Research Interests

I am interested in the regulation of blood clotting, especially the role of the blood vessel proteins in controlling clot formation. Tight regulation of the clotting process is essential to stopping blood loss at wound sites and preventing occlusive blood clots (thrombi) from forming. Biochemical and genetic approaches allowed us to identify two proteins on the endothelial blood vessel lining, thrombomodulin and the endothelial cell protein C receptor, that are critical to controlling blood clotting. Thrombomodulin binds thrombin and prevents it from clotting fibrinogen and activating platelets. It also switches the macromolecular specificity of thrombin so that it activates a plasma zymogen, protein C. Activated protein C then stops further thrombin generation by proteolytically inactivating two key coagulation proteins, factors Va and VIIIa. Activated protein C has additional anti-inflammatory properties. The endothelial cell protein C receptor augments protein C activation and appears to be critical for cellular signaling by activated protein C. I am particularly interested in how this system responds to acute inflammatory challenges, and I am working to identify the receptors involved. I am also creating genetically modified mice to explore the mechanisms by which this system modulates vascular injury in a variety of disease processes, including auto-immunity.

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Primary Section

Section 41: Medical Genetics, Hematology, and Oncology