimore, MD 2007 FASEB Summer Meeting on Lysolipids, Tucson, AZ 2007 FASEB Summer Meeting on Lipids and Cancer, Palm Springs, AZ 2007 American Heart Association Annual Meeting, Orlando, FL 2007 Plenary Speaker, Biochemistry and Molecular Biology Annual Meeting 2007 Co-Chair, AACR Frontiers in Cancer Prevention Conference, Philadelphia, PA 2008 Vasculata Course, University of Washington, Seattle, WA 2009 Gordon Conference on Vascular Cell Biology, Ventura, CA 2009 Keystone Meeting on Lipid Signaling, Squaw Creek, CA 2009 Keynote Speaker, FASEB Summer Research Conference on Lysolipids, Carefree, AZ 2010 Gordon Conference on Sphingolipids and Glycolipids, Ventura, CA 2010 Keystone Meeting on Angiogenesis, Keystone, CO 2010 University of North Carolina, Cardiovascular Seminar Series, Chapel Hill, NC 2011 Vascular Cell Biology Gordon Conference, Ventura, CA 2013 University of Pennsylvania, Department of Pharmacology 2013 Yale University / NAVBO Meeting on Lymphatics, New Haven, CT 2013 Medical University of South Carolina, Charleston, SC

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2013 University of California San Diego, Department of Pharmacology, San Diego, CA 2013 American Heart Association 2013 Annual Meeting, Dallas, TX 2013 NAVBO Annual Meeting 2013, Cape Cod, MA 2014 Knight Cardiovascular Center, Oregon Health and Science University, Portland, OR 2014 University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 2014 EB 2014, ASBMB Symposium on Sphingolipids 2015 NICHD, NIH, Bethesda, MD 2015 Vascular Biology Program, Boston Children’s Hospital, Harvard Medical School 2015 MacAllister Heart Institute Student Research Keynote Speaker, University of North

Carolina, Chapel Hill, NC 2015 Cardiovascular Research Center, Northwestern University School of Medicine, Chicago,

IL 2015 University of Pittsburgh School of Medicine, Vascular Biology and Medicine Center,

Pittsburgh, PA 2015 NAVBO 2015, Biology of Signaling in the Cardiovascular System, Hyannis, MA 2015 Visiting Professor, Department of Surgery and Surgical Research Center, University of

Cincinnati School of Medicine, Cincinnati, OH 2016 American Association of University Pathologists (Pluto Society) annual meeting, Vieques, Puerto Rico 2016 Cardiovascular research institute, University of Michigan, Ann Arbor, MI 2016 Arteriosclerosis, Thrombosis, and Vascular Biology/Peripheral Vascular Disease 2016

Scientific Sessions, Nashville, TN 2016 Leducq Scientific Advisory Committee Meeting, Nashville, TN 2016 Frontiers in Science Seminar, Samuel and Jean Frankel Cardiovascular Center at the

University of Michigan, Ann Arbor, MI 2016 LIPID MAPS Annual Meeting, University of California, San Diego, La Jolla, CA 2016 OMRF Research Forum Distinguished Lecturer, Oklahoma Medical Research Foundation,

Oklahoma City, OK 2017 Gordon Research Conference in Vascular Cell Biology, Ventura, CA 2017 Hollings Cancer Center Seminar Series, Charleston, SC 2017 UIC Pharmacology Seminar, Chicago, IL 2017 ASBMB 2017 Annual Meeting, Chicago, IL 2017 Gordon Research Conference in Angiogenesis, Newport, RI 2017 FASEB Summer Research Conference, New Orleans, LA 2017 Lehigh University, Deaprtment of Biological Sciences, Bethlehem, PA 2018 Cardiovascular Biology, Washington University School of Medicine, St. Louis, MO 2018 Cancer Center, Stony Brook University School of Medicine, Long Island, NY 2018 Pathology, Northwestern University School of Medicine, Chicago, IL 2018 North American Vascular Biology Organization, Newport, RI 2018 Medicine, SUNY Downstate, Brooklyn, NY 2018 Cincinnati Children’s Hospital, Concinnati, OH 2019 Gordon Resarch Conference on vascular cell biology, Ventura, CA 2019 Cardiovascular Biology Center, University of Washington, Seattle, WA International 1992 International Society for Heart Research Annual Meeting, Burlington, VT 1993 Mechanisms of Inflammatory Pain

Sandoz Institute /Royal Society, London, U.K. (Sandoz Inc.) 1993 Glaxo Group Research, Greenford, U.K. (Glaxo Inc.)

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1993 Merck-Frosst Center for Therapeutic Research, Montreal, Canada (Merck and Co.) 1993 R.W. Johnson Pharmaceutical Research Institute, Toronto, Canada (Johnson and Johnson

Inc.) 1995 NATO Angiogenesis Meeting, Porto Carras, Greece 1996 Merck-Frosst Research Labs, Montreal, Canada (Merck and Co.) 1997 Tokyo University School of Medicine, Tokyo, Japan 1998 Second International Workshop on Cox-2, Hawaii (COX-2 study group) 1999 G-protein-coupled Receptor Retreat, Merck, Inc., Montreal, Canada (Merck and Co.) 1999 Third International Workshop on Cox-2, Hawaii (COX-2 study group) 1999 Sixth International Conference on Eicosanoids and Other Bioactive Lipids in Cancer,

Inflammation and Related Diseases, Boston, MA 1999 Basic Science Lecturer

Japan Rheumatology Association Annual Meeting, Osaka, Japan 2000 Luncheon Speaker

Japan Atherosclerosis Meeting, Tokyo, Japan 2000 Invited speaker on sphingolipids

Japanese Biochemical Society, Yokohama, Japan 2000 Hanson Center for Biomedical Research, Adelaide, Australia 2001 Seventh International Congress on PAF and Lipid Mediators, Tokyo, Japan 2001 Takeda Science Foundation Symposium, Tokyo, Japan (Takeda Inc.) 2002 Fifth International Conference on Cox-2, Rome, Italy (COX-2 study group) 2003 International Conference on Eicosanoids, Chicago, IL 2004 Sapporo Sphingolipid Symposium, Sapporo, Japan 2004 Gordon Conference on Glycolipids and Sphingolipids, Spring 8, Hyogo, Japan 2004 DFG Meeting on Angiogenesis, Munich, Germany 2004 International Meeting on PAF and Phospholipases, Berlin, Germany 2005 Novartis Meeting on EDG Receptors, Alsace, France (Novartis Inc.) 2005 Keystone Symposium on Lipid Mediators, Whistler, BC, Canada 2005 Angiogenesis Meeting, Ascona, Ticino, Switzerland 2005 Japanese Biochemical Society, Kobe, Japan 2005 Takeda Genome Urology 2005, Kyoto, Japan 2006 Biomedicum Helsinki Seminar Series, Helsinki, Finland 2006 Pharmacology Department, Faculty of Medicine at Siriraj Hospital, Bangkok, Thailand 2006, 2007 Visiting Professor, AEIOU Program for Refugees and Internally Displaced Persons,

Chiang Mai University, Chiang Mai, Thailand 2007 COEP Invited Speaker, Tokyo University, Tokyo, Japan 2007 Biochemistry Department, Chiang Mai University, Thailand 2007 Visiting Professor, Pharmacology Department, Siriraj Hospital, Mahidol University,

Bangkok, Thailand 2007 Invited Keynote Speaker, HHT Foundation International, Capri, Italy 2007 Montreal Eicosanoid Meeting, Montreal, Canada 2007 BMB 2007, Biochemistry and Molecular Biology Society Annual Meeting, Yokohama,

Japan 2008 Gordon Conference on Glycolipids and Sphingolipids, Il Ciocco, Italy 2008 Centenary Institute, Sydney, Australia 2008 International Vascular Biology Meeting, Sydney, Australia 2008 Leopoldina Symposium on Lipid Signaling, Frankfurt, Germany 2008 Kloster Seeon Angiogenesis Meeting, Munich, Germany

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2008 British Pharmacological Society Lysolipid Meeting, London, UK 2009 International Phospholipase Meeting, Tokyo, Japan 2009 Takeda Symposium on Lipid Mediators and Transporters, Tokyo, Japan (Takeda Inc.) 2009 National Cardiovascular Research Center, Osaka, Japan 2009 International Society for Thrombosis and Hemostasis, Boston, MA 2009 Cell Signaling in Cancer, Barossa, South Australia 2010 International Vascular Biology Meeting (IVBM 2010), Los Angeles, CA 2010 Naito Conference on Biomembranes and Lipid Mediators, Sapporo, Japan 2011 European Union League Against Rheumatism Annual Meeting, London, UK 2011 International Society for Thrombosis and Hemostasis 2011, Kyoto, Japan 2011 Second International SFB Symposium “Vascular Differentiation and Remodeling”

Mannheim, Germany 2012 COE Meeting, Kyushu University, Fukuoka, Japan 2012 Rigshospitalet, University of Copenhagen, Denmark 2012 Gordon Research Conference on Sphingolipids, Il Ciocco, Italy 2012 International Vascular Biology Meeting, Wiesbaden, Germany 2012 Cell Symposium on Angiogenesis and Metabolism, Leuven, Belgium (Cell Press, Elsevier) 2012 Molecular Medicine of Sphingolipids, EMBO Meeting, Ramot, Israel 2012 Second ATVB-IF Meeting, Taishan Medical College, Jinan, China 2012 Visiting Professor, Taian Medical College, Shandong Province, China 2012 Department of Medical Research, Lower Myanmar, Yangon, Myanmar 2012 University of Medicine (1), Yangon, Myanmar 2012 University of Medicine (2), Yangon, Myanmar 2013 Uppsala University, Sweden 2013 Karolinska Institute, Stockholm, Sweden 2013 FASEB Summer Research Conference on Lysophospholipids, Sapporo, Japan 2013 University of Tokyo, Global Health Research Institute, Tokyo, Japan 2013 Juntendo University, Lipid Research Institute, Tokyo, Japan 2013 Inserm Paris, Cardiovascular Research Center, Pompedou Hospital, Paris, France 2014 International Vascular Biology Meeting, Kyoto, Japan 2014 Visiting Professor, Duke/NUS School of Medicine, Singapore 2014 Gordon Research Conference in Endothelial Phenotypes, Barcelona, Spain 2014 Lipid Mediators in Health and Disease, Karolinska Institute, Stockholm, Sweden 2014 Kloster Seeon Meeting on Angiogenesis, Munich, Germany 2014 Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany 2014 Molecular Medicine of Sphingolipids, EMBO Conferences

Kloster Banz, Franconia, Germany 2015 Phospholipase and Lipid Mediators Meeting, Tokyo, Japan 2015 Eicosanoid Research Foundation Annual Meeting, Budapest, Hungary 2015 Gordon Conference on Biomaterials and Tissue Engineering, Girona, Spain 2015 FASEB Summer Research Conference on Lysolipid Mediators, Banff, Canada 2015 Dies Academicus, Goethe University Faculty of Medicine, Frankfurt, Germany 2016 Gordon conference on glycolipids and sphingolipids, Il Ciocco, Italy 2016 PLUTO Society Meeting, American Association of University Pathologists, Vieques Island,

Puerto Rico 2016 RIKEN IMS Summer Program (RISP) 2016, Yokohama, Japan 2016 Gordon Research Conference, Endothelial Cell Phenotypes in Health & Disease, Girona,

