Research

Our research goal is to understand the mechanisms by which cardiovascular diseases such as atherosclerosis and stroke develop. We are particularly interested in identifying intracellular signaling pathways that cause platelets to change their membrane properties, aggregate, and interact with leukocytes and the blood vessel wall, facilitating the development of atherosclerosis.

We also investigate mechanisms by which endothelial cells are activated, accelerating inflammation, thrombosis, and atherosclerosis. We have shown that GP Ib-IX, a major transmembrane receptor on platelets is phosphorylated by agents such as prostacyclin I2 that are produced by healthy endothelial cells. When phosphorylated, GP Ib-IX binds 14-3-3, preventing it from stimulating intracellular pathways that accelerate platelet activation and aggregation. We are testing the hypothesis that phosphorylation is decreased when platelets are stimulated by the high-shear forces in diseased vessels and by catecholamines, which are elevated under conditions of psychological stress.

We are also studying the signals transmitted across integrins, another transmembrane receptor that is present on both platelets and endothelial cells. One of the enzymes activated by integrins is calpain.

We are studying the way in which calcium causes intracellular signaling leading to increased platelet adhesion and to activation of transcription factors and increased expression of inflammatory proteins in endothelial cells.