Proceedings of the National Academy of Sciences of the United States of America

About the PNAS Member Editor
Name Coughlin, Shaun R.
Location Novartis Institutes for Biomedical Research, Inc.
Primary Field Medical Physiology and Metabolism
Secondary Field Medical Genetics, Hematology and Oncology
 Election Citation
Coughlin has made numerous contributions to the study of signaling mechanisms that are important in cardiovascular biology and disease. He explained how thrombin and other proteases regulate platelets Coughlin showed that protease-activated receptors play unanticipated roles in inflammation and blood vessel development.
 Research Interests
As a cell biologist and cardiologist, I have studied signaling mechanisms that are important in cardiovascular biology and disease. Thrombin, a coagulation protease that is generated at sites of vascular injury, is perhaps the most potent activator of blood platelets, the cells that clump together to prevent bleeding from damaged blood vessels. Thrombin and platelets play a central role in thrombosis, the process that causes most heart attacks and strokes. My laboratory initially focused on the question of how a protease like thrombin can act like a hormone to regulate the behavior of platelets and other cells. We found that thrombin and related proteases can trigger cellular responses via a small family of G protein-coupled protease-activated receptors (PARs). PARs are in essence peptide receptors that carry their own ligands, which remain cryptic until unmasked by proteolytic cleavage of the receptor. Studies of human platelets and PAR knockout mice suggest that PARs are necessary for activation of platelets by thrombin and important in hemostasis and thrombosis. PAR1 may be a rational target for novel drugs aimed at the prevention or treatment of thrombosis. PARs also mediate responses to proteases in endothelial cells and other cell types that may contribute to inflammation and repair after tissue injury. Thus, the coagulation cascade and PARs together provide a mechanism for sensing vascular damage or leak and orchestrating appropriate cellular responses. In an interesting surprise, PARs also appear to play a role in embryonic development in new blood vessel formation and other processes. A current focus of my laboratory is defining the exact role of PARs and the G protein signaling pathways they activate in this context.

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