Spain

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2016 SphingoNet Summer Meeting. Fondation Leducq, Sweden 2016 CRC1123 International Symposium, Atherosclerosis –Mechanisms and novel therapeutic

targets, Nymphenburg Palace, Munich 2017 PLUTO Society Meeting, American Association of University Pathologists, Panama City,

Panama 2017 7th Meeting of the French Angiogenesis Society, Toulouse, FR 2017 International Society on Thrombosis and Haemostasis (ISTH) 2017, Berlin, Germany 2017 Japanese Society for Inflammation and Regenration, Osaka, Japan (Keynote) 2017 Kitasato University School of Medicine, Tokyo, Japan 2017 58th International Conference on the Bioscience of Lipids, Zurich, Switzerland 2017 Novartis Institutes for Biomedical Research, Basel, Switzerland 2017 ONO's 300th Anniversary Symposium, Tokyo, Japan 2017 Department of Pharmaceutical Sciences, Tohuku University, Sendai, Japan 2017 International Conference on Lipoquality, Tokyo, Japan 2017 Astellas Pharma, Tsukuba, Japan 2018 PLUTO Society Meeting, American Association of University Pathologists, St. Kitts-Nevis 2018 International Vascular Biology Meeting ’18; Helsinki, Finland 2018 International Union of Pharmacology annual meeting, Kyoto, Japan 2018 Kitasato University Froum, Tokyo, Japan 2018 Gordon research conference on endothelial cell phenotypes, Lucca, Barga, Italy 2018 European meeting on lipid mediators, Brussels, Belgium Report of Technological and Other Scientific Innovations

November 23, 2010

Methods of inhibiting vascular permeability and apoptosis US PTO-7,838,562

March 14, 2017 Endothelium protective materials and methods of use

US PTO- 9,592,268

August 15, 2016 Engineered sphingosine 1-phosphate (S1P) chaperone protein compositions and methods for treating vascular and non-vascular diseases and conditions

US PTO-US62375088 August 15, 2017 ApoM-Fc Fusion proteins and uses thereof. USPTO – provisional application March 2018 S1PR2 functional antagonists for the treatment of fibrosis and pathological

angiogenesis

Educational Material for Patients and the Lay Community

Books, monographs, articles and presentations in other media No educational materials below were sponsored by outside entities 2005 A balanced look at

COX-2 drugs Op. Ed., Boston Globe March 25, 2005

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Report of Scholarship Publications

Peer reviewed publications in print or other media

Research Investigations: 1. Bailey, J.M., Muza, B., Hla, T. and Salata, K. (1985) Restoration of prostacyclin synthase in

vascular smooth muscle cells after aspirin treatment: regulation by epidermal growth factor. J. Lipid Res., 26:54-61.

2. Gorodetsky, G., Hla, T. and Bailey, J.M. (1985) Recovery of prostacyclin synthesis in human vascular endothelial cells following intermittent or continuous exposure to indomethacin. Pharm. Res. Comm., 17 (5):447-456.

3. Hla, T., Farrell, M., Kumar, A. and Bailey, J.M. (1986) Isolation of the cDNA for human Prostaglandin H Synthase. Prostaglandins, 32:829-846.

4. Siegall, C.B., Hla, T., and Kumar, A. (1988) Reconstituted U1 Small Nuclear Ribonucleoprotein Complex Restores 5' Splice-Site Cleavage Activity. Biochem. Biophys. Res. Comm., 154:1010-1017.

5. Hla, T. and Bailey, J.M. (1989) Differential recovery of Prostacyclin synthesis in endothelial cells versus smooth muscle cells following inactivation of cyclooxygenase with aspirin. Pros. Leuk. Essent. Fatty Acids, 36:175-184.

6. Goldgaber, D., Harris, H.W., Hla, T., Maciag, T., Donnelly, R.J., Jacobsen, J.S., Vitek, M.P., Guiroy, M.P. and Gajdusek, D.C. (1989) Interleukin-1 Regulates the Synthesis of Amyloid b-Protein Precursor mRNA in Human Endothelial Cells. Proc. Natl. Acad. Sci., USA, 86:7606-7610.

7. Hla, T. and Maciag, T. (1990) Isolation of Unique, Immediate Early Differentiation mRNAs by Enzymatic Amplification of Subtracted cDNA from Human Endothelial Cells. Biochem. Biophys. Res. Comm., 167:637-643.

8. Hla, T. and Maciag, T. (1990) An Abundant Transcript Induced In Differentiating Human Endothelial Cells Encodes a Polypeptide with Structural Similarities to G-Protein-Coupled Receptors. J. Biol. Chem., 265:9308-9313.

9. Maier, J.A.M., Hla, T. and Maciag, T. (1990) Cyclooxygenase is an Immediate-Early Gene Induced by Interleukin-1 in Endothelial Cells. J. Biol. Chem., 265:10805-10808.

10. Imamura, T., Engleka, K., Zhan, X., Tokita, Y., Forough, R., Roeder, D., Jackson, A., Maier, J., Hla, T. and Maciag, T. (1990) Addition of Nuclear Translocation Sequence Reconstitutes the Mitogenic Activity of a Growth Factor Mutant. Science 249:1567-1570.

11. Remmers, E., Sano, H., Lafyatis, R., Case, J., Kumkumian, G., Hla, T., Maciag, T. and Wilder, R. (1991) Production of Platelet Derived Growth Factor B Chain (PDGF-B/ c-sis) mRNA and Immunoreactive PDGF B-like Polypeptide by Rheumatoid Synovium: Coexpression with Heparin Binding Acidic Fibroblast Growth Factor-1. J. Rheumatol. 18:7-13.

12. Siegall, C.B., Epstein, S., Spier, E., Hla, T., Forough, R., Maciag, T., Fitzgerald, D. J., and Pastan, I. (1991) Cytotoxic Activity of Chimeric Proteins Composed of Acidic Fibroblast Growth Factor and Pseudomonas Exotoxin on a Variety of Cell Types. FASEB J. 5:2843-2849.

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13. Hla, T.and Maciag, T. (1991) Cyclooxygenase gene expression is down-regulated by heparin-binding (acidic fibroblast) growth factor in Human endothelial cells. J. Biol. Chem. 266:24059-24063.

14. Sano, H., Hla, T., Maier, J., Crofford, L., Case, J., Maciag, T. and Wilder, R. (1992) In vivo Cyclooxygenase Expression in Synovial Tissues of Patients with Rheumatoid Arthritis and Osteoarthritis and Rats with Adjuvant and Streptococcal Cell Wall Arthritis. J. Clin. Invest. 89:97-108.

15. Hla, T.and Neilson, K. (1992) Human Cyclooxygenase-2 cDNA. Proc. Natl. Acad. Sci., USA. 89:7384-7388.

16. Sano, H., Engleka, K., Mathern, P., Hla, T., Crofford, L., Remmers, E., Jelsema, C., Goldmuntz, E., Maciag, T. and Wilder, R. L. (1993) Coexpression of Phosphotyrosine-Containing Proteins, PDGF-B and FGF-1 in situ in Synovial Tissues of Patients with Rheumatoid Arthritis and Lewis Rats with Streptococcal Cell Wall Arthritis. J. Clin. Invest. 91:553-565.

17. Crofford, L.J., Wilder, R.L., Ristimäki, A., Remmers, E., Epps, H.R. and Hla, T. (1994) Cyclooxygenase-1 and -2 expression in Rheumatoid Synovial Tissues: Effects of Interleukin-1b, Phorbol Myristic Acetate, and Corticosteroids. J. Clin. Invest. 93, 1095-1101.

18. Ristimäki, A., Garfinkel, S., Wessendorf, J., Maciag, T. and Hla, T.(1994) Induction of Cyclooxygenase-2 by Interleukin-1a : Evidence for post-transcriptional regulation. J. Biol. Chem. 269, 11769-11775.

19. Appleby, S.B., Ristimäki, A., Neilson, K., Narko, K. and Hla, T.(1994) Structure of the Human Cyclooxygenase-2 Gene. Biochem. J. 302, 723-727.

20. Laneuville, O., Breuer, D.K., DeWitt, D.L., Hla, T., Funk, C.D. and Smith, W.L. (1994) Differential Inhibition of Human Prostaglandin H Synthases-1 and -2 by Non-steroidal Anti-inflammatory Drugs. J.Pharm.Exper.Ther. 271, 927-934.

21. Hla,T., Jackson, A.Q., Appleby, S.B. and Maciag, T. (1995) Characterization of edg-2, a human homologue of the Xenopus maternal transcript G10. Biochim. Biophys. Acta 1260, 227-229.

22. Sano, H., Kawahito, Y., Wilder, R.L., Hashiramoto, A., Mukai, S., Asai, K., Kimura, S., Kato, H., Kondo, M. and Hla, T. (1995) Expression of Cyclooxygenase-1 and -2 in Colorectal Cancer. Cancer Res. 55, 3785-3789.

23. Ben-Av, P., Crofford, L.J., Wilder, R.L. and Hla, T. (1995) Vascular Endothelial Cell Growth Factor is Induced by Inflammatory Mediators Prostaglandin E2 and Interleukin-1 in Rheumatoid Synovial Fibroblasts. FEBS Letters. 372, 83-87.

24. Hla, T.(1996) Characterization of the 5.2 kb Transcript Isoform of Cyclooxygenase-1. Prostaglandins 51(1), 81-85.

25. Ristimäki, A., Narko, K. and Hla, T. (1996) Down-Regulation of Cytokine-Induced Cyclooxygenase-2 Transcript Isoforms by Dexamethasone: Evidence for Post-Transcriptional regulation. Biochem. J. 318, 325-331.

26. Lee, M-J., Evans, M., and Hla, T. (1996) The Inducible G-Protein-Coupled Receptor edg-1 Signals Via the Gi / MAP Kinase Pathway. J. Biol. Chem. 271, 11272-11279.

27. Crofford, LJ, Tan, B., McCarthy, CJ, and Hla, T. (1997) Involvement of NF-kB in the regulation of Cyclooxygenase-2 Expression by Interleukin-1 in Rheumatoid Synoviocytes. Arth. and Rheumatism. 40, 226-236.

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28. Liu, C.H. and Hla, T. (1997) The mouse gene for the Inducible G-protein-coupled receptor edg-1. Genomics 43, 15-24.

29. Narko, K., Ristimaki, A., MacPhee, M., Smith, E. and Haudenschild, CC, Hla, T.(1997) Tumorigenic Transformation of Immortalized ECV Endothelial Cells by Cyclooxygenase-1 Over-expression. J. Biol. Chem. 272(34). 21455-21461.

30. Hla, T. , Zimrin, A., Evans, M., Ballas, K. and Maciag, T. (1997) The immediate-early gene product MAD-3/edg-3/IkBa is an endogenous regulator of FGF-1-induced human endothelial cell growth. FEBS Letters. 414, 419-424.

31. Gou, Q., Liu, C.H., Ben-Av, P. and Hla, T. (1998) Dissociation of basal turnover and cytokine-induced transcript stabilization of the human cyclooxygenase-2 mRNA by mutagenesis of the 3’-untranslated region. Biochem. Biophys. Res. Comm. 242, 508-512.

32. Hida, T., Makheja, A., Ben-Av, P., Hla, T., Martinez, A., Leyton, J., Mulshine, J. and Moody, T.W. (1998) Non-small cell lung cancer cycloxygenase activity and proliferation are inhibited by non-steroidal antiinflammatory drugs. Anticancer Research 18, 775-782.

