CVRI Scientists

Ethan J Weiss, M.D.
Assistant Professor of Medicine

Research Interests:
Genetic regulation of blood clotting in mice; sex differences in blood clotting.

Summary:
The blood clotting system is centrally important as a means to protect from blood loss. To do so, the system must be sensitive to disruptions in blood vessels. We know from naturally occurring human genetic mutations and experiments in animals that a deficiency of function or amount of clotting related proteins leads to bleeding. Yet the system must also be specific. There is an equal body of evidence that unregulated or increased propensity to form blood clots leads to deleterious clot formation such as occurs in heart attacks, strokes, and blood clots in large veins. The clotting system therefore must maintain exquisite balance between tendency toward clotting and tendency toward bleeding. Minor changes in concentration or function of a host of known and countless unknown proteins can tip the balance in either direction. Primarily, we use the mouse as a model system to define genetic regulation of blood clotting in an attempt to define genetic changes that might predispose to tipping the balance in either direction. We hope to learn more about the molecules and pathways that lead to clot formation. We hope to define novel molecules or pathways that regulate clotting or interact with known clotting pathways. We are particularly interested in how male or female sex affects clotting in animals. We know that women are 1) less likely to form clots in clotting tests and 2) are protected as compared to men in diseases associated with increased clotting like heart attacks. This tells us that women may have evolved a system with a more favorable balance between clotting and bleeding. We hope to learn how and why that may be. Ultimately, we hope to identify new risk factors for bleeding disorders as well as the clotting associated diseases such as heart attack and stroke. Furthermore, we hope that by understanding the biological mechanisms underlying such risks, we might eventually identify novel drug targets aimed at treating or preventing bleeding, stroke, heart attack or blood clots.