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Our long-term interest is to have a better understanding of the natural antithrombotic pathways and the pathophysiology of vascular thrombosis. We have focused on thrombin, the key enzyme in the blood clotting cascade. Using a library of thrombin mutants generated by site-directed mutagenesis, we have mapped the critical functional sites on thrombin for its interactions with its diverse substrates. We are studying a thrombin-activatable carboxypeptidase that plays a key role in the physiologic regulation of thrombin's pro-thrombotic and pro-inflammatory properties. Our goal is to develop new antithrombotic agents and devise new diagnostic tests for vascular thrombotic disorders.