33. Lee, MJ, Van Brocklyn, JR, Thangada, S, Liu, CH, Hand, AR , Menzeleev, R, Spiegel, S and Hla, T. (1998) Sphingosine-1-phosphate as a ligand for the G-protein-coupled receptor EDG-1. Science 279, 1552-1556.

34. Van Brocklyn, JR, Lee, MJ, Menzeleev, R, Olivera, A, Edsall, L, Cuvillier, O, Thomas, DM, Coopman, PJP, Thangada, S, Liu, C.H., Hla, T. and Spiegel, S (1998) Dual actions of sphingosine-1-phosphate: Extracellular through the orphan Gi-coupled receptor edg-1 and intracellular to regulate proliferation and survival. J. Cell Biol.142:229-240.

35. Lee, MJ, Thangada, S, Liu, CH, Thompson, BD, and Hla, T. (1998) Lysophosphatidic acid activates the G-protein coupled receptor EDG-1 as a low affinity agonist. J. Biol. Chem. 273: 22015-22112.

36. Liu, CH, Thangada, S, Lee, M-J, Van Brocklyn, JR, Spiegel, S and Hla, T. (1999) Ligand-induced trafficking of the Sphingosine-1-phosphate receptor EDG-1. Mol. Biol. Cell. 10, 1179-1190.

37. Bishop-Bailey, D and Hla, T.(1999) Endothelial cell apoptosis induced by the PPARg ligand 15-deoxy-∆12,14 prostaglandin J2. J. Biol. Chem. 274, 17042-17048.

38. Ancellin, N. and Hla, T. (1999) Differential pharmacological properties and signal transduction of the sphingosine-1-phosphate receptors EDG-1, EDG-3 and EDG-5. J. Biol. Chem. 274, 18997-19002.

39. Trifan, O.C., Smith, R. , Thompson, B.D. and Hla, T. (1999) Overexpression of cyclooxygenase-2 induces cell-cycle arrest: evidence for a prostaglandin-independent mechanism. J. Biol. Chem. 274 (48), 34141-34147.

40. Windh, RT, Lee, M-J, Hla, T., An, S, Barr, AJ, and Manning, DR (1999) Differential coupling of sphingosine-1-phosphate receptors EDG-1, EDG-3 and H218/EDG-5 to the Gi, Gq and G12 families of heterotrimeric G proteins. J. Biol. Chem. 274(39), 27351-27358.

41. Lee, M., Thangada, S., Claffey, K.P., Ancellin, N., Liu, C.H., Kluk, M., Volpi.. M., Sha’afi, R.I. and Hla, T. (1999) Vascular endothelial cell adherens junction assembly and morphogenesis induced by sphingosine-1-phosphate. Cell 99 (3), 301-312.

42. Yamada, R., Sano, H., Hla, T., Hashiramoto, A., Fukui, W., Miyazaki, S., Tsubouchi, Y., Kusaka, Y. and Kondo, M. (1999) Auranofin selectively inhibits the transcript of cyclooxygenase-2 through

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the inhibition of NF-kB and directly inhibits proliferation of cultured rheumatoid synoviocytes. Eur. J. Pharm. 385, 71-79.

43. Clark, RB, Bishop-Bailey, D, Estrada-Hernandez, T, Hla, T., Puddington, L, and Padula, SJ (2000) The nuclear receptor PPAR gamma and immunoregulation: PPAR gamma mediates inhibition of helper T cell responses. J. Immuno. 164: 1364-1371.

44. Im, D-S, Heise, CE, Ancellin, N, O’Dowd, B, Shei, G, Heavens, R, Rigby, M, Hla, T., Mandala, S, McAllister, G, George, S, and Lynch, KR (2000) Characterization of a novel sphingosine-1 phosphate receptor EDG-8. J. Biol. Chem. 275(19) 14281-14286.

45. Yamada, R., Sano, H., Hla, T., Hashiramoto, A., Fukui, W., Miyazaki, S., Kohmo, M., Tsubouchi, Y., Inoue, M., Komatsu, A. and Kondo, M. (2000) Selective inhibition of cyclooxygenase-2 with antisense oligonucleotide restricts induction of rat adjuvant-induced arthritis. Biochem. Biophys. Res. Commun. 269(2):415-21.

46. Tsubouchi Y, Sano H, Kawahito Y, Mukai S, Yamada R, Kohno M, Inoue Ki, Hla T., Kondo M. (2000) Inhibition of Human Lung Cancer Cell Growth by the Peroxisome Proliferator-Activated Receptor-gamma Agonists through induction of Apoptosis. Biochem Biophys Res Commun. 270(2):400-405.

47. Yoshimura R, Sano H, Masuda C, Kawamura M, Tsubouchi Y, Chargui J, Yoshimura N, Hla T., Wada S. (2000) Expression of cyclooxygenase-2 in prostate carcinoma. Cancer. 2000 Aug 1;89(3):589-96.

48. Kawahito, Y., Kondo, M., Hashiramoto, A., Bishop-Bailey, D., Inoue, K., Kohno, M., Tsubouchi, Y., Yamada, R., Mukai, S., Hla, T. and Sano. H. (2000) PPAR-g ligands induce apoptosis of rheumatoid synoviocytes and suppress adjuvant-induced arthritis in rats. J. Clin. Invest. 106(2):189-97.

49. Liu, Y., Wada, R, Yamashita, T., Mi, Y., Deng, C-X, Hobson, J. P., Rosenfeldt, H.M., Nava, V.E., Chae, S., Lee, M.J., Liu, C.H., Hla, T., Spiegel, S. and Proia, R.L. (2000) Edg-1, the G-protein-coupled receptor for sphingosine-1-phosphate, is essential for vascular maturation. J. Clin. Invest. 106, 951-961.

50. Jang, B-C, Sanchez, T, Schaefers, HJ, Trifan, OC, Creminon, C., Liu, CH, Huang, C-K, and Hla, T. (2000) Serum withdrawal-induced post-transcriptional stabilization of cyclooxygenase (COX)-2 mRNA in MDA-MB-231 mammary carcinoma cells requires the activity of the p38 stress-activated protein (SAP) kinase. J. Biol. Chem. 275(50):39507-15.

51. Bishop-Bailey D, Hla T., Warner TD. (2000) Bisphenol A diglycidyl ether (BADGE) is a PPARgamma agonist in an ECV304 cell line. Br J Pharmacol. 131, 651-654.

52. Paik, Ji H, Chae, Sungsuk, Lee, Menq-Jer, Thangada, Shobha and Hla, T. (2001) Sphingosine-1-phosphate induced endothelial cell migration requires the expression of EDG-1 and EDG-3 receptors and Rho-dependent activation of av b3 and b 1-containing integrins. J. Biol. Chem. 276, 11830-11837.

53. Casibang M, Purdom S, Jakowlew S, Neckers L, Zia F, Ben-Av P, Hla T., You L, Jablons DM, Moody TW. Prostaglandin E(2) and vasoactive intestinal peptide increase vascular endothelial cell growth factor mRNAs in lung cancer cells. Lung Cancer. 2001 Mar;31(2-3):203-212.

54. Liu, C. H., Chang, Sung-Hee, Trifan, O. C., Narko, K., Smith, E., Haudenschild, C., Lane, T. F. and Hla, T. (2001) Over-expression of cyclooxygenase (Cox)-2 gene is sufficient to induce tumorigenesis in transgenic mice. J. Biol. Chem. 276, 18563-18569.

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55. Morales-Ruiz, M., Lee, M.-J.,, Zöllner, S., Gratton, J.-P., Scotland, R., Shiojima, I., Walsh, K., Hla, T., and Sessa, W.C. (2001) Sphingosine-1-phosphate activates Akt, nitric oxide production and chemotaxis through a Gi -protein/ phosphoinositide 3-kinase pathway in endothelial cells. J. Biol. Chem. 276, 19672-19677.

56. Tsubouchi Y, Kawahito Y, Kohno M, Inoue Ki, Hla T, Sano H. (2001) Feedback control of the arachidonate cascade in rheumatoid synoviocytes by 15-deoxy-delta(12,14)-prostaglandin J2. Biochem Biophys Res Commun 283(4):750-755.

57. Lee, M-J., Thangada, S., Paik, JH, Sapkota, GP, Ruiz, MM, Ancellin, N, Wu, M-T, Sessa, WC, Alessi, D, Hla, T. (2001) Akt mediated phosphorylation of the G-protein-coupled receptor EDG-1 is required for endothelial cell chemotaxis. Molecular Cell 8, 693-704.

58. Kluk, M. and Hla, T. (2001) Role of the Sphingosine 1-phosphate Receptor EDG-1 in vascular smooth muscle cell proliferation and migration. Circ. Res. 89, 496-502.

59. Ancellin, N., Colmont, C., Su, J., Li, Q., Steffansson, S., Liau, G. and Hla, T. (2002) Extracellular export of sphingosine kinase-1 enzyme : Sphingosine 1-phosphate generation and the induction of angiogenic vascular maturation. J. Biol. Chem. 277, 6667-6675.

60. Bishop-Bailey D, Hla T, Warner TD. (2002) Intimal smooth muscle cells as a target for peroxisome proliferator-activated receptor-gamma ligand therapy. Circ. Res. 91(3):210-7

61. Jang, B.-J. and Hla, T. (2002) Regulation of expression and potential carcinogenic role of Cox-2. in COX-2 blockade in cancer prevention and therapy. Ed. R.E. Harris. Humana Press NJ. pp. 171-184.

62. Kluk, MJ, Colmont, C, Wu, M-T and Hla, T. (2003) Platelet Derived Growth Factor (PDGF)-induced Chemotaxis does not require the G-protein-coupled receptor S1P1 in murine embryonic fibroblasts and vascular smooth muscle cells. FEBS Letters 533: 25-28.

63. Jang, B.-J., Munoz-Najar, U., Paik, J.-H., Claffey,K. Yoshida, M., and Hla, T. (2003) Leptomycin B, an inhibitor of the nuclear export receptor CRM1, inhibits COX-2 expression. J. Biol. Chem. 278(5):2773-6.

64. Donohue PJ, Richards CM, Brown SA, Hanscom HN, Buschman J, Thangada S, Hla T., Williams MS, Winkles JA. (2003) TWEAK Is an Endothelial Cell Growth and Chemotactic Factor That Also Potentiates FGF-2 and VEGF-A Mitogenic Activity. Arterioscler Thromb Vasc Biol. Feb 20

65. Inaba T, Sano H, Kawahito Y, Hla T., Akita K, Toda M, Yamashina I, Inoue M, Nakada H. (2003) Induction of cyclooxygenase-2 in monocyte/macrophage by mucins secreted from colon cancer cells. Proc Natl Acad Sci U S A. 100(5):2736-41.

66. Sengupta S, Jang BC, Wu MT, Paik JH, Furneaux H, Hla T.(2003) The RNA-binding protein HuR regulates the expression of cyclooxygenase-2. J Biol Chem. 278, 25227-25233.

67. Sanchez, T., Estrada-Hernandez, T., Paik, J.H., Wu, M., Venkataraman, K., Brinkmann, V., Claffey, K. Hla, T. (2003) Phosphorylation and action of the immunomodulator FTY720 inhibits VEGF-induced vascular permeability. J. Biol. Chem 278, 47281-47290

68. Erkinheimo, T., Lassus, H., Sivula, A., Sengupta, S., Furneaux, H., Hla, T., Haglund, C., Butzow, R. and Ristimäki, A. (2003) Cytoplasmic HuR Expression Correlates with Poor Outcome and with Cyclooxygenase 2 Expression in Serous Ovarian Carcinoma. Cancer Res. 63: 7591-7594.

