CURRICULUM VITAE1990 John J. Sampson Research Award, AHA California Affiliate (highest score for Grant-in-Aid) 1991 Established Investigator Award, American Heart Association 1991

Prepared: November 29, 2018

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CURRICULUM VITAE

Name: Shaun R Coughlin, MD, PhD Position: Global Head, Cardiovascular and Metabolic Diseases

Novartis Institutes of Biomedical Research Professor Emeritus, Step A/S

Cardiovascular Research Institute, Department of Medicine, Department of Cellular and Molecular Pharmacology

University of California, San Francisco Address: Novartis Institutes of Biomedical Research

22 Windsor Street 4D-320A Cambridge, MA 02141

Email: [email protected]

EDUCATION 1972 - 1976 Massachusetts Institute of

Technology S.B. Biology

1972 - 1976 Massachusetts Institute of Technology

S.B. Physics


S.M. Biochemistry and Metabolism


Ph.D. Neural and Endocrine Regulation

M. Moskowitz

1976 - 1982 Harvard Medical School (Harvard-M.I.T. Division of Health Sciences and Technology)

M.D.

1982 - 1984 Massachusetts General Hopsital Residency Internal Medicine

1984 - 1986 University of California, San Francisco

Cardiology Fellow and Postdoctoral Fellow

L.T. Williams

LICENSES, CERTIFICATION 1986 Diplomat, Internal Medicine

1982 Massachusetts

1984 California


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PRINCIPAL POSITIONS HELD 1985 - 1986 Howard Hughes Medical Institute Associate

1986 - 1991 University of California, San Francisco Assistant Professor In Residence

Medicine (Cardiology)

1986 - 1990 Howard Hughes Medical Institute Assistant Investigator

1986 - 1991 University of California, San Francisco Associate Staff Cardiovascular Research Institute

1991 - present University of California, San Francisco Senior Staff Cardiovascular Research Institute

1991 - 1992 University of California, San Francisco Associate Professor In Residence


1992 - 1996 University of California, San Francisco Associate Professor Ladder Rank


1992 - 1996 University of California, San Francisco Associate Director Cardiovascular Research Institute

1996 - 2017 University of California, San Francisco Professor Ladder Rank


1997 - 2017 University of California, San Francisco Professor (joint appointment)

Molecular and Cellular Pharmacology

1997 - 2017 University of California, San Francisco Director Cardiovascular Research Institute

2006 - 2017 University of California, San Francisco Distinguished Professor of Cardiovascular Biology and Medicine

Cardiovascular Research Institute

2017 - present Novartis Global Head Cardiovascular and Metabolism


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OTHER POSITIONS HELD CONCURRENTLY 1991 - 2017 University of California, San Francisco Member Molecular

Medicine Program (postgrad training program)

1992 - 2017 University of California, San Francisco Member Biomedical Sciences Program (predoctoral training)

1992 - 2017 University of California, San Francisco Member Program in Biological Sciences (predoctoral training)

1995 - 2001 University of California, San Francisco Director Daiichi Research Center

HONORS AND AWARDS 1972 National Merit Scholar

1975 Phi Beta Kappa, M.I.T.

1976 Sigma Xi, M.I.T.

1976 Harvard National Scholar, Harvard Medical School

1978 Medical Scientist Training Program Fellow, Harvard Medical School

1979 Insurance Medical Scientist Scholar, Insurance Medical Scientist Scholarship Fund, Springfield, MA

1982 Leon Resnick Award for Excellence and Accomplishment in Research, Harvard Medical School

1982 American Heart Association Stroke Research Fellowship

1982 M.D. Magna Cum Laude, Harvard Medical School


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1990 John J. Sampson Research Award, AHA California Affiliate (highest score for Grant-in-Aid)

1991 Established Investigator Award, American Heart Association

1991 ASCI Plenary Session Presentation

1991 AFCR Henry Christian Award

1991 Young Investigator Award, WSCI

1992 American Society for Clinical Investigation.

1994 Syntex Prize in Receptor Pharmacology.

1995 Western Association of Physicians

1997 American Association of Physicians

1998 Outstanding Investigator Award, American Federation of Medical Research

2000 Hoeg Award, American Heart Association

2001 Beyer Visiting Professor, University of Wisconsin MSTP Program

2002 Belfer Visiting Professor, Johns Hopkins School of Medicine

2002 Elected to American Academy of Arts and Sciences

2003 Pasarow Foundation Award for Cardiovascular Research

2003 Basic Science Prize, American Heart Association

2004 Borun Visiting Professor, UCLA

2004 14th Annual Bristol-Myers Squibb Award for Distinguished Achievement in Cardiovascular Research

2004 Elected to National Academy of Sciences

2004 Elected to Institute of Medicine of the National Academies (now National Academy of Medicine)

2005 48th Annual Faculty Research Lecture, UCSF


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2006 Bristol-Myers Squibb Freedom to Discover Unrestricted Grant

2006 Stanley Korsmeyer ASCI Award

2007 Distinguished Scientist of the American Heart Association

2008 Earl Benditt Award, ASIP/NAVBO

2009 Wu Visiting Professor, Columbia

2010 Keystone GPCR Meeting, Keynote Lecture

2011 Metcalfe Lecture, OHSU

2011 Bristow Lecture, University of Illinois, Chicago

2011 Distinguished Career Award, International Society on Thrombosis and Haemostasis

2011 Louis and Arthur Lucian Award, McGill University

2012 Distinguished Scientist Lecture, American Heart Association

2014 Research Achievement Award, American Heart Association

2015 UCSF 150th Anniversary Alumni Excellence Award

KEYWORDS/AREAS OF INTEREST molecular biology, cell biology, cardiovascular biology, hemostasis and thrombosis, proteases, protease-activated receptors, G protein-coupled receptors, signaling mechanisms, therapeutic development

PROFESSIONAL ACTIVITIES MEMBERSHIPS 1975 - Phi Beta Kappa

1976 - Sigma Xi

1986 - American Federation for Clinical Research

1989 - American Heart Association Council on Basic Science

1992 - American Society for Clinical Investigation

1992 - American Society for Investigative Pathology

1994 - North American Vascular Biology Organization


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1995 - Western Association of Physicians

1997 - American Association of Physicians

1998 - Association of University Cardiologists

2002 - American Academy of Arts and Sciences

2004 - National Academy of Sciences

2004 - Institute of Medicine of the National Academies

SERVICE TO PROFESSIONAL PUBLICATIONS 1992 - 2000 Editorial Board, Trends in Cardiovascular Medicine

1994 - 2000 Editorial Board, Molecular Medicine

1998 - 2008 Editorial Board, Journal of Clinical Investigation

2012 - present Editorial Board, Journal of Clinical Investigation

- Ad hoc for multiple journals (Science, Nature, Cell, Dev. Cell, Nature Medicine, PNAS, etc.)

INVITED PRESENTATIONS - INTERNATIONAL 1992 Third Biennial Meeting on Blood Coagulation and Platelet

Biology

1992 Senri International Symposium on Atherosclerosis

1992 International Society for Applied Cardiovascular Biology

1992 International Symposium on the Biology of Vascular Cells

1992 Ares-Serono Symposium on G protein-coupled receptors, Geneva

1993 XIVth International Congress on Thrombosis and Haemostasis

1993 European Biochemical Society Meeting, Vienna

1995 International Symposium on Endothelium

1995 Alfred Benzon Symposium on G Protein-Coupled Receptors, Copenhagen

1995 Keynote speaker, IXth annual Vessel Research Conference, Tokyo

1996 Keynote Speaker, Japanese Society for Haemostasis and Thrombosis, Yamanashi, Japan

1996 International Society of Haematology, Singapore

1996 International Conference on Cell Biology, Symposium talk


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1997 Keynote Speaker, 117th Japanese Pharmacology Association Meeting

1997 International Congress of Biochemistry and Molecular Biology, Symposium talk

1997 Owren Memorial Lecture, Oslo, Norway

1999 International Society for Thrombosis and Hemostasis Protease Symposium

2001 State of the Art Lecture, International Society for Thrombosis and Haemostasis Congress, Paris

2002 NL Congressi Annual Meeting on Thrombosis, La Thuile

2002 Molecular Medicine 2002, Reykjavik

2003 Symposium Lecture, International Society for Thrombosis and Haemostasis Congress, Birmingham, UK

2004 Sixth International Winter Meeting on Coagulation - La Thuile

2005 Symposium Lecture, International Society for Thrombosis and Haemostasis Congress, Sydney, Australia

2006 Seventh International Winter Meeting on Coagulation - La Thuile

2007 International Society of Thrombosis and Haemostasis, Symposium talk, Geneva

2009 European Vascular Biology Organization Annual Meeting, Marseilles

2010 Mikamo Lecture, Japanese Cardiology Society annual meeting, Kyoto

2010 Keystone Meeting on Bioactive Lipids, Kyoto

2012 International Vascular Biology Meeting, Weisbaden

2012 Lucian Award Lecture, McGill

2013 International Society for Heart Research Congress

2014 Atherosclerosis, Thrombosis, and Vascular Biology Meeting, Toronto

2014 Merck Global Therapeutic Experts Forum Thrombosis

INVITED PRESENTATIONS - NATIONAL 1991 Ted Zimmerman Memorial Lecture, American Society for

Hematology


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1992 Gordon Conference on Hemostasis and Thrombosis.

1992 Gordon Conference on Vascular Biology

1992 FASEB Conference on Thrombin.

1992 Cold Spring Harbor Symposium on The Cell Surface.

1992 Thrombosis Sessions, AHA National Meeting.

1993 Gordon Conference on Molecular Pharmacology

1993 Keystone Symposium on Cardiovascular Development

1993 Bugher Lecture, Harvard Medical School

1993 AFCR/ASCI/AAP National Meeting, Program of Excellence Symposium

1993 Restenosis Summit

1993 FASEB Protease Symposium

1993 Gordon Conference on Atherosclerosis

1993 XIVth International Congress on Thrombosis and Haemostasis

1993 American Heart Association Molecular and Cellular Biology of the Vascular Wall.

1993 AHA National Meeting


1994 Keystone Symposium on Endothelial Biology

1994 Keystone Symposium on Proteases

1994 Pine Ridge Conference on Genetics and Thrombosis

1994 Massachusetts General Hospital Cardiology Grand Rounds

1994 Beth Israel Seminars in Medicine Series

1994 FASEB Meeting

1994 Leaders in Life Sciences: A Lecture Series for Venture Capitalists

1994 AHA National Meeting


1995 Distinguished Seminar Series, National Jewish Center, Denver

1995 Year in Medicine - Cardiology at AFCR/ASCI/AAP annual meeting


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1995 American Thoracic Society: Symposium on Molecular and Cellular Biology of G Protein-Coupled Receptors.

