Vessel wall injury triggers sudden platelet activation and platelet plug formation, followed by coagulant activity and the formation of fibrin-containing thrombi which occlude the site of injury. These events are crucial to limit blood loss at sites of tissue trauma but may also block diseased vessels leading to ischemia and infarction of vital organs. The major objective of our research is to understand the functional role of platelet membrane glycoproteins and their signaling pathways in normal hemostasis as well as in thrombotic and inflammatory diseases. We use genetically modified mouse strains with defined defects in platelet receptors or signaling molecules to study platelet adhesion and activation processes in vitro and in vivo. These experiments serve as a basis for the development of antibody-based antithrombotic therapies which are then evaluated in murine models of arterial thrombosis and systemic inflammation.