The research in this lab has focused on the molecular and cellular mechanisms of blood coagulation, fibrinolysis and atherosclerosis, as analyzed through the use of various biophysical and structural techniques, including visualization of molecules and supramolecular aggregates and measurements of mechanical properties of cellular and extracellular structures. We are investigating the function of various domains of fibrinogen using recombinant fibrinogens and dysfibrinogenemias, as well as conformational changes that occur. Structural studies designed to elucidate the intermolecular interactions in all steps of fibrin clot formation and fibrinolysis are being carried out. Relationships between clot structure and mechanical properties are also an important part of this work. Molecular mechanisms of the dissolution of the clot by the fibrinolytic system are under investigation. The interactions of integrins with various adhesive proteins and with the cytoskeleton is also a focus of research, especially in platelet aggregation and cellular and extracellular matrix interactions in atherosclerosis. The results of these studies have implications for basic mechanisms of protein-protein and protein-cell interactions as well as for clinical aspects of hemostasis, thrombosis and atherosclerosis.