69. Sung-Hee Chang, Catherine H. Liu, Rebecca Conway, David K. Han, Kasem Nithipatikom, Ovidiu C. Trifan, Timothy F. Lane and Hla, T. (2004) Role of PGE2-dependent Angiogenic Switch in COX-2-induced Breast Cancer Progression. Proc. Natl. Acad. Sci., USA 101(2):591-6

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70. Chae, S., Paik, J., Allende, M.L., Proia, R.L. and Hla, T. (2004) Regulation of limb development by the sphingosine 1-phosphate receptor S1p1/ EDG-1 occurs via the hypoxia/ VEGF axis. Developmental Biology 268: 441-447

71. Chae, S., Proia, RL and Hla, T. (2004) Constitutive Expression of the S1P1 receptor in adult tissues. Prostaglandins and Other Lipid Mediators 73(1-2):141-50

72. Ji-Hye Paik, Athanasia Skoura, Sung-Suk Chae, Ann E. Cowan, David K. Han, Richard L. Proia and Hla, T. (2004) Sphingosine 1-phosphate receptor regulation of N-cadherin mediates vascular stabilization. Genes and Development. 2004 Oct; 18(19): 2392-2403.

73. Chae, SS, Paik, JH, Furneaux, H and Hla, T. (2004) Requirement for sphingosine 1-phosphate receptor-1 in tumor angiogenesis demonstrated by in vivo RNA interference. J. Clin. Invest. 2004 Oct; 114(8): 1082-1089.

74. Knostman KA, Cho JY, Ryu KY, Lin X, McCubrey JA, Hla T, Liu CH, Di Carlo E, Keri R, Zhang M, Hwang DY, Kisseberth WC, Capen CC, Jhiang SM. Signaling through 3',5'-cyclic adenosine monophosphate and phosphoinositide-3 kinase induces sodium/iodide symporter expression in breast cancer. J Clin Endocrinol Metab. 2004 Oct;89(10):5196-203.

75. Li Z, Dong X, Wang Z, Liu W, Deng N, Ding Y, Tang L, Hla T., Zeng R, Li L, Wu D., (2005) Regulation of PTEN by Rho small GTPases., Nat Cell Biol. Apr;7(4):399-404. Epub 2005 Mar 27.

76. Heinonen M, Bono P, Narko K, Chang SH, Lundin J, Joensuu H, Furneaux H, Hla, T., Haglund C, Ristimaki A., (2005) Cytoplasmic HuR expression is a prognostic factor in invasive ductal breast carcinoma. Cancer Res. Mar 15;65(6):2157-61.

77. Sanchez T, Thangada S, Wu MT, Kontos CD, Wu D, Wu H, Hla T., (2005) PTEN as an effector in the signaling of antimigratory G protein-coupled receptor. Proc Natl Acad Sci U S A. Mar 22;102(12):4312-7. Epub 2005 Mar 11.

78. Lepley D, Paik JH, Hla T., Ferrer F. (2005) The G protein-coupled receptor S1P2 regulates Rho/Rho kinase pathway to inhibit tumor cell migration. Cancer Res. 2005 May 1;65(9): 3788-95.

79. Li Z, Paik JH, Wang Z, Hla T, Wu D. (2005) Role of guanine nucleotide exchange factor P-Rex-2b in sphingosine 1-phosphate-induced Rac1 activation and cell migration in endothelial cells. Prostaglandins Other Lipid Mediat. 2005 May;76(1-4):95-104.

80. Jo E, Sanna MG, Gonzalez-Cabrera PJ, Thangada S, Tigyi G, Osborne, DA, Hla T, Parrill AL, Rosen H. (2005) S1P(1)-Selective In Vivo-Active Agonists from High-Throughput Screening: Off-the-Shelf Chemical Probes of Receptor Interactions, Signaling, and Fate. Chem Biol. 2005 Jun:12(6):703-15.

81. Chang SH, Ai Y, Breyer RM, Lane TF, Hla T. (2005) The prostaglandin E2 receptor EP2 is required for cyclooxygenase 2-mediated mammary hyperplasia. Cancer Res. 2005 Jun 1;65(11):4496-9.

82. Chang, SH, Liu, CH, Wu, Ming-Tao, Hla, T. (2005) Regulation of vascular endothelial cell growth factor expression in mouse mammary tumor cells by the EP2 subtype of the Prostaglandin E2 receptor. Prostaglandins and Other Lipid Mediators May;76(1-4):48-58. Epub 2005 Mar 17.

83. Howe LR, Chang SH, Tolle KC, Dillon R, Young LJ, Cardiff RD, Newman RA, Yang P, Thaler HT, Muller WJ, Hudis C, Brown AM, Hla T, Subbaramaiah K, Dannenberg AJ. (2005) HER2/neu-induced mammary tumorigenesis and angiogenesis are reduced in cyclooxygenase-2 knockout mice. Cancer Res. Nov 1;65(21):10113-9.

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84. LaMontagne K, Littlewood-Evans A, Schnell C, O'Reilly T, Wyder L, Sanchez T, Probst B, Butler J, Wood A, Liau G, Billy E, Theuer A, Hla T, Wood J. (2006) Antagonism of sphingosine-1-phosphate receptors by FTY720 inhibits angiogenesis and tumor vascularization. Cancer Res. Jan 1;66(1):221-31.

85. Lee JF, Ozaki H, Zhan X, Wang E, Hla T, Lee MJ. (2006) Sphingosine-1-phosphate signaling regulates lamellipodia localization of cortactin complexes in endothelial cells. Histochem Cell Biol. Jan 14;:1-8

86. Kitano M, Hla T, Sekiguchi M, Kawahito Y, Yoshimura R, Miyazawa K, Iwasaki T, Sano H. Saba JD, Tam YY. (2006) Sphingosine 1-phosphate/sphingosine 1-phosphate receptor 1 signaling in rheumatoid synovium: regulation of synovial proliferation and inflammatory gene expression. Arthritis Rheum. Mar;54(3):742-53.

87. Venkataraman, K., Thangada, S, Michaud, J., Oo, ML, Ai, Y, Lee, YM, wu, MT, Parikh, N, Khan, F, Proia, Rl and Hla, T. (2006) Extracellular Export of sphingosine kinase-1a contributes to the vascular S1P gradient. Biochem J. 397(3):461-71.

88. Subbaramaiah K, Howe LR, Port ER, Brogi E, Fishman J, Liu CH, Hla T, Hudis C, Dannenberg AJ. (2006) HER-2/neu status is a determinant of mammary aromatase activity in vivo: evidence for a cyclooxygenase-2-dependent mechanism. Cancer Res. May 15;66(10):5504-11.

89. Michaud, J, Kohno, M., Proia, RL and Hla, T. (2006) Normal acute and chronic inflammatory responses in sphingosine kinase-1 knock-out mice. FEBS Letters 580(19):4607-12. Epub 2006 Jul 21.

90. Lee JF, Zeng Q, Ozaki H, Wang L, Hand AR, Hla T, Wang E, Lee MJ. (2006) Dual roles of tight junction associated protein, zonula occludens-1, in sphingosine-1-phosphate mediated endothelial chemotaxis and barrier integrity.J Biol Chem. 2006 Aug 6; [Epub ahead of print]

91. Thompson B, Ancellin N, Fernandez SM, Hla T, Sha'afi RI. Protein kinase Calpha and sphingosine 1-phosphate-dependent signaling in endothelial cell. (2006) Prostaglandins Other Lipid Mediat. 2006 Jul;80(1-2):15-27. Epub 2006 Jul 7.

92. Kohno, M, Momoi, M, Oo, ML, Paik, JH, Lee, YM, Venkataraman, K, Ai, Y, Ristimaki, AP, Fyrst, H, Sano, H, Rosenberg, D, Saba, JD, Proia, RL, Hla, T. (2006) An intracellular role for Sphingosine Kinase 1 in intestinal adenoma cell proliferation Mol. Cell. Biol. Oct;26(19):7211-23.

93. Sanchez T, Skoura A, Wu MT, Casserly B, Harrington EO, Hla T. (2007) Induction of Vascular Permeability by the Sphingosine-1-Phosphate Receptor-2 (S1P2R) and its Downstream Effectors ROCK and PTEN. Arterioscler Thromb Vasc Biol. 2007 Jun;27(6):1312-8.

94. Kono M, Belyantseva IA, Skoura A, Frolenkov GI, Starost MF, Dreier JL, Lidington D, Bolz SS, Friedman TB, Hla T, Proia RL. Deafness and Stria Vascularis Defects in S1P2 Receptor-null Mice. J Biol Chem. 2007 Apr 6;282(14):10690-6. Epub 2007 Feb 6.

95. Oo ML, Thangada S, Wu MT, Liu CH, Macdonald TL, Lynch KR, Lin CY, Hla T. Immunosuppressive and anti-angiogenic sphingosine 1-phosphate receptor-1 agonists induce ubiquitinylation and proteasomal degradation of the receptor. J Biol Chem. 2007 Mar 23;282(12):9082-9. Epub 2007 Jan 21.

96. Gonzalez-Cabrera PJ, Hla T, Rosen H. Mapping pathways downstream of sphingosine 1-phosphate subtype 1 by differential chemical perturbation and proteomics. J Biol Chem. 2007 Mar 9;282(10):7254-64. Epub 2007 Jan 10.

97. Ghosh M, Wang H, Ai Y, Romeo E, Luyendyk JP, Peters JM, Mackman N, Dey SK, Hla T.

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COX-2 suppresses tissue factor expression via endocannabinoid-directed PPAR{delta} activation. J Exp Med. 2007 Sep 3;204(9):2053-61.

98. Skoura A, Sanchez T, Claffey K, Mandala SM, Proia RL, Hla T. Essential role of sphingosine 1-phosphate receptor 2 in pathological angiogenesis of the mouse retina. J Clin Invest. 2007 2007 Sep;117(9):2506-16.

99. Soldi R, Mandinova A, Venkataraman K, Hla T, Vadas M, Pitson S, Duarte M, Graziani I, Kolev V, Kacer D, Kirov A, Maciag T, Prudovsky I. Sphingosine kinase 1 is a critical component of the copper-dependent FGF1 export pathway. Exp Cell Res. 2007 Sep 10;313(15):3308-18. Epub 2007 Jul 6.

100. Lee, YM Venkataraman K, Hwang SI, Han DK, Hla T. A novel method to quantify sphingosine 1-phosphate by immobilized metal affinity chromatography (IMAC). Prostaglandins Other Lipid Mediat. 2007 Nov;84(3-4):154-62. Epub 2007 Aug 6.

101. Subbaramaiah K, Hudis C, Chang SH, Hla T, Dannenberg AJ.EP2 and EP4 receptors regulate aromatase expression in human adipocytes and breast cancer cells. Evidence of a BRCA1 and p300 exchange. J Biol Chem. 2008 8;283(6):3433-44.

102. Wang Z, Liu B, Wang P, Dong X, Fernandez-Hernando C, Li Z, Hla T, Li Z, Claffey K, Smith JD, Wu D. Phospholipase C beta3 deficiency leads to macrophage hypersensitivity to apoptotic induction and reduction of atherosclerosis in mice. J Clin Invest. 2008 118(1):195-204.