1995 Gordon Conference on Atherosclerosis

1995 Gordon Conference on Second Messengers and Protein Phosphorylation

1995 American Society of Hematology (ASH) national meeting

1995 Massachusetts General Hospital Cardiology Grand Rounds

1996 University of Washington, Seattle, Biochemistry Lecture Series

1996 Keystone Conference, Molecular Biology of the Cardiovascular System

1996 AHA Conference on Vascular Biology

1996 Gordon Conference on Hemostasis and Thrombosis


1996 AHA National Meeting, Symposium talk


1997 Molecular Medicine Series Lecture, Duke.

1997 Vascular Biology '97, Symposium talk

1997 Thrombosis Sol Sherry Distinguished Lecture, AHA National Meeting

1997 Woznicki Lecture, Baylor

1998 Keystone Symposium on Specificity in Signal Transduction

1998 Invited speaker, Scripps Vascular Biology Retreat

1998 Vascular Biology ‘98

1998 FASEB ‘98 Symposium on Protease-Activated Receptors

1998 FASEB ‘98 Cardiac Pathology Session, Keynote talk

1998 FASEB ‘98 Symposium on Current Mechanisms of Blood Coagulation

1998 Gordon Conference on Hemostasis


1998 Gordon Conference on Proteolytic Enzymes and Their Inhibitors



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1999 National Academy of Sciences Colloquium on Proteolytic Enzymes and Physiological Regulation

1999 Nossel Memorial Lecture, Columbia University Medical School

1999 Gladstone Institutes Annual Retreat, Guest speaker

1999 Medical Grand Rounds, Stanford

1999 Roon Award Lecture, Scripps

1999 Cardiology Grand Rounds, Washington University, St. Louis

1999 Honors Lecture, NYU

2000 Dueul Conference

2000 Hoeg Award Lecture, American Heart Association

2000 FASEB 2000 Signaling Meeting, Copper Mountain


2000 Keynote Speaker, U. Michigan Ann Arbor Cardiovascular Symposium

2000 UT Southwestern Molecular and Developmental Biology Series

2001 UC Davis Molecular Biology Lecture Series

2001 AAAS Annual Meeting Signaling Symposium

2001 Keynote speaker, University of Wisconsin M.D., Ph.D. program symposium

2001 Keynote, ASBMB FASEB Meeting on Proteolysis and Regulation

2001 FASEB ASIP Symposium, Proteases and Vascular Biology

2001 FASEB ASPET Symposium, G protein-coupled receptors in Endothelial Cell Signaling

2001 American Chemical Society Symposium on PARs

2001 Chiron lecture series

2001 Genentech lecture series

2001 Cold Spring Harbor Meeting on Proteolysis and Biological Control

2001 U Pennsylvania, Thrombosis and Cardiovascular Biology Series

2001 UC Davis, Biochemistry Series


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2001 Temple University, 20th Jeanette Piperno Memorial Lecture

2001 American Heart Association Annual Meeting, Symposium on Tissue Factor Biology

2002 Proteolysis Gordon Conference

2002 Belfer Lecture, Johns Hopkins School of Medicine

2002 Hemostasis Gordon Conference

2002 67th Cold Spring Harbor Symposium on Quantitative Biology

2002 Keynote speaker, Oregon Health Sciences University MSTP Retreat

2002 Russell Ross Memorial Lecture in Vascular Biology, AHA National Meeting

2002 American Society of Hematology National Meeting, Vascular Biology Symposium

2003 Vascular Biology Gordon Conference

2003 Stanford Hematology seminar

2003 Massachusetts General Hospital, Cardiology Grand Rounds

2003 Stuart Stone Memorial Lecture, FASEB Summer Conference on Vascular Biology

2003 American Heart Association Young Investigators Forum Keynote, San Francisco

2003 Evans Lecture, Stanford

2003 Russel Ross Memorial Lecture in Vascular Biology, AHA

2004 University of Washington, Seattle Symposium on Haemostasis

2004 Borun Visiting Professor, UCLA

2004 Bristol-Meyers Squibb Cardiovascular and Metabolic Diseases Colloquium

2004 American Society of Hematology National Meeting, Thrombosis and Vascular Biology Symposium

2005 Platelet Gordon Conference

2005 Vascular Biology Gordon Conference

2005 Atherosclerosis Gordon Conference

2005 FASEB Symposium


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2005 UT Southwestern Biochemistry Series

2005 FASEB Summer Protease meeting

2005 Harvard-MIT Program in Health Sciences and Technology 35th Anniversary

2006 Stanford Cardiovascular Research Series

2006 Keystone meeting on Atherothrombosis Co-organizer

2006 Cleveland Clinic Annual Page Lecture

2006 University of Illinois, Urbana. Molecular Biology Training Program Lecture

2006 Stanley Korsmeyer Award Lecture, ASCI

2006 UNC Chapel Hill, Genetics and Molecular Biology Seminar Series

2006 University of Arkansas Medical Center Physiology Series

2006 Bristol-Meyers Squibb Annual Cardiovascular and Metabolism Awards Research Colloquium

2007 Molecular Pharmacology Gordon Conference Keynote Lecture

2007 Platelet and Megakaryocyte Gordon Conference

2007 UC San Diego Visiting Physician-Scientist Scholar

2007 Mayo Clinic Biochemistry and Molecular Biology Series

2007 American Thoracic Society Annual Meeting

2007 FASEB Hemostasis and Thrombosis Meeting

2007 Massachusetts General Hospital Paul Dudley White Lecture

2007 University of Michigan, Ann Arbor, Frank N. Wilson Visiting Professor

2007 MeHarry Medical School

2008 Keynote, Gordon Research Conference on Plasminogen Activation and Extracellular Proteolysis

2008 Benditt Award Lecture, NAVBO/FASEB annual meeting

2008 University of Pennsylvania Cardiovascular Institute (CVI) inaugural symposium

2008 Keynote, Rockefeller GPCR meeting

2009 University of Delaware

2009 Keystone Conference, Lipid Signaling


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2009 University of Texas Southwestern, University Lecture series

2009 Keynote, AHA-ATVB annual meeting, Washington, D.C.

2009 FASEB Lysophospholipid Mediators

2009 AHA Annual Meeting, Orlando

2009 Columbia University Medical School, Wu Visiting Professor

2010 Keynote Lecture, Keystone GPCR meeting, Breckenridge, CO

2010 Keynote, Hemostasis Gordon Conference, New Hampshire

2010 UC Berkeley Molecular and Cellular Biology Department Seminar

2010 UC Berkeley Nutritional Biochemistry and Toxicology Department Seminar

2011 Molecular Pharmacology Gordon Conference

2011 Metcalfe Lecture, Oregon Health Sciences University

2011 Yale Cardiovascular Research Center Inaugural Symposium

2011 Bristow Lecture, University of Illinois Chicago

2011 FASEB Protease meeting

2012 Extracellular Proteolysis Gordon Conference

2012 Keynote, University of Kentucky Cardiovascular Research Symposium

2012 Distinguished Scientist Lecture, American Heart Association National Meeting

2012 Keynote, 41st Workshop on Hemostasis, Thrombosis and Atherosclerosis, CHoP/UPenn

2013 Deuel Conference Journal of Lipid Research Lecture

2013 Keynote AHA Basic Cardiovascular Sciences Annual Meeting

2013 Keynote Stanford Cardiovascular Institute Annual Retreat

2013 ASBMB Syposium on Proteases

2013 Cotran Lecture, Children's Hospital, Boston

2013 Cardiovascular Grand Rounds, Brigham and Women's Hospital


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2013 Keynote, Annual Earl Davie Symposium, University of Washington

2014 Gordon Research Conference on Extracellular Proteolysis

2014 Arnsdorf Lecture, University of Chicago

2014 Keynote, NAVBO Annual Meeting, Asilomar

2015 Keynote session, Gordon Research Conference on Molecular Pharmacology

2015 Annual student-invited seminar speaker, Pharmacology Graduate Program, UCSD

2016 Duke Cardiovascular Research Series

2016 NYU Karpatkin Lecture

2016 American Society for Hematology Annual Meeting, San Diego

2017 Vascular Cell Biology Gordon Conference

2017 Stanford Drug Discovery Symposium

2017 ASBMB Protease Meeting

2017 American Heart Association Scientific Sessions

INVITED PRESENTATIONS - REGIONAL AND OTHER INVITED PRESENTATIONS 1999 Symposium on Degenerative Diseases, UCSF

1999 Young Presidents Organization, UCSF

2000 PIBS retreat, UCSF

2000 Cardiology Grand Rounds, UCSF

2000 BMS/CVRI retreat, UCSF

2001 Cardiology Grand Rounds/UCSF

2001 Pathology and Laboratory Medicine Grand Rounds/UCSF

2001 UCSF Friday Faculty Research Talk

2002 Bridge Conference, Medicine, UCSF

2002 Angiogenesis Symposium, UCSF

2002 Medical Grand Rounds, San Francisco VA Medical Center

2002 Dean's Series for Medical Students, UCSF


2003 UCSF Dermatology seminar

2003 UCSF Cardiology Grand Rounds


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2004 UCSF Cellular and Molecular Pharmacology Faculty talk

2004 UCSF PIBS retreat

2004 UCSF PSPG retreat

2005 UCSF Biomedical Sciences Program Retreat

2005 UCSF Faculty Research in Progress Parnassus


2006 UCSF Medical Grand Rounds



2008 UCSF Research talk to PIBS students


2008 UCSF Tetrad Retreat

2009 UCSF Tobacco Research and Education Symposium, wrap-up speaker.

2010 UCSF Friday Faculty Research talk



2013 UCSF Biomedical Sciences Program Symposium

GOVERNMENT AND OTHER PROFESSIONAL SERVICE 1995 - NIH-HLBI Peer review committee for Thrombosis SCORs

1996 - NIH-NHLBI Concept review special emphasis panel on emerging areas in thrombosis and hemostasis research.

2003 - 2007 Hemostasis Thrombosis (HT) Study Section, NIH HLBI

2005 - NIH NHLBI Working Group on predicting cardiovascular risk

2006 - NIH NHLBI Working Group on diagnosis and treatment of thrombosis and bleeding

2006 - NIH NHLBI Working Group on inflammation and thrombosis

2006 - NIH NINDS Working Group on stroke

2007 - 2010 NIH National Heart, Lung, Blood Advisory Council

2008 - Review Committee, NHLBI Comprehensive Sickle Cell Centers Program

2009 - NHLBI Translational Research Oversight Committee


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2012 - 2013 NIH SMARTT Program Scientific Review Board

UNIVERSITY AND PUBLIC SERVICE SERVICE ACTIVITIES SUMMARY My main service activities are related to my role as CVRI Director to foster cardiovascular research at UCSF. Activities have included planning the program and design of the Smith Cardiovascular Research Building, securing funding for this $254M project, shepherding its construction, recruiting 18 new faculty members in the past five years, raising funds for the latter, and supporting the development of these faculty members.

UCSF CAMPUSWIDE 1993 - 1994 Curriculum Committee, Biomedical Sciences Program

1993 - Chair of Search Committee, Vascular Biology Recruitment, Gladstone/UCSF

1993 - 2001 Daiichi Research Center Advisory Board

1994 - 1995 Research Committee - Chancellor's Strategic Planning Board

1997 - Chair, Search Committee, Director, Gladstone Institute for Cardiovascular Disease

1997 - Chancellor’s Committee on Industry Relations and Conflicts of Interest

1997 - Mission Bay Task Force

1998 - 1999 Parnassus Planning Committee

1998 - 1999 GCRC Steering Committee

1999 - Advisory Committee, Gladstone Institutes for Cardiovascular Diseases

1999 - HHMI Faculty Candidate Selection Committee

1999 - Search Committee, Assistant Vice Chancellor Industry Relations

1999 - 2000 Mission Bay University-Industry Partnership Committee

2000 - Parnassus Heights Research Space Committee

2000 - Strategic Planning Committee for Clinical Space

2000 - Co-developed proposal for Center for Genetics of Complex Diseases and Therapeutics, UCSF – led to Institute for Human Genetics

2000 - Co-developed proposal for Center for Stem Cell Biology and Tissue Development, UCSF – led to Center for Regenerative Medicine

2002 - Chancellor's Release Space Committee


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2002 - 2005 Parnassus Leadership Council

2002 - 2013 UCSF MSTP Council

2002 - 2004 Executive Committee, Program in Human Genetics, UCSF

2002 - 2004 Search Committee for Director, UCSF Institute for Human Genetics

2002 - Committee to implement Stem Cell Biology and Tissue Development Program, UCSF

2002 - 2004 Search Committee for Director, Developmental and Stem Cell Biology

2002 - 2003 Search Committee for Dean, UCSF School of Medicine

2003 - 2005 Search Committee for Director, Gladstone Institutes of Cardiovascular Disease

2004 - 2005 UCSF Parnassus Leadership Committee

2004 - 2010 UCSF Heart and Vascular Center Executive Committee

2004 - 2010 Co-Chair, Planning Committee, UCSF Cardiovascular Research Building

2005 - 2010 Drove planning and secured funding ($254M) for the new Smith Cardiovascular Research Building, which opened on Mission Bay Campus in 2010

2005 - 2010 Building Committee, UCSF Cardiovascular Research Building

2005 - 2010 UCSF Genentech Hall Governance Committee

2005 - 2010 UCSF Mission Bay Leadership Committee

2006 - SFGH Academic Planning Committee

2006 - CTSA application committee

2007 - UCSF Clinical/Translational cores ad hoc committee

2008 - 2009 Helped explore and implement a new-to-UCSF model for arbitrage of gifts to finance Smith Building, its operations and programs.

