Shaun R. Coughlin, MD, PhD

Massachusetts Institute of Technology, Boston, MA, S.B., S.B., 1976, Biology, Physics
Massachusetts Institute of Technology, Boston, MA, S.M., 1976, Biochemistry
Massachusetts Institute of Technology, Boston, MA, Ph.D., 1981, Neur. and Endo. Reg.
Harvard Medical School, Boston, MA, M.D., 1982, Medicine

• 1982-1984
  Intern and Resident, Medical Services, Massachusetts General Hospital
• 1984-1985
  Assistant Research Cardiologist, Cardiovascular Research Inst., UCSF
• 1985-1986
  Clinical Fellow in Cardiology, University of California, San Francisco
• 1986-1991
  Assistant Professor of Medicine and Associate Staff, Cardiovascular Research Intitute, UCSF
• 1991-1996
  Associate Professor of Medicine and Senior Staff, Cardiovascular Research Institute, UCSF
• 1992-present
  Member, Graduate Program in Biological Sciences and Program in Biomedical Sciences, UCSF
• 1995-present
  Director, Daiichi Research Center, UCSF
• 1996-present
  Professor of Medicine, UCSF
• 1997-present
  Professor of Cellular and Molecular Pharmacology, UCSF
• 1997-present
  Director, Cardiovascular Research Institute, UCSF

• Established Investigator, AHA; Ted Zimmerman Lecture, ASH, 1991
• 1992
  ASCI
• 1994
  Syntex Prize in Receptor Pharmacology
• 1997
  AAP; Owren Lecture, Oslo; AHA Sol Sherry Lecture
• 1998
  Outstanding Investigator Award, AFMR
• 2000
  Hoeg Award, AHA
• 2000
  Fellow, American Academy of Arts and Sciences
• 2000
  Russel Ross Lecture, AHA
• 2002
  Pasarow Foundation Award for Cardiovascular Research
• 2003
  Basic Science Prize, AHA
• 2004
  14th Bristol-Meyers Squibb Award for Distinguished Achievement in Cardiovascular Research
• 2004
  Member, National Academy of Sciences

