Research Overview
Control of blood cell reactivity by vascular endothelium
My Thrombosis Research Laboratory has continuously focused on basic and applied research in blood platelet, neutrophil, and erythrocyte biochemistry and molecular biology so as to obtain new insights into the phenomena of blood vessel occlusion, blood coagulation, and host defense mechanisms. Current therapeutic modalities for occlusive vascular diseases represent major advances, but each of them is potentially hazardous and prohibitively expensive. Thus, our efforts have been directed toward development of a new antithrombotic agent which will be devoid of complications, therapeutically effective, and economically viable.
During the 1980's and early 1990's, I initiated my metabolic studies of cell-cell interactions which led to a new discipline known as Transcellular Metabolism. I demonstrated that different cells in proximity could produce metabolic products which neither cell could synthesize alone. This was also the basis of aspirin-sensitive asthma and became the foundation for a new discipline in biochemistry and molecular biology.
Our research is currently focusing on the platelet response to vascular injury. Our in vitro studies have demonstrated that platelets are unresponsive to agonists when in motion and in proximity to endothelial cells. We ascertained that this lack of responsiveness is governed by three separate endothelial cell Thromboregulatory Systems: Eicosanoids (PGI2), Endothelium-Derived Relaxing Factor or Nitric Oxide (EDRF/NO), and an ecto-nucleotidase on the endothelial cell surface.
A major new development is the recognition of sequence homology between the endothelial cell ADPase we have been studying and a lymphoid cell activation antigen, known as CD39. We now feel that these novel research results represent the foundation for development of a therapeutic agent. This agent would be administered to patients with occlusive vascular disorders which have developed in the framework of a low threshold for platelet reactivity.