2011 - 2012 UCSF, Long Range Development Planning Committee

2014 - 2015 Stewardship Review Committee for Chair, Microbiology and Immunology

2014 - 2015 Co-Chair, Search Committee for Dean of School of Medicine

2015 - 2016 Search Committee for VC Business Development, UCSF

2015 - 2016 ECVP committee to improve UCSF Industry, Technology & Alliances services


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2016 - 2017 Search Committee for Chair, Pediatrics, UCSF

SCHOOL OF MEDICINE 1991 - 2003 Cardiology fellow selection, UCSF- Research Track

1992 - 2007 Board of Directors, Cardiovascular Research and Education Foundation, CVRI/UCSF

1994 - 1997 Executive Committee, CVRI, UCSF

1995 - Department of Medicine Committee on Translational Research

1995 - Search Committee for Reproductive Endocrinology faculty

1995 - Search Committee for Cancer Research Institute faculty

1995 - Ad Hoc Committee of Organized Research Unit representatives for Biomedical Sciences Program

1995 - 2010 Executive Committee, UCSF's Molecular Medicine Program

1996 - 2004 Promotions Subcommittee, Department of Medicine

1997 - present Director, CVRI

1997 - 2007 Executive Committee, UCSF Biomedical Sciences Graduate Program

1997 - Search Committee, Chief, Cardiology Division, UCSF

1997 - present Chair or co-chair of Search Committees for new CVRI Faculty

1998 - 2004 Dean?s Fund Raising Advisory Committee (FRAC)

1999 - Dean?s Advisory Committee on Impacts of Clinical Initiatives

2000 - Chair, Search Committee, Director, Pacific Vascular Research Laboratory

2003 - Advisory Committee, UCSF Prostate Cancer SPORE

2007 - Search Committee, UCSF Chair of Medicine

2007 - 2008 Search Committee, UCSF Chief of Cardiology

2008 - 2009 Search Committee for Dean, UCSF School of Medicine

2009 - Search Committee, UCSF Chief of Pulmonary

2009 - Search Committee, UCSF Radiology, cardiovascular imaging researcher

2009 - 2017 School of Medicine Space Committee

2016 - 2017 Search Committee, UCSF Chair of Pediatrics


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- Ongoing: Multiple PPG and T32 advisory committees, Cardiology fellowship interviewer.

DEPARTMENTAL SERVICE 1997 - present UCSF Cardiovascular Research Institute Director

1997 - present UCSF Cardiovascular Research Institute Faculty search committees chair, co-chair or member

2008 - present UCSF Department of Medicine (Cardiology) and CVRI Presentations to Cardiology Fellowship Applicants on interview days; interview selected applicants

COMMUNITY AND PUBLIC SERVICE 1992 - 1996 Executive Committee, Thrombosis Council, American Heart

Association

1993 - 1996 Program Committee, Thrombosis Council, American Heart Association

1993 - Co-Chair, 1993 Gordon Conference on Atherosclerosis.

1995 - 1997 American Heart Association Katz Prize Committee

1996 - Research Committee, California Affiliate, American Heart Association

1997 - Program Committee, American Heart Association Council on Arteriosclerosis, Thrombosis, and Vascular Biology

1997 - 2001 Chair, IUPHAR Nomenclature Subcommittee on PARs

1997 - Chair, 1997 Gordon Conference on Molecular Pharmacology

2000 - 2003 Myocyte Systems Committee, Alliance for Cell Signaling

2004 - 2008 Search and Screening Committee, National Academy of Sciences, Section 42

2006 - 2016 Scleroderma Research Foundation SAB

2012 - present Leducq Foundation Scientific Review Board, currently Chair

2012 - 2017 Council, American Association of Physicians

2006 - present Chair, Portola Pharmaceuticals SAB

2006 - 2012 Oklahoma Medical Research Foundation SAB


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TEACHING AND MENTORING TEACHING SUMMARY Despite substantial administrative duties, I am able to do some formal teaching. In recent years this has been in the GEMS and BMS225 courses for graduate students and hemostasis/thrombosis-related teaching to medical students as indicated.

FORMAL TEACHING Academic Yr Course No. & Title Teaching Contribution School Class

Size

2006 - present

Cardiology Grand Rounds at UCSF approximately every other year

speaker Medicine

2010 - present

BMS225A Human Disease: Technologies & Biomedical Applications

2-3 contact hours, 3-6 prep hours

Medicine ~30

2010 - present

GEMS Introduction to Human Biology and Medicine

3 contact hours, 3-6 prep hours

Medicine ~30

2010 - 2011 GEMS Demystifying Medicine, Physiology 181

3 contact hours, 3-6 prep hours

Medicine ~30

2014 - Organ Block 2 contact hours, 12 hours prep

Medicine ~150

2015 - 2016 Hemostasis Thrombosis Lecture

2 contact hours, 6 hours prep

Medicine ~150

MENTORING SUMMARY The majority of my teaching and mentoring activities center on training postdoctoral fellows and graduate students in my laboratory. There are 3 structure hours of group teaching weekly (1h journal club and 2h lab meeting), one formal one-on-one hour every two weeks, and more frequent ad hoc and working group meetings. Total contact hours per year are approximately 750. I have supervised approximately 40 postdoctoral fellows, with nearly all going on to research careers in academia or industry. Examples in academia include Mark Kahn (U Penn), JoAnn Trejo (UCSD), Robert Gerszten (MGH/Harvard) Stephen Hammes (U Rochester), Eric Camerer (PARRC-INSERM, Paris), and Ethan Weiss (UCSF). Examples in industry include David Hung (CEO-Medivation), Dan Lerner (CMO-TYRX), Harold Bernstein (Director, Clinical Research & Senor Principal Scientist, Merck), Rajita Pappu (Scientist, Genentech), and Jean Regard (Scientist, Novartis).


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Graduate students are listed above.

PREDOCTORAL STUDENTS SUPERVISED OR MENTORED Dates Name Program or

School Mentor Type Role Current

Position

1994 - 1998 Andrew Connolly

BMS Research/Scholarly Mentor

supervisor Prof. Pathology, Stanford

1998 - 2003 Courtney Griffin

BMS Research/Scholarly Mentor

supervisor Assoc. Member, OMRF, U Oklahoma Health Science Center

2000 - 2005 David Willison MSTP Research/Scholarly Mentor

supervisor Research Fellow, Child Psychiatry, UCLA

2008 - 2013 Arif Hussain MSTP Research/Scholarly Mentor

supervisor Medical Student

2009 - 2015 Adrian Barker BMS Research/Scholarly Mentor

supervisor BMS student

2012 - 2016 Eamon Balouch

UC Davis MSTP

Research/Scholarly Mentor

supervisor UC Davis MSTP student

POSTDOCTORAL FELLOWS AND RESIDENTS MENTORED Dates Name Fellow Mentor Role Faculty Role Current

Position

- Research/Scholarly Mentor,Project Mentor,Career Mentor

~44 postdoctoral fellows trained-- see narrative

FACULTY MENTORING Dates Name Position while

Mentored Mentor Type Mentoring Role Current

Position


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Dates Name Position while Mentored

Mentor Type Mentoring Role Current Position

- Research/Scholarly Mentor,Project Mentor,Career Mentor

informal mentoring of CVRI junior faculty-- ongoing

VISITING FACULTY MENTORED 1992 - 1993 Prof Scot Soifer UCSF

1993 - 1994 Prof israel Charo UCSF/Gladstone

1998 - 1999 Prof Eric Rondeau U. Curie, Paris

2011 - 2012 Prof Erica DeCandia Catholic U. Hospital, Rome

RESEARCH AND CREATIVE ACTIVITIES RESEARCH AND CREATIVE ACTIVITIES SUMMARY Our laboratory seeks to define signaling mechanisms that govern cardiovascular biology and disease. Current areas of focus include: 1) Protease-Activated Receptors (PARs). a) Structure-Function. Our laboratory discovered and characterized PARs, a family of GPCRs that permit thrombin and related proteases to regulate the behavior of platelets and other cells. Mutational and biochemical studies suggest that PARs are activated by an elegant proteolytic mechanism. Thrombin cleaves the N-terminal exodomain of PAR1 to create a new N-terminus that then serves as a tethered peptide agonist, binding intramolecularly to the receptor's heptahelical bundle to effect transmembrane movement and G protein activation. While a substantial body of data from mutational and biochemical studies supports this model, an on-state crystal structure of PAR1 that confirms the tethered ligand mechanism and reveals how the tethered ligand docks and triggers transmembrane signaling is needed. In collaboration with Brian Kobilka's laboratory, we recently solved an off-state structure of PAR1 in complex with its antagonist vorapaxar. The structure explained the effectively irreversible action of vorapaxar and suggested a novel drug entry route and a possible contribution of entry kinetics to drug specificity –– areas of current inquiry. More importantly, the know-how acquired in solving this off-state structure has positioned us to take on the challenge of solving the PAR1 on-state structure. PAR1 couples to Gi, Gq and G12. We seek to solve structures of activated PAR1 in complex with these three G proteins. In addition to revealing the details of tethered ligand docking and transmembrane signaling, these structures will reveal how a single GPCR can couple to distinct G proteins; in addition to revealing basic mechanisms, the answer will likely provide structural insight into the mechanism of biased agonism. b) Physiology. Mammals have 4 PARs. Together with the coagulation cascade, these receptors link tissue injury to cellular responses that regulate blood clotting, inflammation, pain sensation, and perhaps cytoprotection and repair. PARs are necessary for platelet activation by thrombin, and the PAR1 antagonist vorapaxar was recently FDA-approved to prevent myocardial infarction and ischemic stroke in selected patients with known atherothrombotic disease (albeit at a cost of increased bleeding risk). Current work in this area focuses on better


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defining the roles of PAR function in platelets and endothelial cells in hemostasis and vascular integrity in mouse models of spontaneous bleeding. c) Embryonic Development. PARs also contribute to embryonic development. Par1 function in endothelial cells is appears to be necessary for normal vascular integrity in mouse embryos. Par2 appears to be necessary for normal placentation. Work to understand the mechanisms underlying these phenotypes is ongoing. d) Epithelial Biology. Recent work in the lab suggests that a local network comprised of membrane-tethered proteases matriptase and prostasin, their inhibitors, and Par2 may regulate epithelial structure and function. These molecules are co-expressed in many epithelial tissues from gut to glands to skin, and mouse and human genetic studies suggest possible roles in regulating epithelial integrity and other functions. We are using genetic and advanced microscopy to define the detailed roles of matriptase and Par2 in the periderm (apical) and basal layers of the skin of zebrafish embryos as a model epithelium. Our studies support an unexpected role in regulating epithelial cell extrusion, cell-cell junctions, proliferation and survival as well as epithelial-triggered inflammation. 2) Inflammation and Repair We have invested in developing a zebrafish model of response to vascular injury that allows visualization of hemostasis, neutrophil and macrophage recruitment and egress, resolution of thrombi, and endothelial repair with restoration of blood flow all within 24 h. The model is high-content and high-throughput. At the same time, we have developed methodology for F0 knockouts of genes in zebrafish that enables immediate analysis of loss of function of genes of interest. We are using this F0 knockout system to evaluate the importance of different cell types and pathways in this model, with focus on resolution of inflammation. We expect the general F0 knockout approach to be widely applicable as a complement to morpholinos and stable knockouts, and we are currently using it in other moderate throughput screening applications. 3) Evaluation of Intrinsic Pathway Function in Human Hemostasis and Thrombosis Human genetics and animal model studies support a role for coagulation factor XIa in thrombosis and raise the possibility that inhibition of FXIa might prevent thrombosis with less bleeding risk than current agents. Toward testing this hypothesis and in collaboration with Pfizer's Center for Therapeutic Innovation, we generated a fully human effector null IgG that is FXIa-specific and blocks thrombosis in two animal models without a detectable effect on hemostasis. A crystal structure of the FXIa-antibody complex confirmed occupancy of the FXIa active site. Efforts to out-license this molecule are in progress. Additionally, with the ultimate goal of developing preclinical models that predict bleeding risk in humans, we have developed a mouse model that features spontaneous GI bleeding that is highly platelet and coagulation-dependent. We are testing the effect of FXI and PAR3 deficiencies in this model to ascertain whether it might predict bleeding liabilities not detected in standard bleeding time another induced-bleeding models.