• Recent Primary Publications
• Kahn, M.L., Zheng, Y.-W., Huang, W., Bigornia, V., Zeng, D., Moff, S., Farese, R.V., Jr., Tam, C., and Coughlin, S.R. (1998) A two thrombin receptor system for platelet activation. Nature 394: 690-694.
• Kahn, M.L. Hammes, S.R., Botka, C., and Coughlin, S.R. (1998) Gene and locus structure and chromosomal localization of the protease-activated receptor gene family. J. Biol. Chem. 273: 23290-23296.
• Shapiro, M.J. and Coughlin, S.R. (1998) Separate signals for agonist-independent and agonist-triggered trafficking of protease-activated receptor-1. J. Biol. Chem. 273: 29009-29014.
• Trejo, J. and Coughlin, S.R. (1999) The cytoplasmic tails of protease-activated receptor-1 and substance P receptor specify sorting to lysosomes vs. recycling. J. Biol. Chem. 274: 2216-2224.
• Hammes, S.R. and Coughlin, S.R. (1999) 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 38(8): 2486-2493.
• Kahn, M.L., Nakanishi-Matsui, M., Shapiro, M.J., Ishihara, H., and Coughlin, S.R. (1999). Protease-activated receptors 1 and 4 mediate activation of human platelets by thrombin. J. Clin. Invest. 103: 879-887.
• Hammes, S.R. , Shapiro, M.J., and Coughlin, S.R. (1999) Shutoff and agonist-triggered internalization of protease-activated receptor-1 are separable by mutation of putative phosphorylation sites in the cytoplasmic tail. Biochemistry 38: 9308-9316.
• Sambrano, G. and Coughlin, S.R. (1999) The carboxyl tail of protease-activated receptor-1 is required for chemotaxis: correlation of signal termination and directional movement. J. Biol. Chem. 274: 20178-20184.
• Kahn, M.L., Diacovo, T., Bainton, D.F., Lanza, F., Trejo, J., and Coughlin, S.R. (1999) Glycoprotein V-deficient platelets have undiminished thrombin responsiveness and do not exhibit a Bernard-Soulier phenotype. Blood 94: 4112-4121.
• Cunningham, M.A., Rondeau, E., Chen, X., Coughlin, S.R., Holdsworth, S.R., and Tipping, P.G. (2000) Protease-activated receptor-1 mediated, fibrin independent pro-inflammatory actions of thrombin in crescentic glomerulonephritis. J. Exp. Med. 191(3): 455-461..
• Sambrano, G.R., Huang, W., Faruqi, T., Mahrus, T., Craik, C., and Coughlin, S.R. (2000) Protease-activated receptor-4 mediates human platelet activation by cathepsin G. J. Biol. Chem. 275: 6819-6823.
• Nakanishi-Matsui, M., Zheng, Y.-W., Weiss, E.J., Sulciner, D., and Coughlin, S.R. (2000) PAR3 is a cofactor for PAR4 activation by thrombin. Nature 404: 609-613..
• Camerer, E., Huang, W., and Coughlin, S.R. (2000) Tissue factor- and Factor X-dependent activation of PAR2 by Factor VIIa. Proc. Natl. Acad. Sci. USA 97(10): 5255-5260.
• Faruqi, T.R., Weiss, E.J., Huang, W., and Coughlin, S.R. (2000) Structure- function analysis of protease-activated receptor-4 tethered ligand peptides: Determinants of specificity and utility in assays of receptor function. J. Biol. Chem. 275:19728-34.
• Shapiro, M.J., Weiss, E.J., Faruqui, T.R., and Coughlin, S.R. (2000) Protease-activated receptors 1 and 4 are shutoff with distinct tempos after activation by thrombin. J. Biol. Chem. 275:25216-21.
• Takeuchi, T., Harris, J.L., Huang, W., Yan, K.W., Coughlin, S.R., and Craik, C.S. (2000) Cellular localization of MT-SP1 and identification of PAR2 and sc-uPA as substrates. J. Biol. Chem. 275:26333-26342.
• Trejo, J., Alschuler, Y., Fu, H.-W., Mostov, K.E., and Coughlin, S.R. (2000) A Mutant HeLa Cell Line Reveals Distinct Requirements for Recruitment of Protease-Activated Receptor-1 vs. 2-Adrenergic Receptor to Clathrin-Coated Pits. J. Biol. Chem. 275:31255-31265.
• Linder, J.R., Kahn, M.L., Coughlin, S.R., Schauble, E., Bernstein, D., Foy, D., Harezi-Moghadam, A., and Ley, K. (2000) Delayed onset of inflammation in protease-activated receptor 2-deficient mice. J. Immunology 165:6504.
• Sambrano, G., Weiss, E., Zheng, Y.W., Huang, W., and Coughlin, S.R. (2001) Role of thrombin signaling in platelets in hemostasis and thrombosis. Nature 413: 74-78.
• Griffin, C.T., Srinivasan, Y., Zheng, Y.W., Huang, W., and Coughlin, S.R. (2001) A role for thrombin receptor signaling in endothelial cells during embryonic development. Science 293: 1666-1670.
• Camerer, E., Kataoka, H., Zheng, Y.-W., Kahn, M.L., Lease, K., and Coughlin, S.R. (2002) Genetic evidence that protease-activated receptors mediate factor Xa signaling in endothelial cells. J. Biol. Chem. 277:16081-16087.
• Weiss, E.J., Hamilton, J.R., Lease, K.E., and Coughlin, S.R. (2002) Protection against thrombosis in mice lacking PAR3. Blood 100(9):3240-3244.
• Eisenhaure TM, Francis SA, Willison LD, Coughlin SR, Lerner DJ. (2003) 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. 278(33):30975-84.
• Camerer, E., Duong, D.N., Hamilton, J.R., and Coughlin, S.R. (2004) Combined deficiency of protease-activated receptor-4 and fibrinogen recapitulates the hemostatic defect but not the embryonic lethality of prothrombin deficiency. Blood 103(1):152-4.
• Ludeman, M.J., Zheng, Y.W., Ishii, K., and Coughlin, S.R. (2004) Regulated shedding of PAR1 N-terminal exodomain from endothelial cells. J. Biol. Chem. 279:186592-9.
• Camerer, E., Qazi, A.A., Duong, D.N., Cornelissen, I., and Coughlin, S.R. (2004) Platelets, protease-activated receptors and fibrinogen in hematogenous metastasis. Blood (In press).
• Hamilton, J.R., Cornelissen, I., and Coughlin, S.R. (2004) Impaired hemostasis and protection against thrombosis in PAR4-deficient mice is due to lack of thrombin signaling in platelets. J. Thrombos. Haemostas. (In press).
• Selected earlier publications:
• Vu, T.-K.H., Hung, D.H., Wheaton, V.I., and Coughlin, S.R. (1991) Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation. Cell 64:1057-1068
• Connolly, A., Ishihara, H., Kahn, M., Farese, R.V., Jr., and Coughlin, S.R. (1996) Role of the thrombin receptor in development and evidence for a second receptor. Nature 381: 516-519.