103. Sekiguchi M, Iwasaki T, Kitano M, Kuno H, Hashimoto N, Kawahito Y, Azuma M, Hla T, Sano H. Role of Sphingosine 1-Phosphate in the Pathogenesis of Sjogren's Syndrome. J Immunol. 2008 Feb 1;180(3):1921-8.

104. Venkataraman K, Lee YM, Michaud J, Thangada S, Ai Y, Bonkovsky HL, Parikh NS, Habrukowich C, Hla T. Vascular Endothelium As a Contributor of Plasma Sphingosine 1-Phosphate. Circ Res. 2008 Feb 7; 102(6):669-76.

105. Estrada R, Zeng Q, Lu H, Sarojini H, Lee JF, Mathis SP, Sanchez T, Wang E, Kontos CD, Lin CY, Hla T, Haribabu B, Lee MJ. (2008) Up-regulating sphingosine-1-phosphate receptor-2 signaling impairs chemotactic, wound-healing, and morphogenetic responses in senescent endothelial cells. J Biol Chem. 2008 Sep 2.

106. Ghosh M, Ai Y, Narko K, Wang Z, Peters JM, Hla T. PPARdelta is pro-tumorigenic in a mouse model of COX-2-induced mammary cancer. Prostaglandins Other Lipid Mediat. 2008 Dec 24. [Epub ahead of print]

107. Li MH, Sanchez T, Milne GL, Morrow JD, Hla T, Ferrer F. S1P/S1P(2) Signaling Induces Cyclooxygenase-2 Expression in Wilms Tumor. J Urol. 2009 Jan 19. [Epub ahead of print]

108. Li MH, Sanchez T, Yamase H, Hla T, Oo ML, Pappalardo A, Lynch KR, Lin CY, Ferrer F. S1P/S1P(1) signaling stimulates cell migration and invasion in Wilms tumor. Cancer Lett. 2009 Jan 6. [Epub ahead of print]

109. Li MH, Sanchez T, Pappalardo A, Lynch KR, Hla T, Ferrer F. Induction of antiproliferative connective tissue growth factor expression in Wilms' tumor cells by sphingosine-1-phosphate receptor 2. Mol Cancer Res. 2008 Oct;6(10):1649-56.

110. Ter Braak M, Danneberg K, Lichte K, Liphardt K, Ktistakis NT, Pitson SM, Hla T, Jakobs KH, Heringdorf DM. Ga(q)-mediated plasma membrane translocation of sphingosine kinase-1 and cross-activation of S1P receptors. Biochim Biophys Acta. 2009 Feb 2. [Epub ahead of print]

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111. Ghosh M, Aguila HL, Michaud J, Ai Y, Wu M, Hemmes A, Ristimaki A, Guo C, Furneaux H, and Hla T, Essential role of RNA regulator HuR in progenitor cell survival. J. Clin. Invest. 2009 119(12): 3530-3543

112. Michaud J, Im DS, Hla T. Inhibitory role of sphingosine 1-phosphate receptor 2 in macrophage recruitment during inflammation. J Immunol. 2010 Feb 1;184(3):1475-83. Epub 2009 Dec 30. PubMed PMID: 20042570.

113. Thangada S, Khanna KM, Blaho VA, Oo ML, Im DS, Guo C, Lefrancois L, Hla T. Cell-surface residence of sphingosine 1-phosphate receptor 1 on lymphocytes determines lymphocyte egress kinetics. J Exp Med. 2010 Jul 5;207(7):1475-83. Epub 2010 Jun 28. PubMed PMID: 20584883.

114. Habrukowich C, Han DK, Le A, Raizul K, Pan W, Ghosh M, Li Z, Dodge-Kafka K, Jiang X, Bittman R, Hla T. Sphingosine interaction with acidic leucine-rich nuclear phosphoprotein-32A (ANP32A) regulates PP2A activity and cyclooxygenase (COX)-2 expression in human endothelial cells. J Biol Chem. 2010 Jun 17. [Epub ahead of print] PubMed PMID: 20558741.

115. Skoura A, Michaud J, Im DS, Thangada S, Xiong Y, Smith J, Hla T. Sphingosine-1-Phosphate Receptor-2 Function in Myeloid Cells Regulates Vascular Inflammation and Atherosclerosis. Arterioscler Thromb Vasc Biol. 2010 Oct 14.[Epub ahead of print] PubMed PMID: 20947824.

116. Subbaramaiah K, Howe LR, Bhardwaj P, Du B, Gravaghi C, Yantiss RK, Zhou XK, Blaho VA, Hla T, Yang P, Kopelovich L, Hudis CA, Dannenberg AJ. Obesity is associated with inflammation and elevated aromatase expression in the mouse mammary gland. Cancer Prev Res (Phila). 2011 Mar;4(3):329-46. PubMed PMID: 21372033.

117. Oo, ML, Chang, SH, Thangada, S, Wu, MT, Rezaul, MK, Blaho, V, Hwang, SI, Han, DK and Hla, T. (2011) Engagement of S1P1 receptor degradative mechanisms leads to vascular leak in mice. J. Clin. Invest. 2011 Jun 1;121(6):2290-300. doi: 10.1172/JCI45403. Epub 2011 May 9. PubMed PMID: 21555855; PubMed Central PMCID: PMC3104755.

118. Christoffersson, C., Obinata, H., Kumaraswamy, S., Galvani, S., Ahnstrom, J., Sevvana, M., Egerer-Sieber, C., Muller, Y.A., Hla, T., Nielsen, L.B., Dahlback, B. (2011) Endothelium-Protective Sphingosine-1-Phosphate provided by HDL-associated Apolipoprotein M. Proc. Natl. Acad. Sci., USA 2011 Jun 7;108(23):9613-8. Epub 2011 May 23. PubMed PMID: 21606363; PubMed Central PMCID: PMC3111292.

119. Li, Me-Hong, Hla, T., Ferrer, F. (2011) Sphingolipid modulation of angiogenic factor expression in neuroblastoma. Cancer Prev Res (Phila). 2011 Aug;4(8):1325-32. Epub 2011 May 16. PubMed PMID: 21576349; PubMed Central PMCID: PMC3152210.

120. Takeshita H, Kitano M, Iwasaki T, Kitano S, Tsunemi S, Sato C, Sekiguchi M, Azuma N, Miyazawa K, Hla T, Sano H. Sphingosine 1-phosphate (S1P)/S1P receptor 1 signaling regulates receptor activator of NF-κB ligand (RANKL) expression in rheumatoid arthritis. Biochem Biophys Res Commun. 2012 Mar 9;419(2):154-9. doi: 10.1016/j.bbrc.2012.01.103. Epub 2012 Feb 2. PubMed PMID: 22326262.

121. Jung B, Obinata H, Galvani S, Mendelson K, Ding BS, Skoura A, Kinzel B, Brinkmann V, Rafii S, Evans T, Hla T. Flow-Regulated Endothelial S1P Receptor-1 Signaling Sustains Vascular Development. Dev Cell. 2012 Sep 11;23(3):600-10. PubMed PMID: 22975328; PubMed Central PMCID: PMC3443394.

122. Torregroza I, Holtzinger A, Mendelson K, Liu TC, Hla T, Evans T. Regulation of a Vascular Plexus by gata4 Is Mediated in Zebrafish through the Chemokine sdf1a. PLoS One.

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2012;7(10):e46844. doi:1371/journal.pone.0046844. Epub 2012 Oct 3. PubMed PMID: 23056483; PubMed Central PMCID: PMC3463525.

123. Mendelson K, Zygmunt T, Torres-Vazquez J, Evans T, Hla T. Sphingosine-1-Phosphate Receptors S1pr1 and S1pr2 Cooperatively Regulate Embryonic Vascular Development. J Biol Chem. 2012 Dec 10. [Epub ahead of print] PubMed PMID: 23229546.

124. Chang SH, Lu YC, Li X, Hsieh WY, Xiong Y, Ghosh M, Evans T, Elemento O, Hla T. Antagonistic function of the RNA-binding protein HuR and miR-200b in post-transcriptional regulation of VEGF-A expression and angiogenesis. J Biol Chem. 2012 Dec 6. [Epub ahead of print] PubMed PMID: 23223443.

125. Montrose DC, Scherl EJ, Bosworth BP, Zhou XK, Jung B, Dannenberg AJ, Hla T. S1P₁ localizes to the colonic vasculature in ulcerative colitis and maintains blood vessel integrity. J Lipid Res. 2013 Mar;54(3):843-51. doi: 10.1194/jlr.M034108. Epub 2013 Jan 7. PubMed PMID: 23296878.

126. Howe LR, Subbaramaiah K, Kent CV, Zhou XK, Chang SH, Hla T, Jakobsson PJ, Hudis CA, Dannenberg AJ. Genetic deletion of microsomal prostaglandin E synthase-1 suppresses mouse mammary tumor growth and angiogenesis. Prostaglandins Other Lipid Mediat. 2013 Oct;106:99-105. doi:10.1016/j.prostaglandins.2013.04.002. Epub 2013 Apr 25. PubMed PMID: 23624019; PubMed Central PMCID: PMC3830707.

127. Li MH, Hla T, Ferrer F. FTY720 inhibits tumor growth and enhances the tumor-suppressive effect of topotecan in neuroblastoma by interfering with the sphingolipid signaling pathway. Pediatr Blood Cancer. 2013 Sep;60(9):1418-23. doi: 10.1002/pbc.24564. Epub 2013 May 23. PubMed PMID: 23704073; PubMed Central PMCID: PMC3751174.

128. Garris CS, Wu L, Acharya S, Arac A, Blaho VA, Huang Y, Moon BS, Axtell RC, Ho PP, Steinberg GK, Lewis DB, Sobel RA, Han DK, Steinman L, Snyder MP, Hla T, Han MH. Defective sphingosine 1-phosphate receptor 1 (S1P1) phosphorylation exacerbates TH17-mediated autoimmune neuroinflammation. Nature Immunol. 2013 Nov;14(11):1166-72. doi: 10.1038/ni.2730. Epub 2013 Sep 29. PubMed PMID: 24076635.

129. Li X, Lu YC, Dai K, Torregroza I, Hla T, Evans T. Elavl1a regulates zebrafish erythropoiesis via posttranscriptional control of gata1. Blood. 2014 Feb 27;123(9):1384-92. doi: 10.1182/blood-2013-09-526962. Epub 2014 Jan 14. PubMed PMID: 24425803; PubMed Central PMCID: PMC3938149.

130. Thangada S, Shapiro LH, Silva C, Yamase H, Hla T, Ferrer FA. Treatment with the immunomodulator FTY720 (fingolimod) significantly reduces renal inflammation in murine unilateral ureteral obstruction. J Urol. 2014 May;191(5 Suppl):1508-16. doi: 10.1016/j.juro.2013.10.072. Epub 2014 Mar 26. PubMed PMID: 24679864.

131. Murakami K, Kohno M, Kadoya M, Nagahara H, Fujii W, Seno T, Yamamoto A, Oda R, Fujiwara H, Kubo T, Morita S, Nakada H, Hla T, Kawahito Y. Knock out of S1P3 receptor signaling attenuates inflammation and fibrosis in bleomycin-induced lung injury mice model. PLoS One. 2014 Sep 8;9(9):e106792. doi: 10.1371/journal.pone.0106792. eCollection 2014. PubMed PMID: 25198418; PubMed Central PMCID: PMC4157792.