RESEARCH AWARDS - CURRENT 1. NIH HL07731 PI 50 % effort Coughlin (PI) NIH/NHLBI 09/01/2012 08/31/2017


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Molecular and Cellular Mechanisms of Cardiovascular Disease

$ 412450 direct/yr 1

T32 training grant. Renewal will be funded. 2. R01 HL121387 Corresponding PI (other PI

is B. Kobilka) Coughlin (PI)

NIH/NHLBI 01/15/2014 12/31/2017 Structural Basis of Protease-Activated Receptor

Function $ 562,704 direct/yr 1

Seeks to solve on-state structure of PAR1 to reveal mechanism of tethered ligand docking and basis for G protein specificity

3. R35 HL135755 PI 50 % effort Coughlin (PI) NIH/NHLBI 2/14/2017 12/312023 Structure-Function and Roles of Protease-Activated

Receptors $ ~500000 direct/yr 1

$ ~4200000 total

RESEARCH AWARDS - PAST 1. UCSF Pfizer CTI PI Coughlin (PI) Pfizer 08/11/2014 08/15/2016 A Clinical Probe to Define the Role of Novel

Antithrombotic Target in Humans $ 52276 direct/yr 1

Probes role of unprecedented target in human thrombosis 2. R01HL054737 PI Coughlin (PI) NIH/NHLBI 06/30/2013 04/30/2017 Molecular Genetics of Cardiac Cell Differentiation $ 238000 direct/yr

1

Zebrafish models of heart and vascular development 3. U54 HL119893 Co-PI of UCSF

Component with June Lee Palazzolo M (PI)

NIH/NHLBI 01/2014 01/2019 NHLBI Center for Accelerated Innovation. Provides incubator funding to projects with translational promise in CV arena. No funds to

Coughlin lab. Transferred PI to Dr. Lee 4.


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Additional grant funding history available upon request. Continuous NIH funding from 1980s-

2017.

PEER REVIEWED PUBLICATIONS 1. Coughlin SR, Moskowitz MA, Zetter BR, Antoniades HN, Levine L. Platelet-dependent

stimulation of prostacyclin synthesis by platelet-derived growth factor. Nature. 1980 Dec 11; 288(5791):600-2. PMID: 7003399

2. Coughlin SR, Moskowitz MA, Antoniades HN, Levine L. Serotonin receptor-mediated stimulation of bovine smooth muscle cell prostacyclin synthesis and its modulation by platelet-derived growth factor. Proc Natl Acad Sci U S A. 1981 Nov; 78(11):7134-8. PMID: 7031670

3. Glassberg, M.K., Bern, M.M., Coughlin, S.R., Haudenschild, C.C., Hoyer, L.W., Antoniades, H.N., and Zetter, B.R. (1982) Cultured endothelial cells derived from human iliac arteries. In Vitro l8(l0):859-866.

4. Coughlin SR, Moskowitz MA, Levine L. Identification of a serotonin type 2 receptor linked to prostacyclin synthesis in vascular smooth muscle cells. Biochem Pharmacol. 1984 Feb 15; 33(4):692-5. PMID: 6322808

5. Garrett JS, Coughlin SR, Niman HL, Tremble PM, Giels GM, Williams LT. Blockade of autocrine stimulation in simian sarcoma virus-transformed cells reverses down-regulation of platelet-derived growth factor receptors. Proc Natl Acad Sci U S A. 1984 Dec; 81(23):7466-70. PMID: 6095298

6. Coughlin SR, Lee WM, Williams PW, Giels GM, Williams LT. c-myc gene expression is stimulated by agents that activate protein kinase C and does not account for the mitogenic effect of PDGF. Cell. 1985 Nov; 43(1):243-51. PMID: 3000601

7. Nemecek GM, Coughlin SR, Handley DA, Moskowitz MA. Stimulation of aortic smooth muscle cell mitogenesis by serotonin. Proc Natl Acad Sci U S A. 1986 Feb; 83(3):674-8. PMID: 3456163

8. Simpson P, Bishopric N, Coughlin S, Karliner J, Ordahl C, Starksen N, Tsao T, White N, Williams L. Dual trophic effects of the alpha 1-adrenergic receptor in cultured neonatal rat heart muscle cells. J Mol Cell Cardiol. 1986 Nov; 18 Suppl 5:45-58. PMID: 3027351

9. Starksen NF, Simpson PC, Bishopric N, Coughlin SR, Lee WM, Escobedo JA, Williams LT. Cardiac myocyte hypertrophy is associated with c-myc protooncogene expression. Proc Natl Acad Sci U S A. 1986 Nov; 83(21):8348-50. PMID: 3022291

10. Letterio JJ, Coughlin SR, Williams LT. Pertussis toxin-sensitive pathway in the stimulation of c-myc expression and DNA synthesis by bombesin. Science. 1986 Nov 28; 234(4780):1117-9. PMID: 3465038

11. Kacich RL, Williams LT, Coughlin SR. Arachidonic acid and cyclic adenosine monophosphate stimulation of c-fos expression by a pathway independent of phorbol ester-sensitive protein kinase C. Mol Endocrinol. 1988 Jan; 2(1):73-7. PMID: 2840568


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12. Coughlin SR, Barr PJ, Cousens LS, Fretto LJ, Williams LT. Acidic and basic fibroblast growth factors stimulate tyrosine kinase activity in vivo. J Biol Chem. 1988 Jan 15; 263(2):988-93. PMID: 2447083

13. Escobedo JA, Navankasatussas S, Cousens LS, Coughlin SR, Bell GI, Williams LT. A common PDGF receptor is activated by homodimeric A and B forms of PDGF. Science. 1988 Jun 10; 240(4858):1532-4. PMID: 2836953

14. Kavanaugh WM, Williams LT, Ives HE, Coughlin SR. Serotonin-induced deoxyribonucleic acid synthesis in vascular smooth muscle cells involves a novel, pertussis toxin-sensitive pathway. Mol Endocrinol. 1988 Jul; 2(7):599-605. PMID: 2842665

15. Coughlin SR, Keating MT. The platelet-derived growth factor system. Cancer Treat Res. 1989; 47:169-76. PMID: 2576996

16. Coughlin SR, Escobedo JA, Williams LT. Role of phosphatidylinositol kinase in PDGF receptor signal transduction. Science. 1989 Mar 3; 243(4895):1191-4. PMID: 2466336

17. Vu TK, Hung DT, Wheaton VI, Coughlin SR. Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation. Cell. 1991 Mar 22; 64(6):1057-68. PMID: 1672265

18. Lanza F, Wolf D, Fox CF, Kieffer N, Seyer JM, Fried VA, Coughlin SR, Phillips DR, Jennings LK. cDNA cloning and expression of platelet p24/CD9. Evidence for a new family of multiple membrane-spanning proteins. J Biol Chem. 1991 Jun 5; 266(16):10638-45. PMID: 2037603

19. Liu LW, Vu TK, Esmon CT, Coughlin SR. The region of the thrombin receptor resembling hirudin binds to thrombin and alters enzyme specificity. J Biol Chem. 1991 Sep 15; 266(26):16977-80. PMID: 1654318

20. Nelken NA, Coughlin SR, Gordon D, Wilcox JN. Monocyte chemoattractant protein-1 in human atheromatous plaques. J Clin Invest. 1991 Oct; 88(4):1121-7. PMID: 1843454

21. Vu TK, Wheaton VI, Hung DT, Charo I, Coughlin SR. Domains specifying thrombin-receptor interaction. Nature. 1991 Oct 17; 353(6345):674-7. PMID: 1717851

22. Hung DT, Vu TH, Nelken NA, Coughlin SR. Thrombin-induced events in non-platelet cells are mediated by the unique proteolytic mechanism established for the cloned platelet thrombin receptor. J Cell Biol. 1992 Feb; 116(3):827-32. PMID: 1309820

23. Hung DT, Vu TK, Wheaton VI, Charo IF, Nelken NA, Esmon N, Esmon CT, Coughlin SR. (1992) "Mirror image" antagonists of thrombin-induced platelet activation based on thrombin receptor structure.? J Clin Invest. 89:444-50. PMID: 1310695

24. Hung DT, Vu TK, Wheaton VI, Ishii K, Coughlin SR. Cloned platelet thrombin receptor is necessary for thrombin-induced platelet activation. J Clin Invest. 1992 Apr; 89(4):1350-3. PMID: 1313452

25. Scarborough RM, Naughton MA, Teng W, Hung DT, Rose J, Vu TK, Wheaton VI, Turck CW, Coughlin SR. Tethered ligand agonist peptides. Structural requirements for thrombin receptor activation reveal mechanism of proteolytic unmasking of agonist function. J Biol Chem. 1992 Jul 5; 267(19):13146-9. PMID: 1320011


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26. Nelken NA, Soifer SJ, O'Keefe J, Vu TK, Charo IF, Coughlin SR. Thrombin receptor expression in normal and atherosclerotic human arteries. J Clin Invest. 1992 Oct; 90(4):1614-21. PMID: 1328304

27. Hung DT, Wong YH, Vu TK, Coughlin SR. The cloned platelet thrombin receptor couples to at least two distinct effectors to stimulate phosphoinositide hydrolysis and inhibit adenylyl cyclase. J Biol Chem. 1992 Oct 15; 267(29):20831-4. PMID: 1328213

28. McNamara CA, Sarembock IJ, Gimple LW, Fenton JW, Coughlin SR, Owens GK. Thrombin stimulates proliferation of cultured rat aortic smooth muscle cells by a proteolytically activated receptor. J Clin Invest. 1993 Jan; 91(1):94-8. PMID: 8380817

29. Ishii K, Hein L, Kobilka B, Coughlin SR. Kinetics of thrombin receptor cleavage on intact cells. Relation to signaling. J Biol Chem. 1993 May 5; 268(13):9780-6. PMID: 7683662

30. Soifer SJ, Peters KG, O'Keefe J, Coughlin SR. Disparate temporal expression of the prothrombin and thrombin receptor genes during mouse development. Am J Pathol. 1994 Jan; 144(1):60-9. PMID: 8291612

31. Wilcox JN, Nelken NA, Coughlin SR, Gordon D, Schall TJ. Local expression of inflammatory cytokines in human atherosclerotic plaques. J Atheroscler Thromb. 1994; 1 Suppl 1:S10-3. PMID: 9222884

32. Ishii K, Chen J, Ishii M, Koch WJ, Freedman NJ, Lefkowitz RJ, Coughlin SR. Inhibition of thrombin receptor signaling by a G-protein coupled receptor kinase. Functional specificity among G-protein coupled receptor kinases. J Biol Chem. 1994 Jan 14; 269(2):1125-30. PMID: 8288570

33. Mathews II, Padmanabhan KP, Ganesh V, Tulinsky A, Ishii M, Chen J, Turck CW, Coughlin SR, Fenton JW. Crystallographic structures of thrombin complexed with thrombin receptor peptides: existence of expected and novel binding modes. Biochemistry. 1994 Mar 22; 33(11):3266-79. PMID: 8136362

34. Charo IF, Myers SJ, Herman A, Franci C, Connolly AJ, Coughlin SR. Molecular cloning and functional expression of two monocyte chemoattractant protein 1 receptors reveals alternative splicing of the carboxyl-terminal tails. Proc Natl Acad Sci U S A. 1994 Mar 29; 91(7):2752-6. PMID: 8146186

35. Gerszten RE, Chen J, Ishii M, Ishii K, Wang L, Nanevicz T, Turck CW, Vu TK, Coughlin SR. Specificity of the thrombin receptor for agonist peptide is defined by its extracellular surface. Nature. 1994 Apr 14; 368(6472):648-51. PMID: 8145852

36. Chen J, Ishii M, Wang L, Ishii K, Coughlin SR. Thrombin receptor activation. Confirmation of the intramolecular tethered liganding hypothesis and discovery of an alternative intermolecular liganding mode. J Biol Chem. 1994 Jun 10; 269(23):16041-5. PMID: 8206902

37. Hein L, Ishii K, Coughlin SR, Kobilka BK. Intracellular targeting and trafficking of thrombin receptors. A novel mechanism for resensitization of a G protein-coupled receptor. J Biol Chem. 1994 Nov 4; 269(44):27719-26. PMID: 7961693

38. Ishii K, Gerszten R, Zheng YW, Welsh JB, Turck CW, Coughlin SR. Determinants of thrombin receptor cleavage. Receptor domains involved, specificity, and role of the P3 aspartate. J Biol Chem. 1995 Jul 7; 270(27):16435-40. PMID: 7608215


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39. Nanevicz T, Ishii M, Wang L, Chen M, Chen J, Turck CW, Cohen FE, Coughlin SR. Mechanisms of thrombin receptor agonist specificity. Chimeric receptors and complementary mutations identify an agonist recognition site. J Biol Chem. 1995 Sep 15; 270(37):21619-25. PMID: 7665575

40. Chen J, Bernstein HS, Chen M, Wang L, Ishii M, Turck CW, Coughlin SR. Tethered ligand library for discovery of peptide agonists. J Biol Chem. 1995 Oct 6; 270(40):23398-401. PMID: 7559498

