Shaun Coughlin, M.D., Ph.D., left, talks with Dan Roden, M.D., and John Oates, M.D., following last week’s John A. and Meredith S. Oates Lectureship in Clinical Pharmacology. (Photo by Anne Rayner)
Lecturer reminds scientists to expect the unexpected
Nature can surprise even the most seasoned investigator.
Last week at Vanderbilt University Medical Center, Shaun Coughlin, M.D., Ph.D., of the University of California, San Francisco (UCSF), described his group's discovery that protease-activated receptors play an “unexpected” role in development as well as disease.
In 1991, Coughlin's group reported cloning a thrombin receptor, now known as protease-activated receptor-1 (PAR1), through which thrombin, a protease, activates platelets to form clots.
Clot formation over ruptured atherosclerotic plaques “is the mechanism that underlies a subset of heart attacks and strokes,” Coughlin said during the fourth annual John A. and Meredith S. Oates Lectureship in Clinical Pharmacology.
A PAR1 antagonist that blocks thrombin-mediated platelet activation is now in phase III clinical trials for acute coronary syndrome and secondary prevention of heart attack and stroke.
“We'll see,” said Coughlin, director of the Cardiovascular Research Institute and Distinguished Professor of Cardiovascular Biology and Medicine at UCSF. “It'll either be a good story or a lot of money.”
More recently, he said, “we've tripped over roles in embryonic development for (protease-activated receptors).” In particular, PAR1 and PAR4 are involved in the formation of blood vessels, and PAR2 seems to be important in neural tube closure.
The Oates Lectureship, established in 2006, is named for John Oates, M.D., founding director of the Vanderbilt Division of Clinical Pharmacology, and his wife, Meredith. Oates is internationally known for his research on prostaglandins and related molecules.
This year's lecture was hosted by the Division of Clinical Pharmacology.