This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Research in the Soslau laboratory has focused primarily on varying aspects of human platelet biochemistry. The anucleated platelet, derived from the normal fragmentation of the megakaryocyte cytoplasm, along with the coagulation cascade plays a central role in hemostasis. Several different physiological agonists induce platelets to aggregate forming a protective clot with the coagulation-induced fibrin at sites of vascular injury. Selected platelet agonists (thrombin) and surface receptors have long been pharmacologic targets for regulating platelet activation and reducing abnormal hemostatic events, thrombosis. We have shown that there are three distinct thrombin receptors on human platelets that could be activated by different physiological forms of thrombin. These different forms of thrombin respond differentially to many clinically employed antithrombotic drugs that had been presumed to inhibit all levels of thrombin-induced platelet aggregation. Understanding how each form of thrombin and their respective thrombin receptors work in the activation of platelets is crucial to fine tuning the clinical regulation of hemostasis and thrombosis. Studies are also being conducted with human, sea turtle and avian blood to define similarities and differences of platelet/coagulation components involved in hemostasis. Where possible, components are analyzed for structure/function and if major similarities or differences are detected genes will be cloned/sequenced. Ultimately we are interested in evolutionary correlations of sequence/structure/function that may give insights into how mutations in selected human hemostatastic components lead to genetic diseases.
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