41. Isik FF, Coughlin SR, Nelken NA, Clowes AW, Gordon D. JE gene expression in an animal model of acute arterial graft rejection. J Surg Res. 1996 Jan; 60(1):224-31. PMID: 8592418

42. Nanevicz T, Wang L, Chen M, Ishii M, Coughlin SR. Thrombin receptor activating mutations. Alteration of an extracellular agonist recognition domain causes constitutive signaling. J Biol Chem. 1996 Jan 12; 271(2):702-6. PMID: 8557676

43. Bohm SK, Kong W, Bromme D, Smeekens SP, Anderson DC, Connolly A, Kahn M, Nelken NA, Coughlin SR, Payan DG, Bunnett NW. Molecular cloning, expression and potential functions of the human proteinase-activated receptor-2. Biochem J. 1996 Mar 15; 314 ( Pt 3):1009-16. PMID: 8615752

44. Kahn M, Ishii K, Kuo WL, Piper M, Connolly A, Shi YP, Wu R, Lin CC, Coughlin SR. Conserved structure and adjacent location of the thrombin receptor and protease-activated receptor 2 genes define a protease-activated receptor gene cluster. Mol Med. 1996 May; 2(3):349-57. PMID: 8784787

45. Brown JL, Stowers L, Baer M, Trejo J, Coughlin S, Chant J. Human Ste20 homologue hPAK1 links GTPases to the JNK MAP kinase pathway. Curr Biol. 1996 May 1; 6(5):598-605. PMID: 8805275

46. Connolly AJ, Ishihara H, Kahn ML, Farese RV, Coughlin SR. Role of the thrombin receptor in development and evidence for a second receptor. Nature. 1996 Jun 6; 381(6582):516-9. PMID: 8632823

47. Lerner DJ, Chen M, Tram T, Coughlin SR. Agonist recognition by proteinase-activated receptor 2 and thrombin receptor. Importance of extracellular loop interactions for receptor function. J Biol Chem. 1996 Jun 14; 271(24):13943-7. PMID: 8662993

48. Kranzhöfer R, Clinton SK, Ishii K, Coughlin SR, Fenton JW, Libby P. Thrombin potently stimulates cytokine production in human vascular smooth muscle cells but not in mononuclear phagocytes. Circ Res. 1996 Aug; 79(2):286-94. PMID: 8756006

49. Trejo J, Connolly AJ, Coughlin SR. The cloned thrombin receptor is necessary and sufficient for activation of mitogen-activated protein kinase and mitogenesis in mouse lung fibroblasts. Loss of responses in fibroblasts from receptor knockout mice. J Biol Chem. 1996 Aug 30; 271(35):21536-41. PMID: 8702939

50. Franci C, Gosling J, Tsou CL, Coughlin SR, Charo IF. Phosphorylation by a G protein-coupled kinase inhibits signaling and promotes internalization of the monocyte chemoattractant protein-1 receptor. Critical role of carboxyl-tail serines/threonines in receptor function. J Immunol. 1996 Dec 15; 157(12):5606-12. PMID: 8955213

51. Shapiro MJ, Trejo J, Zeng D, Coughlin SR. Role of the thrombin receptor's cytoplasmic tail in intracellular trafficking. Distinct determinants for agonist-triggered versus tonic internalization and intracellular localization. J Biol Chem. 1996 Dec 20; 271(51):32874-80. PMID: 8955127


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52. Bernstein HS, Coughlin SR. Pombe Cdc5-related protein. A putative human transcription factor implicated in mitogen-activated signaling. J Biol Chem. 1997 Feb 28; 272(9):5833-7. PMID: 9038199

53. Molino M, Bainton DF, Hoxie JA, Coughlin SR, Brass LF. Thrombin receptors on human platelets. Initial localization and subsequent redistribution during platelet activation. J Biol Chem. 1997 Feb 28; 272(9):6011-7. PMID: 9038223

54. Verrall S, Ishii M, Chen M, Wang L, Tram T, Coughlin SR. The thrombin receptor second cytoplasmic loop confers coupling to Gq-like G proteins in chimeric receptors. Additional evidence for a common transmembrane signaling and G protein coupling mechanism in G protein-coupled receptors. J Biol Chem. 1997 Mar 14; 272(11):6898-902. PMID: 9054376

55. Ishihara H, Connolly AJ, Zeng D, Kahn ML, Zheng YW, Timmons C, Tram T, Coughlin SR. Protease-activated receptor 3 is a second thrombin receptor in humans. Nature. 1997 Apr 3; 386(6624):502-6. PMID: 9087410

56. Connolly AJ, Suh DY, Hunt TK, Coughlin SR. Mice lacking the thrombin receptor, PAR1, have normal skin wound healing. Am J Pathol. 1997 Nov; 151(5):1199-204. PMID: 9358744

57. An S, Bleu T, Huang W, Hallmark OG, Coughlin SR, Goetzl EJ. Identification of cDNAs encoding two G protein-coupled receptors for lysosphingolipids. FEBS Lett. 1997 Nov 17; 417(3):279-82. PMID: 9409733

58. Bernstein HS, Coughlin SR. A mammalian homolog of fission yeast Cdc5 regulates G2 progression and mitotic entry. J Biol Chem. 1998 Feb 20; 273(8):4666-71. PMID: 9468527

59. Ishihara H, Zeng D, Connolly AJ, Tam C, Coughlin SR. Antibodies to protease-activated receptor 3 inhibit activation of mouse platelets by thrombin. Blood. 1998 Jun 1; 91(11):4152-7. PMID: 9596661

60. Kahn ML, Zheng YW, Huang W, Bigornia V, Zeng D, Moff S, Farese RV, Tam C, Coughlin SR. A dual thrombin receptor system for platelet activation. Nature. 1998 Aug 13; 394(6694):690-4. PMID: 9716134

61. Kahn ML, Hammes SR, Botka C, Coughlin SR. Gene and locus structure and chromosomal localization of the protease-activated receptor gene family. J Biol Chem. 1998 Sep 4; 273(36):23290-6. PMID: 9722561

62. Shapiro MJ, Coughlin SR. Separate signals for agonist-independent and agonist-triggered trafficking of protease-activated receptor 1. J Biol Chem. 1998 Oct 30; 273(44):29009-14. PMID: 9786906

63. Trejo J, Hammes SR, Coughlin SR. Termination of signaling by protease-activated receptor-1 is linked to lysosomal sorting. Proc Natl Acad Sci U S A. 1998 Nov 10; 95(23):13698-702. PMID: 9811863

64. Trejo J, Coughlin SR. The cytoplasmic tails of protease-activated receptor-1 and substance P receptor specify sorting to lysosomes versus recycling. J Biol Chem. 1999 Jan 22; 274(4):2216-24. PMID: 9890984

65. Hammes SR, Coughlin SR. Protease-activated receptor-1 can mediate responses to SFLLRN in thrombin-desensitized cells: evidence for a novel mechanism for preventing or terminating signaling by PAR1's tethered ligand. Biochemistry. 1999 Feb 23; 38(8):2486-93. PMID: 10029543


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66. Kahn ML, Nakanishi-Matsui M, Shapiro MJ, Ishihara H, Coughlin SR. Protease-activated receptors 1 and 4 mediate activation of human platelets by thrombin. J Clin Invest. 1999 Mar; 103(6):879-87. PMID: 10079109

67. Sambrano GR, Coughlin SR. The carboxyl tail of protease-activated receptor-1 is required for chemotaxis. Correlation of signal termination and directional migration. J Biol Chem. 1999 Jul 16; 274(29):20178-84. PMID: 10400633

68. Hammes SR, Shapiro MJ, Coughlin SR. Shutoff and agonist-triggered internalization of protease-activated receptor 1 can be separated by mutation of putative phosphorylation sites in the cytoplasmic tail. Biochemistry. 1999 Jul 20; 38(29):9308-16. PMID: 10413505

69. Kahn ML, Diacovo TG, Bainton DF, Lanza F, Trejo J, Coughlin SR. Glycoprotein V-deficient platelets have undiminished thrombin responsiveness and Do not exhibit a Bernard-Soulier phenotype. Blood. 1999 Dec 15; 94(12):4112-21. PMID: 10590056

70. Cunningham MA, Rondeau E, Chen X, Coughlin SR, Holdsworth SR, Tipping PG. Protease-activated receptor 1 mediates thrombin-dependent, cell-mediated renal inflammation in crescentic glomerulonephritis. J Exp Med. 2000 Feb 7; 191(3):455-62. PMID: 10662791

71. Sambrano GR, Huang W, Faruqi T, Mahrus S, Craik C, Coughlin SR. Cathepsin G activates protease-activated receptor-4 in human platelets. J Biol Chem. 2000 Mar 10; 275(10):6819-23. PMID: 10702240

72. Nakanishi-Matsui M, Zheng YW, Sulciner DJ, Weiss EJ, Ludeman MJ, Coughlin SR. PAR3 is a cofactor for PAR4 activation by thrombin. Nature. 2000 Apr 6; 404(6778):609-13. PMID: 10766244

73. Camerer E, Huang W, Coughlin SR. Tissue factor- and factor X-dependent activation of protease-activated receptor 2 by factor VIIa. Proc Natl Acad Sci U S A. 2000 May 9; 97(10):5255-60. PMID: 10805786

74. Faruqi TR, Weiss EJ, Shapiro MJ, Huang W, Coughlin SR. Structure-function analysis of protease-activated receptor 4 tethered ligand peptides. Determinants of specificity and utility in assays of receptor function. J Biol Chem. 2000 Jun 30; 275(26):19728-34. PMID: 10779527

75. Shapiro MJ, Weiss EJ, Faruqi TR, Coughlin SR. Protease-activated receptors 1 and 4 are shut off with distinct kinetics after activation by thrombin. J Biol Chem. 2000 Aug 18; 275(33):25216-21. PMID: 10837487

76. Takeuchi T, Harris JL, Huang W, Yan KW, Coughlin SR, Craik CS. Cellular localization of membrane-type serine protease 1 and identification of protease-activated receptor-2 and single-chain urokinase-type plasminogen activator as substrates. J Biol Chem. 2000 Aug 25; 275(34):26333-42. PMID: 10831593

77. Trejo J, Altschuler Y, Fu HW, Mostov KE, Coughlin SR. Protease-activated receptor-1 down-regulation: a mutant HeLa cell line suggests novel requirements for PAR1 phosphorylation and recruitment to clathrin-coated pits. J Biol Chem. 2000 Oct 6; 275(40):31255-65. PMID: 10893235

78. Lindner JR, Kahn ML, Coughlin SR, Sambrano GR, Schauble E, Bernstein D, Foy D, Hafezi-Moghadam A, Ley K. Delayed onset of inflammation in protease-activated receptor-2-deficient mice. J Immunol. 2000 Dec 1; 165(11):6504-10. PMID: 11086091


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79. Griffin CT, Srinivasan Y, Zheng YW, Huang W, Coughlin SR. A role for thrombin receptor signaling in endothelial cells during embryonic development. Science. 2001 Aug 31; 293(5535):1666-70. PMID: 11533492

80. Sambrano GR, Weiss EJ, Zheng YW, Huang W, Coughlin SR. Role of thrombin signalling in platelets in haemostasis and thrombosis. Nature. 2001 Sep 6; 413(6851):74-8. PMID: 11544528

81. Camerer E, Kataoka H, Kahn M, Lease K, Coughlin SR. Genetic evidence that protease-activated receptors mediate factor Xa signaling in endothelial cells. J Biol Chem. 2002 May 3; 277(18):16081-7. PMID: 11850418

82. Weiss EJ, Hamilton JR, Lease KE, Coughlin SR. Protection against thrombosis in mice lacking PAR3. Blood. 2002 Nov 1; 100(9):3240-4. PMID: 12384423

83. Eisenhaure TM, Francis SA, Willison LD, Coughlin SR, Lerner DJ. The Rho guanine nucleotide exchange factor Lsc homo-oligomerizes and is negatively regulated through domains in its carboxyl terminus that are absent in novel splenic isoforms. J Biol Chem. 2003 Aug 15; 278(33):30975-84. PMID: 12773540

84. Kataoka H, Hamilton JR, McKemy DD, Camerer E, Zheng YW, Cheng A, Griffin C, Coughlin SR. Protease-activated receptors 1 and 4 mediate thrombin signaling in endothelial cells. Blood. 2003 Nov 1; 102(9):3224-31. PMID: 12869501

