Vascular dysfunction in hyperhomocysteinemia
This project originated from studies in this laboratory on prothrombotic effects of elevated levels of homocysteine, an amino acid that is associated with coronary artery disease, stroke, peripheral vascular disease, and venous thrombosis. We were among the first to demonstrate impaired vascular function in moderate hyperhomocysteinemia. Current studies are directed toward investigating the mechanisms of vascular dysfunction in hyperhomocysteinemia and atherosclerosis using molecular genetic approaches. Supported by the Department of Veterans Affairs, the National Institutes of Health, and the American Heart Association.
Structure and function of thrombomodulin
This project originated from our discovery that the anticoagulant protein thrombomodulin is expressed in a highly regulated fashion by keratinocytes in squamous epithelium. Our recent studies suggest that thrombomodulin regulates tissue repair during cutaneous wound healing. Current studies are directed toward investigating the function of thrombomodulin in endothelium and epithelium using gene targeting approaches. Supported by the Department of Veterans Affairs.
Platelet signal transduction by thrombin and collagen
Thrombin is a multifunctional serine protease that acts as a pivotal enzyme in blood coagulation. We have characterized thrombin receptor signal transduction in platelets and T cell lines, and demonstrated counter-regulation between thrombin receptors and the T cell antigen receptor. These observations support the model that thrombin provides a functional link between hemostasis and immune activation. We have demonstrated that the adapter protein SLP-76 ("SH2 domain containing leukocyte phosphoprotein of 76 kD") is essential for platelet signal transduction in response to collagen, but not thrombin. Currently, we are using genetic approaches in mice to define the hemostatic consequences of impaired collagen signal transduction. Supported by the American Heart Association, the Howard Hughes Medical Institute, and the National Institutes of Health.