132. Huang C, Gonzalez DG, Cote CM, Jiang Y, Hatzi K, Teater M, Dai K, Hla T, Haberman AM, Melnick A. The BCL6 RD2 domain governs commitment of activated B cells to form germinal centers. Cell Reports 2014 Sep 11;8(5):1497-508. doi: 10.1016/j.celrep.2014.07.059. Epub 2014 Aug 28. PubMed PMID: 25176650; PubMed Central PMCID: PMC4163070.

133. Xiong, Y., Yang, P., Proia, R. and Hla, T. Erythrocyte-derived sphingosine 1-phosphate is

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essential for vascular development.J. Clin. Invest. 2014 Sep 24. pii: 77685. doi: 10.1172/JCI77685. [Epub ahead of print] PubMed PMID: 25250575.

134. Obinata H, Gutkind S, Stitham J, Okuno T, Yokomizo T, Hwa J, Hla T. Individual variation of human sphingosine 1-phosphate receptor 1 coding sequence leads to heterogeneity in receptor function and drug interactions. J Lipid Res. 2014 Oct 7. pii: jlr.P054163. [Epub ahead of print] PubMed PMID: 25293589.

135. Li MH, Harel M, Hla T, Ferrer F. Induction of chemokine (C-C motif) ligand 2 by sphingosine-1-phosphate signaling in neuroblastoma. J Pediatr Surg. 2014 Aug;49(8):1286-91. doi: 10.1016/j.jpedsurg.2014.04.001. Epub 2014 May 16. PubMed PMID: 25092091; PubMed Central PMCID: PMC4122984.

136. Giammanco A, Blanc V, Montenegro G, Klos C, Xie Y, Kennedy S, Luo J, Chang SH, Hla T, Nalbantoglu I, Dharmarajan S, Davidson NO. Intestinal Epithelial HuR Modulates Distinct Pathways of Proliferation and Apoptosis and Attenuates Small Intestinal and Colonic Tumor Development. Cancer Res. 2014 Sep 15;74(18):5322-5335. Epub 2014 Aug 1. PubMed PMID: 25085247; PubMed Central PMCID: PMC4167566.

137. Chang, SH, Elemento, O, Zhang, J, Zhuang, Z, Simons, M and Hla, T (2014) ELAVL1 regulates alternative splicing of eIF4E transporter to promote postnatal angiogenesis. Proc. Natl. Acad. Sci., USA 2014 Dec 23;111(51):18309-14. doi: 10.1073/pnas.1412172111. Epub 2014 Nov 24.

138. Lu, YC, Chang, SH, Hafner, M, Li, X, Tuschl, T, Elemento, O, Hla, T (2014) ELAVL1 modulates transcriptome-wide miRNA binding in murine macrophages. Cell Reports 2014 Dec 24;9(6):2330-43. doi: 10.1016/j.celrep.2014.11.030. Epub 2014 Dec 18.

139. Blaho, VA, Galvani, S, Engelbrecht, E, Liu, CH, Swendeman, SL, Kono, M, Proia, RL, Steinman, L, Han, MH and Hla, T (2015) HDL-bound sphingosine 1-phosphate restrains lymphopoiesis and neuroinflammation. Nature 2015 Jul 16;523(7560):342-6. doi:10.1038/nature14462. Epub 2015 Jun 8. PubMed PMID: 26053123; PubMed Central PMCID: PMC4506268.

140. Mendelson, K.,Lan, Y., Hla, T. and Evans, T. (2015) Maternal or Zygotic Sphingosine Kinase is Required to Regulate Zebrafish Cardiogenesis. Dev Dyn. 2015 Aug;244(8):948-54.doi: 10.1002/dvdy.24288. Epub 2015 Jul 6. PubMed PMID: 25997406; PubMed Central PMCID: PMC4520754.

141. Li, M-H., Swenson, R., Harel, M., Jana, S., Stolarzewicz, E., Hla, T., Shapiro, LH, Ferrer, F. (2015) Antitumor activity of a novel S1P2 antagonist, AB1, in neuroblastoma. J. Pharm. Exp. Ther. 2015 Sep;354(3):261-8. doi:10.1124/jpet.115.224519. Epub 2015 Jun 23. PubMed PMID: 26105954; PubMed Central PMCID: PMC4538871.

142. Galvani, S., Sanson, M., Blaho, V, Swendeman, SL, Conger, H., Dahlback, B, Kono, M., Proia, RL, Smith, JD and Hla, T. (2015) HDL-bound sphingosine 1-phosphate acts as a biased agonist for the endothelial cell receptor S1P1 to limit vascular inflammation Science Signaling 2015 Aug 11;8(389):ra79. doi: 10.1126/scisignal.aaa2581. PubMed PMID: 26268607.

143. Cantalupo A, Zhang Y, Kothiya M, Galvani S, Obinata H, Bucci M, Giordano FJ, Jiang XC, Hla T, Di Lorenzo A. Nogo-B regulates endothelial sphingolipid homeostasis to control vascular function and blood pressure. Nat Med. 2015Sep;21(9):1028-37. doi: 10.1038/nm.3934. Epub 2015 Aug 24. PubMed PMID: 26301690.

144. Etemadi N, Chopin M, Anderton H, Tanzer MC, Rickard JA, Abeysekra W, Hall C, Spall SK, Wang B, Xiong Y, Hla T, Pitson SM, Bonder CS, Wong WW, Ernst M, Smyth GK, Vaux DL, Nutt

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SL, Nachbur U, Silke J. TRAF2 regulates TNF and NF-κB signalling to suppress apoptosis and skin inflammation independently of Sphingosine kinase-1. Elife. 2015 Dec 23;4. pii: e10592. doi:10.7554/eLife.10592. [Epub ahead of print] PubMed PMID: 26701909.

145. Wagschal A, Najafi-Shoushtari SH, Wang L, Goedeke L, Sinha S, deLemos AS, Black JC, Ramírez CM, Li Y, Tewhey R, Hatoum I, Shah N, Lu Y, Kristo F, Psychogios N, Vrbanac V, Lu YC, Hla T, de Cabo R, Tsang JS, Schadt E, Sabeti PC, Kathiresan S, Cohen DE, Whetstine J, Chung RT, Fernández-Hernando C, Kaplan LM, Bernards A, Gerszten RE, Näär AM. Genome-wide identification of microRNAs regulating cholesterol and triglyceride homeostasis. Nat Med. 2015 Nov;21(11):1290-7. doi: 10.1038/nm.3980. Epub 2015 Oct 26. PubMed PMID: 26501192

146. Christensen PM, Liu CH, Swendeman SL, Obinata H, Qvortrup K, Nielsen LB, Hla T, Di Lorenzo A, Christoffersen C. Impaired endothelial barrier function in apolipoprotein M-deficient mice is dependent on sphingosine-1-phosphate receptor 1. FASEB J. 2016 Mar 8. pii: fj.201500064. [Epub ahead of print] PubMed PMID:26956418.

147. Xiong Y, Lee HJ, Mariko B, Lu YC, Dannenberg AJ, Haka AS, Maxfield FR, Camerer E, Proia RL, Hla T. Sphingosine kinases are not required for inflammatory responses in macrophages. J Biol Chem. 2016 May 20;291(21):11465. doi: 10.1074/jbc.A113.483750. PubMed PMID: 27226645; PubMed Central PMCID: PMC4900292.

148. Gazit SL, Mariko B, Thérond P, Decouture B, Xiong Y, Couty L, Bonnin P, Baudrie V, Le Gall SM, Dizier B, Zoghdani N, Ransinan J, Hamilton JR, Gaussem P, Tharaux PL, Chun J, Coughlin SR, Bachelot-Loza C, Hla T, Ho-Tin-Noé B, Camerer E. Platelet and Erythrocyte Sources of S1P Are Redundant for Vascular Development and Homeostasis, but Both Rendered Essential After Plasma S1P Depletion in Anaphylactic Shock. Circ Res. 2016 Sep 30;119(8):e110-26. doi: 10.1161/CIRCRESAHA.116.308929. PubMed PMID: 27582371; PubMed Central PMCID: PMC5064286.

149. Ding BS, Liu CH, Sun Y, Chen Y, Swendeman SL, Jung B, Chavez D, Cao Z, Christoffersen C, Nielsen LB, Schwab SR, Rafii S, Hla T. HDL activation of endothelial sphingosine-1-phosphate receptor-1 (S1P(1)) promotes regeneration and suppresses fibrosis in the liver. JCI Insight. 2016 Dec 22;1(21):e87058. doi: 10.1172/jci.insight.87058. PubMed PMID: 28018969; PubMed Central PMCID: PMC5161208.

150. Yanagida K, Liu CH, Faraco G, Galvani S, Smith HK, Burg N, Anrather J, Sanchez T, Iadecola C, Hla T. Size-selective opening of the blood-brain barrier by targeting endothelial sphingosine 1-phosphate receptor 1. Proc Natl Acad Sci U S A. 2017 Apr 25;114(17):4531-4536. doi: 10.1073/pnas.1618659114. Epub 2017 Apr 10. PubMed PMID: 28396408; PubMed Central PMCID: PMC5410849.

151. Mendoza A, Fang V, Chen C, Serasinghe M, Verma A, Muller J, Chaluvadi VS, Dustin ML, Hla T, Elemento O, Chipuk JE, Schwab SR. Lymphatic endothelial S1P promotes mitochondrial function and survival in naive T cells. Nature. 2017 Jun 1;546(7656):158-161. doi: 10.1038/nature22352. Epub 2017 May 24. PubMed PMID: 28538737.

152. Cantalupo A, Gargiulo A, Dautaj E, Liu C, Zhang Y, Hla T, Di Lorenzo A. S1PR1 (Sphingosine-1-Phosphate Receptor 1) Signaling Regulates Blood Flow and Pressure. Hypertension. 2017 Aug;70(2):426-434. doi: 10.1161/HYPERTENSIONAHA.117.09088. Epub 2017 Jun 12. PubMed PMID: 28607130; PubMed Central PMCID: PMC5531041.

153. Swendeman SL, Xiong Y, Cantalupo A, Yuan H, Burg N, Hisano Y, Cartier A, Liu CH, Engelbrecht E, Blaho V, Zhang Y, Yanagida K, Galvani S, Obinata H, Salmon JE, Sanchez T, Di

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Lorenzo A, Hla T. An engineered S1P chaperone attenuates hypertension and ischemic injury. Sci Signal. 2017 Aug 15;10(492). pii: eaal2722. doi: 10.1126/scisignal.aal2722. PubMed PMID: 28811382.

154. Singh RK, Haka AS, Brumfield A, Grosheva I, Bhardwaj P, Chin HF, Xiong Y, Hla T, Maxfield FR. Ceramide Activation of RhoA/Rho Kinase Impairs Actin Polymerization during Aggregated LDL Catabolism. J Lipid Res. 2017 Aug 16. pii: jlr.M076398. doi: 10.1194/jlr.M076398. [Epub ahead of print] PubMed PMID: 28814641.

155. Mendelson K, Pandey S, Hisano Y, Carellini F, Das B, Hla T, Evans T. The ceramide synthase 2b gene mediates genomic sensing and regulation of sphingosine levels during zebrafish embryogenesis. Elife. 2017 Sep 28;6. pii: e21992. doi: 10.7554/eLife.21992. [Epub ahead of print] PubMed PMID: 28956531.