85. Camerer E, Duong DN, Hamilton JR, Coughlin SR. Combined deficiency of protease-activated receptor-4 and fibrinogen recapitulates the hemostatic defect but not the embryonic lethality of prothrombin deficiency. Blood. 2004 Jan 1; 103(1):152-4. PMID: 14504091

86. Ludeman MJ, Zheng YW, Ishii K, Coughlin SR. Regulated shedding of PAR1 N-terminal exodomain from endothelial cells. J Biol Chem. 2004 Apr 30; 279(18):18592-9. PMID: 14982936

87. Camerer E, Qazi AA, Duong DN, Cornelissen I, Advincula R, Coughlin SR. Platelets, protease-activated receptors, and fibrinogen in hematogenous metastasis. Blood. 2004 Jul 15; 104(2):397-401. PMID: 15031212

88. Hamilton JR, Cornelissen I, Coughlin SR. Impaired hemostasis and protection against thrombosis in protease-activated receptor 4-deficient mice is due to lack of thrombin signaling in platelets. J Thromb Haemost. 2004 Aug; 2(8):1429-35. PMID: 15304051

89. Ludeman MJ, Kataoka H, Srinivasan Y, Esmon NL, Esmon CT, Coughlin SR. PAR1 cleavage and signaling in response to activated protein C and thrombin. J Biol Chem. 2005 Apr 1; 280(13):13122-8. PMID: 15665002

90. Ruppel* KM, Willison* D, Kataoka H, Wang A, Zheng YW, Cornelissen I, Yin L, Xu SM, Coughlin SR. Essential role for Galpha13 in endothelial cells during embryonic development. Proc Natl Acad Sci U S A. 2005 Jun 7; 102(23):8281-6. PMID: 15919816 *co-first

91. Su X, Camerer E, Hamilton JR, Coughlin SR, Matthay MA. Protease-activated receptor-2 activation induces acute lung inflammation by neuropeptide-dependent mechanisms. J Immunol. 2005 Aug 15; 175(4):2598-605. PMID: 16081834


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92. Camerer E, Cornelissen I, Kataoka H, Duong DN, Zheng YW, Coughlin SR. Roles of protease-activated receptors in a mouse model of endotoxemia. Blood. 2006 May 15; 107(10):3912-21. PMID: 16434493

93. De Candia E, Pecci A, Ciabattoni G, De Cristofaro R, Rutella S, Yao-Wu Z, Lazzareschi I, Landolfi R, Coughlin S, Balduini CL. Defective platelet responsiveness to thrombin and protease-activated receptors agonists in a novel case of gray platelet syndrome: correlation between the platelet defect and the alpha-granule content in the patient and four relatives. J Thromb Haemost. 2007 Mar; 5(3):551-9. PMID: 17137471

94. Vandendries ER, Hamilton JR, Coughlin SR, Furie B, Furie BC. Par4 is required for platelet thrombus propagation but not fibrin generation in a mouse model of thrombosis. Proc Natl Acad Sci U S A. 2007 Jan 2; 104(1):288-92. PMID: 17190826

95. Pappu R*, Schwab SR*, Cornelissen I, Pereira JP, Regard JB, Xu Y, Camerer E, Zheng YW, Huang Y, Cyster JG**, Coughlin SR**. Promotion of lymphocyte egress into blood and lymph by distinct sources of sphingosine-1-phosphate. Science. 2007 Apr 13; 316(5822):295-8. PMID: 17363629 *co-first; **co-corresponding

96. Cottrell GS, Amadesi S, Pikios S, Camerer E, Willardsen JA, Murphy BR, Caughey GH, Wolters PJ, Coughlin SR, Peterson A, Knecht W, Pothoulakis C, Bunnett NW, Grady EF. Protease-activated receptor 2, dipeptidyl peptidase I, and proteases mediate Clostridium difficile toxin A enteritis. Gastroenterology. 2007 Jun; 132(7):2422-37. PMID: 17570216

97. Sood R, Zogg M, Westrick RJ, Guo YH, Kerschen EJ, Girardi G, Salmon JE, Coughlin SR, Weiler H. Fetal gene defects precipitate platelet-mediated pregnancy failure in factor V Leiden mothers. J Exp Med. 2007 May 14; 204(5):1049-56. PMID: 17438064

98. Regard JB, Kataoka H, Cano DA, Camerer E, Yin L, Zheng YW, Scanlan TS, Hebrok M, Coughlin SR. Probing cell type-specific functions of Gi in vivo identifies GPCR regulators of insulin secretion. J Clin Invest. 2007 Dec; 117(12):4034-43. PMID: 17992256

99. Cho J, Furie BC, Coughlin SR, Furie B. A critical role for extracellular protein disulfide isomerase during thrombus formation in mice. J Clin Invest. 2008 Mar; 118(3):1123-31. PMID: 18292814

100. Sood R, Sholl L, Isermann B, Zogg M, Coughlin SR, Weiler H. Maternal Par4 and platelets contribute to defective placenta formation in mouse embryos lacking thrombomodulin. Blood. 2008 Aug 1; 112(3):585-91. PMID: 18490515

101. Watanabe N, Bodin L, Pandey M, Krause M, Coughlin S, Boussiotis VA, Ginsberg MH, Shattil SJ. Mechanisms and consequences of agonist-induced talin recruitment to platelet integrin alphaIIbbeta3. J Cell Biol. 2008 Jun 30; 181(7):1211-22. PMID: 18573917

102. Regard JB, Sato IT, Coughlin SR. Anatomical profiling of G protein-coupled receptor expression. Cell. 2008 Oct 31; 135(3):561-71. PMID: 18984166

103. Li G, Kataoka H, Coughlin SR, Pleasure SJ. Identification of a transient subpial neurogenic zone in the developing dentate gyrus and its regulation by Cxcl12 and reelin signaling. Development. 2009 Jan; 136(2):327-35. PMID: 19103804

104. Hamilton JR, Cornelissen I, Mountford JK, Coughlin SR. Atherosclerosis proceeds independently of thrombin-induced platelet activation in ApoE-/- mice. Atherosclerosis. 2009 Aug; 205(2):427-32. PMID: 19217621


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105. Camerer E, Regard JB, Cornelissen I, Srinivasan Y, Duong DN, Palmer D, Pham TH, Wong JS, Pappu R, Coughlin SR. Sphingosine-1-phosphate in the plasma compartment regulates basal and inflammation-induced vascular leak in mice. J Clin Invest. 2009 Jul; 119(7):1871-9. PMID: 19603543

106. Pham TH, Baluk P, Xu Y, Grigorova I, Bankovich AJ, Pappu R, Coughlin SR, McDonald DM, Schwab SR, Cyster JG. Lymphatic endothelial cell sphingosine kinase activity is required for lymphocyte egress and lymphatic patterning. J Exp Med. 2010 Jan 18; 207(1):17-27. PMID: 20026661

107. Camerer E, Barker A, Duong DN, Ganesan R, Kataoka H, Cornelissen I, Darragh MR, Hussain A, Zheng YW, Srinivasan Y, Brown C, Xu SM, Regard JB, Lin CY, Craik CS, Kirchhofer D, Coughlin SR. Local protease signaling contributes to neural tube closure in the mouse embryo. Dev Cell. 2010 Jan 19; 18(1):25-38. PMID: 20152175

108. Cornelissen I, Palmer D, David T, Wilsbacher L, Concengco C, Conley P, Pandey A, Coughlin SR. Roles and interactions among protease-activated receptors and P2ry12 in hemostasis and thrombosis. Proc Natl Acad Sci U S A. 2010 Oct 26; 107(43):18605-10. PMID: 20930120

109. Green JA, Suzuki K, Cho B, Willison LD, Palmer D, Allen CD, Schmidt TH, Xu Y, Proia RL, Coughlin SR, Cyster JG. The sphingosine 1-phosphate receptor S1P2 maintains the homeostasis of germinal center B cells and promotes niche confinement. Nat Immunol. 2011 Jul; 12(7):672-80. PMID: 21642988

110. Shao B, Wahrenbrock MG, Yao L, David T, Coughlin SR, Xia L, Varki A, McEver RP. Carcinoma mucins trigger reciprocal activation of platelets and neutrophils in a murine model of Trousseau syndrome. Blood. 2011 Oct 13; 118(15):4015-23. PMID: 21860019

111. Arnon TI, Xu Y, Lo C, Pham T, An J, Coughlin S, Dorn GW, Cyster JG. GRK2-dependent S1PR1 desensitization is required for lymphocytes to overcome their attraction to blood. Science. 2011 Sep 30; 333(6051):1898-903. PMID: 21960637

112. Regard JB, Cherman N, Palmer D, Kuznetsov SA, Celi FS, Guettier JM, Chen M, Bhattacharyya N, Wess J, Coughlin SR, Weinstein LS, Collins MT, Robey PG, Yang Y. Wnt/ß-catenin signaling is differentially regulated by Ga proteins and contributes to fibrous dysplasia. Proc Natl Acad Sci U S A. 2011 Dec 13; 108(50):20101-6. PMID: 22106277

113. Yang H, Kim A, David T, Palmer D, Jin T, Tien J, Huang F, Cheng T, Coughlin SR, Jan YN, Jan LY. TMEM16F forms a Ca2+-activated cation channel required for lipid scrambling in platelets during blood coagulation. Cell. 2012 Sep 28; 151(1):111-22. PMID: 23021219

114. Khoufache K, Berri F, Nacken W, Vogel AB, Delenne M, Camerer E, Coughlin SR, Carmeliet P, Lina B, Rimmelzwaan GF, Planz O, Ludwig S, Riteau B. PAR1 contributes to influenza A virus pathogenicity in mice. J Clin Invest. 2013 Jan 2; 123(1):206-14. PMID: 23202729

115. Zhang C, Srinivasan Y, Arlow DH, Fung JJ, Palmer D, Zheng Y, Green HF, Pandey A, Dror RO, Shaw DE, Weis WI, Coughlin SR*, Kobilka BK*. High-resolution crystal structure of human protease-activated receptor 1. Nature. 2012 Dec 20; 492(7429):387-92. PMID: 23222541 *co-corresponding

116. Miller CN, Hartigan-O'Connor DJ, Lee MS, Laidlaw G, Cornelissen IP, Matloubian M, Coughlin SR, McDonald DM, McCune JM. IL-7 production in murine lymphatic endothelial


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cells and induction in the setting of peripheral lymphopenia. Int Immunol. 2013 Aug; 25(8):471-83. PMID: 23657000

117. Herzog BH, Fu Jianxin, Wilson SJ, Hess PR, Sen A, McDaniel JM, Pan Y, Sheng M, Yago T, Silasi-Mansat R, McGee S, May F, Nieswandt B, Morris, AJ, Lupu F, Coughlin SR, McEver RP, Chen H, Kahn ML, Xia L. Podoplanin maintains high endothelial venule integrity by interacting with platelet CLEC-2. Nature. 2013 Oct 3: 502(7469)105-9. PMID: 23995678

118. Bynagari-Settipalli YS, Cornelissen I, Palmer D, Duong D, Concengco C, Ware J, Coughlin SR. Redundancy and interaction of thrombin- and collagen-mediated platelet activation in tail bleeding and carotid thrombosis in mice. Arterioscler Thromb Vasc Biol. 2014 Dec; 34(12):2563-9. PMID: 25278288.

119. Edelstein LC, Simon LM, Lindsay CR, Kong X, Teruel-Montoya R, Tourdot BE, Chen ES, Ma L, Coughlin S, Nieman M, Holinstat M, Shaw CA, Bray PF. Common variants in the human platelet PAR4 thrombin receptor alter platelet function and differ by race. Blood. 2014 Nov 27; 124(23):3450-8. PMID: 25293779.

120. Clay H, Coughlin SR. Mechanical vessel injury in zebrafish embryos. J Vis Exp. 2015; (96). PMID: 25742284.

121. Alsteens D, Pfreundschuh M, Zhang C, Spoerri PM, Coughlin SR, Kobilka BK, Müller DJ. Imaging G protein-coupled receptors while quantifying their ligand-binding free-energy landscape. Nat Methods. 2015 Sep; 12(9):845-51. PMID: 26167642

122. Berger M, Scheel DW, Macias H, Miyatsuka T, Kim H, Hoang P, Ku GM, Honig G, Liou A, Tang Y, Regard JB, Sharifnia P, Yu L, Wang J, Coughlin SR, Conklin BR, Deneris ES, Tecott LH, German MS. Gai/o-coupled receptor signaling restricts pancreatic ß-cell expansion. Proc Natl Acad Sci U S A. 2015 Mar 3; 112(9):2888-93. PMID: 25695968.

