The goals of the SCOR in Thrombosis are to elucidate and characterize basic mechanisms and pathways involved in the pathogenesis of thrombosis at the molecular and genetic levels, to characterize normal and abnormal biochemical and cellular activities which arise from the interactions of platelets with the vascular wall, to establish normal and abnormal levels of coagulant/coagulant related proteins, and to develop the means to modify and prevent thrombotic disease and its consequences in man.
The specific aims of this proposal include: a) the elucidation and characterization of receptor/response coupling in thrombin-stimulated platelets and in platelet-derived growth factor (PDGF) stimulated cells, b) the elucidation of receptor coupled pathways in thrombin activated platelets and in PDGF-stimulated vascular cells, c) the analysis of binding sites, sites of interaction with other proteins and function of the platelet secretory protein, thrombospondin and the thrombin inhibitor, heparin co-factor II, d) the characterization of protein Z, for which a physiological role has not yet been described, e) the elucidation of the gene structure, gene regulatory sites, chromosomal locus, and predicted amino acid sequence of four proteins (thrombospondin, heparin co-factor II, thrombomodulin, tissue factor), f) the elucidation of the role of fibrinopeptides and thrombin in directed migration of vascular cells, and g) the measurement of levels of recently discovered coagulation-associated proteins in normal patient populations and in populations of patients with well-defined diseases, using recently developed radioimmunoassays. The methods to be utilized include: a) protein purifications and characterizations, b) recombinant DNA technology, c) cell biological technology as applied to DNA synthesis, directed cell migration, and cell growth, d) immunological techniques as applied to molecular probing and activity assays. Multiple collaborative investigations both within this SCOR and with other SCOR programs are ongoing and will be developed further. Internal coordination of programs and extensive internal and external review processes are planned; conferences and relevant courses will be used to disseminate results and to interest new investigators in the field of thrombosis. The SCOR program thus plans a highly integrated and highly directed effort to further understanding of thrombotic disease and to develop means for effective diagnosis and therapy.