156. Kono M, Conlon EG, Lux SY, Yanagida K, Hla T, Proia RL. Bioluminescence imaging of G protein-coupled receptor activation in living mice. Nat Commun. 2017Oct 27;8(1):1163. doi: 10.1038/s41467-017-01340-7. PubMed PMID: 29079828.

157. Ghosh M, Thangada S, Dasgupta O, Khanna KM, Yamase HT, Kashgarian M, Hla T, Shapiro LH, Ferrer FA. Cell-intrinsic sphingosine kinase 2 promotes macrophage polarization and renal inflammation in response to unilateral ureteral obstruction. PLoS One. 2018 Mar 8;13(3):e0194053. doi:10.1371/journal.pone.0194053. eCollection 2018. PubMed PMID: 29518138; PubMedCentral PMCID: PMC5843290.

158. Montrose DC, Zhou XK, McNally EM, Sue E, Wang H, Nishiguchi R, Verma A,Elemento O, Simpson KW, Yang P, Hla T, Dannenberg AJ. Colonoscopic-Guided PinchBiopsies in Mice as a Useful Model for Evaluating the Roles of Host and LuminalFactors in Colonic Inflammation. Am J Pathol. 2018 Dec;188(12):2811-2825. doi:10.1016/j.ajpath.2018.08.016. Epub 2018 Sep 28. PubMed PMID: 30273600; PubMedCentral PMCID: PMC6334259.

159. Burg N, Swendeman S, Worgall S, Hla T, Salmon JE. Sphingosine 1-Phosphate Receptor 1 Signaling Maintains Endothelial Cell Barrier Function and Protects Against Immune Complex-Induced Vascular Injury. Arthritis Rheumatol. 2018 Nov;70(11):1879-1889. doi: 10.1002/art.40558. PubMed PMID: 29781582.

Other peer-reviewed publications:

1. Hla, T. (1999) Molecules in focus: Cox-1 and Cox-2 isoenzymes. Int. J. Of Biochem. Cell Biol. 31, 551-557.

2. Hla, T., Lee, M., Ancellin, N., Liu, C.H., Thangada, S., Thompson, B.D. and Kluk, M. (1999) Sphingosine-1-phosphate: Extrcellular mediator or intracellular second messenger ? Biochem. Pharm. 58(2) 201-207.

3. Bishop-Bailey D, Hla T, Mitchell JA (1999) Cyclooxygenase-2 in vascular smooth muscle. Int J Mol Med 1:41-48

4. Kluk, M. and Hla, T. (2002) Signaling of sphingosine-1-phosphate via the S1P/EDG-family of G-protein-coupled receptors. Biochim. Biophys. Acta 1582(1-3):72-80.

5. Bishop-Bailey D, Calatayud S, Warner TD, Hla T, Mitchell JA. (2002) Prostaglandins and the regulation of tumor growth. J Environ Pathol Toxicol Oncol. 21(2):93-101.

6. Hla, T., Lee, M.-J., Ancellin, N., Paik, J. H., Kluk, M.J. (2001) Lysophospholipids – receptor

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revelations. Science 294, 1875-1878. 7. Hla, T. (2001) Sphingosine 1-phosphate Receptors. Prostaglandins and Lipid Mediators. 64,

135-142. 8. Hla, T. (2003) Signaling and biological actions of sphingosine 1-phosphate. Pharm. Res. 47, 5,

401-407. 9. Ozaki H, Hla T, Lee MJ. (2003) Sphingosine-1-phosphate signaling in endothelial activation. J

Atheroscler Thromb. 2003;10(3):125-31. 10. Trifan OC, Hla T. (2003) Cyclooxygenase-2 modulates cellular growth and promotes

tumorigenesis. J Cell Mol Med. 2003 Jul-Sep;7(3):207-22. 11. Saba, JD and Hla, T. (2004) Point-counterpoint of sphingosine 1-phosphate metabolism. Circ.

Res. 94: 724 – 734 12. Brinkmann, V, Cyster, JG, Hla, T. (2004) FTY720: Sphingosine 1-Phosphate Receptor-1 in the

Control of Lymphocyte Egress and Endothelial Barrier Function. Am J Transplant. 4(7):1019-25 13. Sanchez T, Hla T. (2004) Structural and functional characteristics of S1P receptors. J Cell

Biochem. 92(5): 913-22. 14. Simmons DL, Botting RM, Hla T. (2004) Cyclooxygenase isozymes: the biology of prostaglandin

synthesis and inhibition. Pharmacol Rev. 2004 Sep; 56(3):387-437. 15. Chae SS, Hla T. (2005) Inhibition of gene expression in vivo using multiplex siRNA. Methods

Mol Biol. 2005;309:197-203. 16. Hla T. (2005) Dietary factors and immunological consequences. Science. Sep 9;309(5741):1682-

3. 17. Hla T. (2005) Genomic insights into mediator lipidomics. Prostaglandins Other Lipid Mediat.

2005 Sep;77(1-4):197-209. 18. Rapaka RS, Hla T, Dey SK. (2005) The dawn of lipidomics. Prostaglandins Other Lipid

Mediat. 2005 Sep;77(1-4):1-3. 19. Hla, T., Venkataraman, K, Micahud, J (2008) The vascular S1P gradient – cellular sources and

biological significance. Biochim. Biophys. Acta 1781(9):477-82 20. Skoura A, Hla T. Lysophospholipid receptors in vertebrate development, physiology and

pathology. J Lipid Res. 2008 Dec 8. [Epub ahead of print] 21. Skoura A, Hla T. Regulation of vascular physiology and pathology by the S1P2 receptor subtype

Cardiovasc Res. 2009 Mar 15. [Epub ahead of print] 22. Hla T, Im DS. The ABCs of lipophile transport. Science. 2009 Feb 13;323(5916):883-4. 23. Hla, T. Plugging vascular leak by sphingosine kinase from bone marrow progenitor cells. Circ

Res. 2009; 105;614-616. 24. Hla T, Oo ML. Ramping up RANTES in the acute response to arterial injury. J Clin Invest. 2010

Jan;120(1):90-2. doi: 10.1172/JCI41738. Epub 2009 Dec 28. PubMed PMID: 20038805; PubMed Central PMCID: PMC2798704.

25. Chun J, Hla T, Lynch KR, Spiegel S, Moolenaar WH. International Union of Basic and Clinical Pharmacology. LXXVIII. Lysophospholipid Receptor Nomenclature. Pharmacol Rev. 2010

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Dec;62(4):579-87. PubMed PMID: 21079037. 26. Hla T, Brinkmann V. Sphingosine 1-phosphate (S1P): Physiology and the effects of S1P receptor

modulation. Neurology. 2011 Feb 22;76(8 Suppl 3):S3-8. Review. PubMed PMID: 21339489. 27. Obinata H, Hla T. Sphingosine 1-phosphate in coagulation and inflammation. Semin

Immunopathol. 2011 Jul 31. [Epub ahead of print] PubMed PMID: 21805322. 28. Chang SH, Hla T. Gene regulation by RNA binding proteins and microRNAs in angiogenesis.

Trends Mol Med. 2011 Jul 29. [Epub ahead of print] PubMed PMID: 21802991. 29. Blaho VA, Hla T. Regulation of mammalian physiology, development, and disease by the

sphingosine 1-phosphate and lysophosphatidic acid receptors. Chem Rev.2011 12;111(10):6299-320. Epub 2011 Sep 22. PubMed PMID: 21939239; PubMed Central PMCID: PMC3216694.

30. Moolenaar WH, Hla T. SnapShot: Bioactive Lysophospholipids. Cell. 2012 Jan 20;148(1-2):378-378.e2. PubMed PMID: 22265422.

31. Obinata H, Hla T. Fine-Tuning S1P Therapeutics. Chem Biol. 2012 Sep 21;19(9):1080-2. doi: 10.1016/j.chembiol.2012.09.002. PubMed PMID: 22999874.

32. Hla T, Dannenberg AJ. Sphingolipid signaling in metabolic disorders. Cell Metab. 2012 Oct 3;16(4):420-34. doi: 10.1016/j.cmet.2012.06.017. Epub 2012 Sep 13. PubMed PMID: 22982021; PubMed Central PMCID: PMC3466368.

33. Hla T, Galvani S, Rafii S, Nachman R. S1P and the birth of platelets. J Exp Med. 2012 Nov 19;209(12):2137-40. doi: 10.1084/jem.20122284. PubMed PMID: 23166370; PubMed Central PMCID: PMC3501358.

34. Mendelson, K., Evans, T. and Hla, T. (2014) Sphingosine 1-phosphate signaling. Development 141(1), 5-9. doi: 10.1242/dev.094805. PMID: 24346695

35. Blaho VA, Hla T. An update on the biology of sphingosine 1-phosphate receptors. J Lipid Res. 2014 Jan 23. [Epub ahead of print] PubMed PMID: 24459205.

36. Garris CS, Blaho VA, Hla T, Han MH. Sphingosine-1-phosphate Receptor 1 (S1P(1)) Signaling in T cells: Trafficking and Beyond. Immunology. 2014 Mar 5. doi:10.1111/imm.12272. [Epub ahead of print] PubMed PMID: 24597601.

37. Chang SH, Hla T. Post-transcriptional gene regulation by HuR and microRNAs in angiogenesis. Curr Opin Hematol. 2014 May;21(3):235-40. Doi 10.1097/MOH.0000000000000040. PubMed PMID: 24714527.

38. Xiong Y, Hla T. S1P Control of Endothelial Integrity. Curr Top Microbiol Immunol. 2014;378:85-105. doi: 10.1007/978-3-319-05879-5_4. PubMed PMID: 24728594.

39. Camm, J, Hla, T, Bakshi, R, Brinkmann, V., Cardiac and vascular effects of fingolimod: Mechanistic basis and clinical implications. Am Heart J. 2014 Nov;168(5):632-644. doi: 10.1016/j.ahj.2014.06.028. Epub 2014 Jul 11.

40. Hla, T and Kolesnick, R. C16:0-ceramide signals insulin resistance. Cell Metabolism 2014 Nov 4;20(5):703-5. doi: 10.1016/j.cmet.2014.10.017. Epub 2014 Nov 4.

41. Proia, RL and Hla, T., Emerging biology of sphingosine-1-phosphate: Role in pathogenesis and therapy. J. Clin. Invest. 2015 125(4): 1379-1387.

42. Yanagida K, Hla T. Vascular and Immunobiology of the Circulatory Sphingosine 1-Phosphate

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Gradient. Annu Rev Physiol. 2016 Oct 21. [Epub ahead of print] PubMed PMID: 27813829 43. Hisano Y, Hla T. Bioactive lysolipids in cancer and angiogenesis. Pharmacol Ther. 2019

Jan;193:91-98. doi: 10.1016/j.pharmthera.2018.07.006. Epub 2018 Jul 23. Review. PubMed PMID: 30048709; PubMed Central PMCID: PMC6309747.

Reviews, chapters, monographs and editorials: 1. Hla, T.(1994) Early Response Genes in Endothelial Cells. IN: Angiogenesis: Molecular Biology

and Clinical Applications. ed. Maragoudakis, M.E., Plenum Press, New York. pp. 67-72. 2. Hla, T., Ristimäki, A., Appleby, S. and Barriocanal, J. (1993) Cyclooxygenase Gene Expression

in Angiogenesis and Chronic Inflammatory Disease. Ann. New York Acad. Sci. 696, 197-204. 3. Smith, W.L., DeWitt, D.L., Kraemer, S.A., Andrews, M.J., Hla, T., Maciag, T. and Shimokawa,

T. (1990) Structure-Function Relationships in Sheep, Mouse and Human Prostaglandin Endoperoxide G/H Synthases. Adv. Pros. Thromb. Leuk. Res. 20:14-21.