123. Prasad JM, Gorkun OV, Raghu H, Thornton S, Mullins ES, Palumbo JS, Ko YP, Höök M, David T, Coughlin SR, Degen JL, Flick MJ. Mice expressing a mutant form of fibrinogen that cannot support fibrin formation exhibit compromised antimicrobial host defense. Blood. 2015 Oct 22; 126(17):2047-58. PMID: 26228483.

124. Wilsbacher LD, Coughlin SR. Analysis of Cardiomyocyte Development using Immunofluorescence in Embryonic Mouse Heart. J Vis Exp. 2015; (97). PMID: 25866997.

125. Page MJ, Lourenço AL, David T, LeBeau AM, Cattaruzza F, Castro HC, VanBrocklin HF, Coughlin SR, Craik CS. Non-invasive imaging and cellular tracking of pulmonary emboli by near-infrared fluorescence and positron-emission tomography. Nat Commun. 2015; 6:8448. PMID: 26423607.

126. Zou J, Tran D, Baalbaki M, Tang LF, Poon A, Pelonero A, Titus EW, Yuan C, Shi C, Patchava S, Halper E, Garg J, Movsesyan I, Yin C, Wu R, Wilsbacher LD, Liu J, Hager RL, Coughlin SR, Jinek M, Pullinger CR, Kane JP, Hart DO, Kwok PY, Deo RC. An internal promoter underlies the difference in disease severity between N- and C-terminal truncation mutations of Titin in zebrafish. Elife. 2015; 4. PMID: 26473617

127. Pfreundschuh M, Alsteens D, Wieneke R, Zhang C, Coughlin SR, Tampé R, Kobilka BK, Müller DJ. Identifying and quantifying two ligand-binding sites while imaging native human membrane receptors by AFM. Nat Commun. 2015; 6:8857. PMID: 26561004.

128. Orr N, Arnaout R, Gula LJ, Spears DA, Leong-Sit P, Li Q, Tarhuni W, Reischauer S, Chauhan VS, Borkovich M, Uppal S, Adler A, Coughlin SR, Stainier DY, Gollob MH. A


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mutation in the atrial-specific myosin light chain gene (MYL4) causes familial atrial fibrillation. Nat Commun. 2016; 7:11303. PMID: 27066836.

129. Clay H, Wilsbacher LD, Wilson SJ, Duong DN, McDonald M, Lam I, Park KE, Chun J, Coughlin SR. Sphingosine 1-phosphate receptor-1 in cardiomyocytes is required for normal cardiac development. Dev Biol. 2016 Jun 19. pii: S0012-1606(15)30086-5. doi: 10.1016/j.ydbio.2016.06.024. [Epub ahead of print] PMID: 27333774

130. To T-L, Schepis A, Ruiz-Gonzalez R, Zhang Q, Yu D, Dong Z, Coughlin SR, Xhu X. Rational design of a GFP-based fluorogenic caspase reporter for imaging apoptosis in vivo. Cell Chemical Biology 2016 23(7):875-82 PMID: 27447051

131. David T, Kim YC, Ely L, Rondon I, Gao H, O'Brien P, Bolt MW, Coyle AJ, Garcia JL, Flounders EA, Mikita T, and Coughlin SR. Factor XIa-specific IgG and a reversal agent to probe FXI function in thrombosis and hemostasis. Science Translational Medicine 2016; 8(252):353ra112 PMID 27559095.

132. 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-Noe 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; Aug 31 Epub ahead of print PMID: 27582371

133. Lefrançais E, Ortiz-Muñoz G, Caudrillier A, Mallavia B, Liu F, Sayah DM, Thornton EE, Headley MB, David T, Coughlin SR, Krummel MF, Leavitt AD, Passegué E, Looney MR. The lung is a site of platelet biogenesis and a reservoir for haematopoietic progenitors. Nature. 2017 Apr 6;544(7648):105-109. doi: 10.1038/nature21706. Epub 2017 Mar 22. PMID: 28329764

134. Ely LK, Lolicato M, David T, Lowe K, Kim YC, Samuel D, Bessette P, Garcia JL, Mikita T, Minor DL, Coughlin SR. Structural Basis for Activity and Specificity of an Anticoagulant Anti-FXIa Monoclonal Antibody and a Reversal Agent. Structure. 2018 Jan 02. PMID: 29336885. PMCID: PMC5803430

135. Zhang Q, Huang H, Zhang L, Wu R, Chung CI, Zhang SQ, Torra J, Schepis A, Coughlin SR, Kornberg TB, Shu X. Visualizing Dynamics of Cell Signaling InVivo with a Phase Separation-Based Kinase Reporter. Mol Cell. 2018 Jan 18; 69(2):334-346.e4. PMID: 29307513. PMCID: PMC5788022

136. Schepis A, Barker A, Srinivasan Y, Balouch E, Zheng Y, Lam I, Clay H, Hsiao CD, Coughlin SR. Protease signaling regulates apical cell extrusion, cell contacts, and proliferation in epithelia. J Cell Biol. 2018 Mar 05; 217(3):1097-1112. PMID: 29301867. PMCID: PMC5839797

137. Jiang X, Wooderchak-Donahue WL, McDonald J, Ghatpande P, Baalbaki M, Sandoval M, Hart D, Clay H, Coughlin S, Lagna G, Bayrak-Toydemir P, Hata A. Inactivating mutations in Drosha mediate vascular abnormalities similar to hereditary hemorrhagic telangiectasia. Sci Signal. 2018 Jan 16; 11(513). PMID: 29339534. PMCID: PMC5811261

138. Zhang Q, Huang H, Zhang L, Wu R, Chung CI, Zhang SQ, Torra J, Schepis A, Coughlin SR, Kornberg TB, Shu X. Visualizing Dynamics of Cell Signaling InVivo with a Phase Separation-Based Kinase Reporter. Mol Cell. 2018 Jan 18; 69(2):347. PMID: 29351851


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139. Zhang Q, Zheng YW, Coughlin SR, Shu X. A rapid fluorogenic GPCR-ß-arrestin interaction assay. Protein Sci. 2018 Apr; 27(4):874-879. PMID: 29411438. PMCID: PMC5866937

140. Wu RS, Lam II, Clay H, Duong DN, Deo RC, Coughlin SR. A Rapid Method for Directed Gene Knockout for Screening in G0 Zebrafish. Dev Cell. 2018 Jul 02; 46(1):112-125.e4. PMID: 29974860

141. Bokoch MP, Jo H, Valcourt JR, Srinivasan Y, Pan AC, Capponi S, Grabe M, Dror RO, Shaw DE, DeGrado WF, Coughlin SR. Entry from the lipid bilayer: a possible pathway for inhibition of a peptide G protein-coupled receptor by a lipophilic small molecule. Biochemistry. 2018 Aug 13. PMID: 30102523

NON-PEER REVIEWED PUBLICATIONS 1. Carethers JM, Coughlin S, Diamond B, Erzurum S, Fried LP, Jameson JL, Kaushansky K,

Klotman ME, Lemon S, Mitchell B, Rothman P, Sawyers C, Seidman C, Somlo S. J Clin. Invest. 2014; 124(9):3680-1. PMCID: PMC4151225

REVIEW ARTICLES 1. Moskowitz, M.A. and Coughlin, S.R. Basic properties of prostaglandins. Stroke 1981 l2:

696‑70l.

2. Moskowitz, M.A. and Coughlin, S.R. Clinical applications of prostaglandins and their inhibitors. Stroke 1981 l2: 882‑886.

3. Williams, L.T., Escobedo, J.A., Keating, M.T., and Coughlin, S.R. The stimulation of paracrine and autocrine mitogenic pathways by the platelet‑derived growth factor receptor. J. Cell Physiol. 1987 Suppl. 5:27‑30.

4. Coughlin SR, Escobedo JA, Williams LT. Molecular mechanisms of platelet-derived growth factor action. Prog Clin Biol Res. 1988. 266:39-45. PMID: 2837788

5. Williams, L.T., Escobedo, J.A., Keating, M.T. and Coughlin, S.R. Signal transduction by the platelet‑derived growth factor receptor. Cold Spring Harbor Symposium on Quantitative Biology 1988. 53: 455‑465.

6. Coughlin, S.R., Vu, T.-K.H., Hung, D.T., and Wheaton, V.I. Perspectives. Characterization of the cloned platelet thrombin receptor: issues and opportunities. J. Clin. Invest. 1992. 89:351-355.

7. Coughlin, S.R., Vu, T.-K.H., Hung, D.T., and Wheaton, V.I. Expression cloning and characterization of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation. Seminars in Thrombosis and Hemostasis 1992. 18(2):161-166.

8. Coughlin, S.R., Scarborough, R.M., Vu, T.-K.H., and Hung, D.T. Thrombin receptor structure and function. Cold Spring Harbor Symposium on Quantitative Biology. The Cell Surface. 1993. 57: 149-154.

9. Coughlin, S.R. Thrombin receptor structure and function. Thrombosis and Haemostasis. 1993. 70(1): 184-187.

10. Coughlin, S.R. Thrombin receptor and cardiovascular disease. Trends in Cardiovascular Medicine 1994. 4(2):77-83.


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11. Coughlin, S.R. Molecular mechanisms of thrombin signaling. Seminars in Hematology. 1994. 31(4) 270-277.

12. Coughlin, S.R. Expanding horizons for G protein-coupled receptors: diversity and disease. 1994. Current Opinions in Cell Biology. 6(2): 191-197.

13. Coughlin, S.R. Protease activated receptors start a family. Proc. Natl. Acad. Sci. USA 1994. 91: 9200-9202.

14. Wilcox, J.N., Nelken, N.A., Coughlin, S.R., and Schall, T.H. Local expression of inflammatory cytokines in human atherosclerotic plaques. J. Athero. and Thrombos. 1994. Vol 1 (Suppl. 1): S10-S13.

15. Coughlin, S.R. How proteases talk to cells---Thrombin receptor recognition and activation. Proc. Alfred Benzon Symposium. Royal Danish Academy of Sciences. 1995.

16. Coughlin, S.R. How thrombin talks to cells: molecular mechanisms and roles in vivo (1997 Sol Sherry Lecture) Arteriosclerosis, Thrombosis, and Vascular Biology 1998. 18(4):514-518.

17. Coughlin, S.R. Protease-activated receptors and platelet function. Thrombosis and Haemostasis 1999. 82:353-356.

18. Coughlin, S.R. How the protease thrombin talks to cells. Proc. Natl. Acad. Sci. USA 1999. 96(20):11023-27.

19. Coughlin, S.R. Thrombin signaling and protease-activated receptors. Nature 2000. 407:258-264.

20. Coughlin, S.R. Protease-activated receptors in vascular biology. Thrombosis and Haemostasis 2001. 86:298-307.

21. Gilman, A.G. et al. Overview of the Alliance for Cellular Signaling. Nature 420(6916):703-6.

22. Coughlin, S.R. Protease-activated receptors in the cardiovascular system. 67th Cold Spring Harbor Symposium on Quantitative Biology 2002. 67:197-208.

23. Coughlin, S.R. PARticipation in inflammation. J. Clin. Invest. 2003. 111:25-7

24. Camerer, E. and Coughlin, S.R. Tickling PAR1: A role in APC signaling and barrier protection? Blood 2005. 105(8): 3004-5.

25. Coughlin, S.R. Protease-activated receptors in hemostasis, thrombosis, and vascular biology. State of the Art Chapter. J. Thromb. Haemost. 2005. 3(8):1800-14.

26. Eagle KA, Ginsburg GS, Musunuru K, Aird WC, Balalban RS, Bennett SK, Blumenthal RS, Coughlin SR, Davidson KW, Frolich ED, Greenland P, Jarvik GP, Libby P, Pepine CJ, Ruskin JN, Stillman AE, Van Eyk JE, Tolunay HE, McDonald CL, Smith SC Jr. Identifying patients at high risk of a cardiovascular event in the near future: current status and future directions: Report of NHLBI working group. Circulation 2010. 121(12): 1447-54.

