Platelet adhesion to damaged vascular endothelium plays a key role in normal hemostasis, and has been implicated in the formation of the atheromatous plaque and acute thrombosis, leading to coronary artery disease, stroke, and peripheral vascular disease. Since collagen is a potent platelet-activating and aggregating agent and is found in high concentration in the blood vessel wall, there is good reason to believe that the interaction between platelets and collagen plays an important role in both hemostasis and thrombosis. This interaction is thought to involve a specific platelet membrane receptor for collagen, but there is controversy as to its nature. The goals of this proposal are twofold. The first is to provide the applicant with a rigorous and intensive course of study under the guidance of an experienced investigator. This course will encompass all of the theoretical and practical aspects of the preparation, purification and characterization of murine monoclonal antibodies, in addition to formal course work in advanced immunology, biochemistry, and pathology. The second goal is to improve our understanding of the biochemistry and physiology of platelet function through development of murine monoclonal antibodies directed against the platelet receptor for collagen. The antibodies will be used to: 1) identify and characterize the receptor for collagen, 2) quantify the number of binding sites per platelet in normal platelets and those from patients suffering from thrombotic diseases, 3) explore the interactions of Clq and collagen with platelets, and 4) study whether antibodies or antibody fragments directed against the collagen receptor can prevent platelet adhesion to damaged blood vessels. Completion of this project will enhance our understanding of platelet physiology, and will enable the Principal Investigator to develop his skills to the point where he can successfully carry out independent research in accordance with the aims of the Physician-Scientist program.
| Steinberg, M H; Kelton, J G; Coller, B S (1987) Plasma glycocalicin. An aid in the classification of thrombocytopenic disorders. N Engl J Med 317:1037-42 |