4. Bailey, J.M., Muza, B., Hla, T. and Pash, J. (1985) The role of epidermal growth factor in cyclooxygenase synthesis. IN: Prostaglandins and Leukotrienes XVII, eds., Hayaishi and Yamamoto, Raven Press, New York pp.141-142.

5. Bailey, J.M., Hla, T., Muza, B. and Pash, J. (1985) Regulation of cyclooxygenase synthesis in vascular smooth muscle cells by epidermal growth factor. IN: Prostaglandins, Leukotrienes and Lipoxins, eds., J.M. Bailey, Plenum Press, New York, pp.147-156.

6. Hla, T.(1991) Regulation of Cyclooxygenase Gene Expression in Vascular Endothelial Cells. IN: Prostaglandins, Leukotrienes, Lipoxins and PAF, ed. Bailey, J.M., Plenum Press, New York, pp. 53-58.

7. Hla, T., Ristimaki, A., Ben-Av., P., Narko, K., Lee, M., Evans, M., Liu, C. And Sano, H. (1996) Role of Cox-2 Pathway in Angiogenic Diseases. IN: Angiogenesis: Basic Aspects and Clinical Applications. ed. Maragoudakis, M.E., Plenum Press, New York. pp. 191-198.

8. Narko, K., Ristimaki, A., Ben-Av, P. And Hla, T. (1996) Regulation of expression and functional role of Cyclooxygenase-2. IN: Frontiers in Bioactive Lipids. ed. Vanderhoek, JY., Plenum Press, New York, pp. 105-109.

9. Sano, H, Hashiramoto, A, Kawahito, Y, Yamada, R, Nakajima, H, Hla, T. and Kondo, M (1998) Antisense therapy for Rheumatoid Arthritis. IN: Molecular and Genetic Approaches to Diseases - Immunology, Hematology, Oncology - ed: Niho, N., Kyushu University Press, Japan. pp 123-140.

10. Lee, M-J, Thangada, S, Liu, CH, Ancellin, N, Thompson, BD, Kluk, M and Hla, T. (1999) EDG-1: an endothelial cell-derived bioactive lipid receptor. Angiogenesis in Health and Disease. Editor: Gabor Rubanyi, Marcel Dekker, NY. pp 125-131.

11. Hla, T., Lee, M-J., Ancellin, N., Thangada, S., Liu, C.H., Kluk,M., Chae, S.-S., and Wu, M.-T. (2000) Sphingosine-1-phosphate signaling via the EDG-1 family of G-protein-coupled receptors. Ann NY Acad Sci. 905: 16-24.

12. Ancellin, N. and Hla, T. (2000) Switching intracellular signaling pathways to study sphingosine-1-phosphate receptors. Ann NY Acad Sci. 905: 260-262.

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13. Hla T. (2004) Physiological and pathological actions of sphingosine 1-phosphate. Semin Cell Dev Biol. 15(5): 513-20.

14. Chae, SS, Paik, JH, Shubert-Coleman, J, Furneaux, H and Hla, T. (2004) Application of RNA interference (RNAi) technology to angiogenesis research. Methods in Endothelial Cell Biology. (Augustin, H ed.) Springer-Verlag, Berlin, pp. 167-176.

15. Obinata H, Hla T. Assessment of sphingosine-1-phosphate activity in biological samples by receptor internalization and adherens junction formation. Methods Mol Biol. 2012;874:69-76. doi: 10.1007/978-1-61779-800-9_6. PubMed PMID: 22528440.

16. Galvani S, Hla T. Quality Versus Quantity: Making HDL Great Again. Arterioscler Thromb Vasc Biol. 2017 Jun;37(6):1018-1019. doi: 10.1161/ATVBAHA.117.309441. PubMed PMID: 28539490; PubMed Central PMCID: PMC5498076.

17. Yanagida K, Hla T. A dark side to omega-3 fatty acids. Nature. 2017 Dec 14;552(7684):180-181. doi: 10.1038/d41586-017-07678-8. PubMed PMID: 29239390.

Thesis Molecular approaches to the study of prostacyclin synthesis and its regulation in vascular cells by Hla, Timothy Tun, The George Washington University, 1988, 246 pages; 8815955 Current Research Interests Lipid mediator networks Biology of sphingolipids Role of sphingosine 1-phosphate (S1P) in biology and disease Development of novel therapeutics based on S1P signaling Gene expression mechanisms in vascular biology and disease

Narrative Report

My laboratory discovered and cloned two molecules involved in bioactive lipid signaling and increased our understanding of how such mechanisms contribute to physiology and diseases. I am very proud of the fact that both molecules are targets of two FDA-approved drugs as detailed below.

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My early years of training in graduate school were greatly influenced by the work of the late vascular biologist Judah Folkman, a pioneer who described and popularized angiogenesis. I decided to focus my postdoctoral work on cloning and identification of molecules in endothelial cells that regulate angiogenesis, with the hope that these molecules would turn out to be novel therapeutic targets in chronic diseases such as cancer and inflammatory conditions.

My laboratory cloned and “deorphaned” the first sphingosine 1-phosphate (S1P) receptor, thus discovering that this molecule acts as an extracellular bioactive lipid mediator. We cloned the inducible endothelial G protein-coupled receptor (GPCR), EDG-1 as an early response gene from human endothelial cells in 1990 (J. Biol. Chem., 265:9308-9313). Although the identification of the ligand for this receptor was challenging, we persevered and provided unequivocal proof in 1998 that EDG-1 is the high affinity receptor for sphingosine 1-phosphate (S1P) (Science 279, 1552-1556). At the time it was not well accepted that S1P has cell surface receptors. In fact there was great skepticism that lysophopholipids such as S1P were bona fide extracellular lipid mediators. There was also an alternate notion that S1P acted intracellularly as a second messenger. Our paper helped change the prevailing concepts about lysophospholipid signaling and also described the surprising finding that G protein-coupled receptors regulated cellular adherens junctions. This novel concept was further explored in a publication in 1999 that specific S1P receptor subtypes regulated small GTPases Rho and Rac to modulate adherens junction assembly and morphogenesis of endothelial cells into capillary-like tubules (Cell 99 (3), 301-312). In addition, S1P cooperated with polypeptide angiogenic factors (VEGF and FGF) to induce mature vessels in vivo. These early studies, together with the demonstration of embryonic lethality of the S1P receptor knockout mice by the Proia lab, helped establish the early concept that this GPCR mediates key vascular signaling events. S1P is now recognized as a vital signaling molecule in vascular development, homeostasis and disease.

This discovery of S1P receptor served as a solid foundation in the launch of immune modulatory S1P receptor drugs, exemplified by Fingolimod/ Gilenya. The findings by Merck and Novartis scientists that Fingolimod, a derivative of a fungal metabolite originally discovered by Chiba and collagues in Japan, is a sphingosine analog that gets phosphorylated to act on S1P receptors not only accelerated the development of this compound as an immunomodulator, but also opened up a new field in immunology regarding the mechanisms of lymphocyte egress. Our laboratory showed that Fingolimod is phosphorylated by sphingosine kinase-2 (J. Biol. Chem 278, 47281-47290). Our work also helped define the mechanisms by which S1P receptor on immune cells regulate lymphocyte egress (J Exp Med. 207(7):1475-83) and factors that determine efficacy and adverse events of S1P receptor modulators (J. Clin. Invest. 121(6):2290-300). Therefore, our studies defined physiological actions of sphingosine 1-phosphate and contributed to the development of the S1P receptor-targeted drug (Fingolimod/Gilenya), the first oral medication for multiple sclerosis which is approved in > 40 countries.

Recently we discovered that S1P is “chaperoned” by apolipoprotein M in the high density lipoprotein (HDL) particles, which are known to protect from cardiovascular disease. We proposed the concept that chaperones modulate the biological activity of lipid mediators by promoting “biased” signaling on receptors. This conceptual advance is stimulating current efforts to find novel pharmacological tools in the treatment of vascular and immune diseases. Indeed, we recently reported that ApoM-Fc, an engineered S1P chaperone alleviated ischemia reperfusion injury in preclinical models and could serve as a novel therapeutic in stroke and myocardial infarction.This is a major area of research in my laboratory currently. We are attempting to understand how HDL-S1P signaling occurs at the cell membrane, immunological and vascular consequences of HDL-S1P signaling and development of novel therapeutics

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that mimic HDL-S1P.

We also contributed to another lipid mediator signaling system, i.e. the prostaglandins. As a graduate student, my work focused on regulation of expression of the cyclooxygenase (COX), a rate-limiting enzyme in the biosynthesis of prostaglandins. Contrary to the prevailing view at the time, our results suggested that the COX enzyme is induced by growth factors in vascular cells, suggesting that this might constitute a pathophysiologic mechanism in inflammation. During and shortly after my postdoctoral years, we cloned the human COX-2 cDNA and published the findings in 1992. This was a major finding because in addition to the cDNA sequence, our paper described the sensitivity of COX-2 enzymatic activity by non-steroidal anti-inflammatory drugs (Proc. Natl. Acad. Sci., USA. 89:7384-7388). We also described the regulation of this gene in vascular and inflammatory cells, and showed that COX-2 is upregulated in many human diseases, including rheumatoid arthritis (J. Clin. Invest. 93, 1095-1101) and cancer (Cancer Res. 55, 3785-3789). In addition, we demonstrated that transgenic overexpression of COX-2 leads to tumor formation accompanied by abnormal angiogenesis. Our work served as a basis for the development of COX-2-selective inhibitors (Coxibs) by the pharmaceutical industry (e.g. Celebrex) to inhibit inflammation and suggested that COX-2 inhibitors may be useful in treating some cancers. Even though recent epidemiological data show that COX-2 inhibitors pose a significant cardiovascular risk, mechanisms remain poorly understood and evidence-based risk stratification is not available. We have contributed to this area in a recent publication (J Exp Med. 204(9):2053-61). Recently, my laboratory has been working on cross talk between S1P and prostanoid signaling systems in the vascular system. In the area of education, I have given didactic lectures to MD students and graduate students pursuing the PhD degree. In the first case, I was involved in the design and teaching of the vascular biology curriculum for first year MD students at the UConn School of Medicine. At Weill Cornell, I contributed to teaching biochemistry of lipids, lipid signaling and cell signaling via G proteins for first year MD students. For PhD students, I have taught several lectures on lipid biology, lipid biochemistry, vascular biology and G protein-coupled signal transduction at both institutions. In addition, I have been involved in research training of pre- and post-doctoral scientists throughout my career. Administratively, I have recruited and mentored several tenure track faculty at both UConn and Cornell as Director of the Vascular Biology Center. In addition, I have been involved in administering group grants such as the NIH PO1s and the Leducq transatlantic network grant. I wrote, renewed and ran a NHLBI PPG at UConn from 2002-2014. My laboratory at the Vascular Biology Program at Boston Children’s Hospital (https://projects.iq.harvard.edu/hlalab) is staffed by 12 scientists who are actively working on projects to understand the fundamental mechanisms of bioactive lipid signaling in vascular biology and disease.