27. Carethers JM, Coughlin S, Diamond B, Erzurum S, Fried LP, Jameson JL, Kaushansky K, Klotman ME, Lemon S, Mitchell B, Rothman P, Sawyers C, Seidman C, Somlo S. The imperative to invest in science has never been greater. J Clin Invest. 2014 Sep 2; 124(9):3680-1.


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BOOKS AND CHAPTERS

1. Coughlin, S. (1981) Regulation of Vascular Prostacyclin Synthesis, Ph.D. Thesis, Massachusetts Institute of Technology.

2. Coughlin, S. and Williams, L.T. (1984) Antithrombotic therapy and the acute ischemic syndromes. In Acute Coronary Care, (Califf, R. and Wagner, G., Eds.) Boston, Martinus Nijhoff Publishing, pp 135‑144.

3. Williams, L., Tremble, P., Daniel, T., Coughlin, S., Giels, G., and Wang, J. (1985) Platelet‑derived growth factor receptors in normal and transformed cells. In Cold Spring Harbor Symposium on Cancer Cells: Growth Factors and Transformation, (Feramisco, J., Ozanne, B. and Stiles, C., Eds.), New York: Cold Spring Harbor Press, pp 175‑182.

4. Kiwak, K.J., Coughlin, S.R., and Moskowitz, M.A. (1986) Arachidonic acid metabolism in brain blood vessels: implication for the pathogenesis and treatment of cerebrovascular diseases. In Stroke, Pathophysiology, Diagnosis, and Management (Barnett, H., Stein, B., Mohr, J., And Yatsu, F. Eds.) New York: Churchill‑Livingston, pp 141‑164.

5. Williams, L.T., Daniel, T.O., Escobedo, J.A., Fried, V.A., and Coughlin, S.R. (1986) PDGF Receptors: Structural and functional studies. In Advances in Gene Technology: Molecular Biology of the Endocrine System (Puett, D., Ahmad, F., Black, S., Lopez. D., Melner, M., Scott, W., And Whelan, W., Eds.) New York: Cambridge University Press, pp 168‑171.

6. Williams, L.T., and Coughlin, S.R. (1986) Cardiovascular growth factors. In Handbook of Experimental Cardiology (Fozzard, H.M., Haber, E., Jennings, R., Katz,

7. Williams, L.T., Escobedo, J.A., Coughlin, S.R., and Keating, M.T. Expression and function of the PDGF receptor in normal and transformed cells. In Growth Factors and Cancer (M.E. Lippman, editor), in press.

8. Williams, L.T., Coughlin, S.R., Escobedo, J.A., Starksen, N.F., and Keating, M.T., (1988) The expression of genes involved in the mitogenic response to platelet‑derived growth factor. In Mechanisms of Control of Gene Expression, (B. Cullen, L.T. Gage, M.A.Q. Siddiqui, A.M. Skalka, and H. Weissbach, editors), 67:351‑358.

9. Coughlin, S., Escobedo, J., and Williams, L.T. (1988) Molecular mechanisms of platelet‑derived growth factor action. In Second International Symposium on Tissue Repair (Barbul, A., Pines, E., Caldwell, M., and Hunt, T.K., Eds.) New York, Allan R. Liss, Inc. pp 39‑45.

10. Coughlin, S.R., and Keating, M.T. (1989) The platelet‑derived growth factor system. In Oncogenes (Benz, C. and Liu, E., Eds.) Kluwer Academic Publishers, Norwell, MA. pp 169-176.


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11. Coughlin, S.R., (1991) Thrombosis and vascular biology. In: Cardiology (Parmley, W. W. and Chatterjee, K., Eds.) J. B. Lippincott, NY; Vol. 1, Ch. 6. pp 1-10.

12. Coughlin, S.R. (1997) The platelet thrombin receptor. In: The Platelet (Lapetina, E.G., Ed.) JAI Press, Greenwich, CT pp129-143.

13. Coughlin, S.R. (1995) The platelet thrombin receptor. In: Molecular Biology of Thrombosis and Hemostasis. (Roberts, H.R., and High, K.A., Eds.) Marcel Dekker, Inc., NY. pp 639-649.

14. Cantley, L.C. and Coughlin, S.R., Editors (1997) Current Opinion in Cell Biology. Vol. 9, No. 2. Cell Regulation.

15. Coughlin, S.R. (2003) Protease-activated receptors. In: Handbook of Cell Signaling. Bradshaw R. and Dennis E., Editors. Elsevier.

16. Coughlin, S.R., Camerer, E., and Hamilton, J.R. (2005) Protease-activated receptors in hemostasis, thrombosis and vascular biology. In: Hemostasis and Thrombosis, Basic Principles and Clinical Practice. Lippinncott. Eds. Colman R. et al.

SIGNIFICANT PUBLICATIONS 1. Vu TK, Hung DT, Wheaton VI, Coughlin SR. Molecular cloning of a functional thrombin

receptor reveals a novel proteolytic mechanism of receptor activation. Cell. 1991 Mar 22; 64(6):1057-68. PMID: 1672265

Identified the first protease-activated receptor, PAR1, and the molecular mechanism by which the protease thrombin activates platelets and other cells. Initiated the project, designed the experiments, did much of the laboratory work, interpreted the data, wrote the paper.

2. Vu TK, Wheaton VI, Hung DT, Charo I, Coughlin SR. Domains specifying thrombin-receptor interaction. Nature. 1991 Oct 17; 353(6345):674-7. PMID: 1717851

Confirmed the proteolytic activation mechanism put forward in #1. Initiated the project, designed the experiments, did much of the laboratory work, interpreted the data, wrote the paper.

3. Kahn ML, Zheng YW, Huang W, Bigornia V, Zeng D, Moff S, Farese RV, Tam C, Coughlin SR. A dual thrombin receptor system for platelet activation. Nature. 1998 Aug 13; 394(6694):690-4. PMID: 9716134

Identified PAR3 and PAR4, the two remaining thrombin receptors in the mammalian genome. Initiated and guided project, designed experiments with Dr. Kahn, interpreted data, wrote paper.

4. Trejo J, Hammes SR, Coughlin SR. Termination of signaling by protease-activated receptor-1 is linked to lysosomal sorting. Proc Natl Acad Sci U S A. 1998 Nov 10; 95(23):13698-702. PMID: 9811863

With other studies from the lab, this paper answered the question of how signaling by an irreversibly activated receptor is terminated. Initiated and guided project, designed experiments with Dr.Trejo, interpreted data, wrote paper.


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5. Kahn ML, Nakanishi-Matsui M, Shapiro MJ, Ishihara H, Coughlin SR. Protease-activated receptors 1 and 4 mediate activation of human platelets by thrombin. J Clin Invest. 1999 Mar; 103(6):879-87. PMID: 10079109

This paper established that PAR1 and PAR4 together account for activation by thrombin and their relative roles. It was important for stimulating and sustaining interest in PAR1 as a possible target for antithrombotic therapy. Initiated and guided project, designed experiments with Dr. Kahn, interpreted data, wrote paper.

6. Griffin CT, Srinivasan Y, Zheng YW, Huang W, Coughlin SR. A role for thrombin receptor signaling in endothelial cells during embryonic development. Science. 2001 Aug 31; 293(5535):1666-70. PMID: 11533492

Identified a role for thrombin signaling outside the context of response to injury. Specifically, PAR1 function in endothelial cells appears to be necessary for hemostasis and vascular integrity during embryonic development. Initiated and guided project, designed experiments with Ms. Griffin, interpreted data, wrote paper.

7. Sambrano GR, Weiss EJ, Zheng YW, Huang W, Coughlin SR. Role of thrombin signalling in platelets in haemostasis and thrombosis. Nature. 2001 Sep 6; 413(6851):74-8. PMID: 11544528

Established a necessary role for PARs in platelet activation by thrombin by use of knockout mice. Initiated and guided project, designed experiments with Dr.Sambrano, interpreted data, wrote paper.

8. Camerer E, Duong DN, Hamilton JR, Coughlin SR. Combined deficiency of protease-activated receptor-4 and fibrinogen recapitulates the hemostatic defect but not the embryonic lethality of prothrombin deficiency. Blood. 2004 Jan 1; 103(1):152-4. PMID: 14504091

Revealed that, together, platelet activation via PARs and fibrin formation account for the importance of thrombin for hemostasis in vivo. Initiated and guided project, designed experiments with Dr. Camerer, interpreted data, wrote paper.

9. Pappu R*, Schwab SR*, Cornelissen I, Pereira JP, Regard JB, Xu Y, Camerer E, Zheng YW, Huang Y, Cyster JG**, Coughlin SR**. Promotion of lymphocyte egress into blood and lymph by distinct sources of sphingosine-1-phosphate. Science. 2007 Apr 13; 316(5822):295-8. PMID: 17363629 *co-first; **co-corresponding

This paper represented a new direction for the lab. Intrigued by the high levels of S1P1, the GPCR for sphingosine-1-phosphate (S1P), in endothelial cells and the high level of S1P in plasma, we set out to identify the sources and importance of plasma S1P. This paper reports that is supplied to plasma mainly by hematopoietic cells but is supplied to lymph by a different cell type (which we later found to be lymphatic endothelium). Other data confirmed that S1P is indeed very low in the interstitium and that this gradient permits S1P in lymph to function as an exit signal necessary for egress of lymphocytes from lymph nodes into lymph and lymphoid organs into blood. Initiated the project, and designed experiments, interpreted the data and wrote paper with Drs. Pappu, Schwab and Cyster.


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10. Regard JB, Sato IT, Coughlin SR. Anatomical profiling of G protein-coupled receptor expression. Cell. 2008 Oct 31; 135(3):561-71. PMID: 18984166

This paper provided a valuable resource for investigators seeking to use mouse models to probe GPCR function. Initiated and guided project, and designed experiments, interpreted data, wrote paper with Dr. Regard.

11. Camerer E, Regard JB, Cornelissen I, Srinivasan Y, Duong DN, Palmer D, Pham TH, Wong JS, Pappu R, Coughlin SR. Sphingosine-1-phosphate in the plasma compartment regulates basal and inflammation-induced vascular leak in mice. J Clin Invest. 2009 Jul; 119(7):1871-9. PMID: 19603543

Demonstrated a critical role for plasma S1P in maintaining vascular integrity and regulating responses to leak inducing agents in the adult. Initiated and guided project, and designed experiments, interpreted data, wrote paper with Dr. Camerer.

12. Camerer E, Barker A, Duong DN, Ganesan R, Kataoka H, Cornelissen I, Darragh MR, Hussain A, Zheng YW, Srinivasan Y, Brown C, Xu SM, Regard JB, Lin CY, Craik CS, Kirchhofer D, Coughlin SR. Local protease signaling contributes to neural tube closure in the mouse embryo. Dev Cell. 2010 Jan 19; 18(1):25-38. PMID: 20152175

This study revealed an unexpected role for PARs in neural tube closure in the mouse and, more broadly, an unexpected role in regulating epithelial behaviors. It also pointed to PAR2 as a possible physiological substrate for the membrane-tethered protease matriptase, suggesting a local protease-receptor network may regulate epithelial cell behavior. Initiated and guided project, and designed experiments, interpreted data, wrote paper with Dr.Camerer.

13. Zhang C, Srinivasan Y, Arlow DH, Fung JJ, Palmer D, Zheng Y, Green HF, Pandey A, Dror RO, Shaw DE, Weis WI, Coughlin SR*, Kobilka BK*. High-resolution crystal structure of human protease-activated receptor 1. Nature. 2012 Dec 20; 492(7429):387-92. PMID: 23222541 *co-corresponding

The first PAR structure. This off state structure of PAR1 in complex with the drug vorapaxar explained how this drug functions as an irreversible PAR1 antagonist and suggested unusual mechanisms of drug entry and specificity. The structure also revealed substantial differences between PAR1 and previously crystallized GPCRs; these differences suggest that different classes of GPCRs may use different molecular mechanisms to stabilize their off state and to transmit conformational changes across the membrane. The structure also provided know-how that positions us to obtain an on-state structure to identify in detail how the PAR1 tethered ligand activates the receptor and how PAR1 can couple to G1, Gq and G12. This was a team effort between the Coughlin and Kobilka labs. I initiated the project and guided it together with Dr. Kobilka. We wrote the paper together.

PATENTS ISSUED OR PENDING 1. multiple patents issued to UC

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CURRICULUM VITAE1990 John J. Sampson Research Award, AHA California Affiliate (highest score for Grant-in-Aid) 1991 Established Investigator Award, American Heart Association 1991