My colleague and I are interested in structure-function relationship and regulation of ADAMTS13 and ADAMTS7 metalloproteases. We focus on their role in pathogensis of arterial thrombosis and atherosclerosis. ADAMTS13, a plasma metalloprotease, cleaves von Willebrand factor (vWF) and regulates vWF multimer sizes. Deficiency of ADAMTS13 activity leads to thrombotic thrombocytopenic purpura (TTP) and many other arterial thrombotic disorders. My colleague and I are interested in understanding of the pathogenesis of TTP by investigating the structural components of ADAMTS13 protease required for substrate recognition in vitro and in vivo. We are also interested in determining the epitopes anti-ADAMTS13 IgG autoantibodies bind. Finally, we are interested in identifying novel protein or non-protein cofactors that accelerate ADAMTS13 enzymatic function and in developing viral vector and cell-based molecular therapies for treatment of TTP and related disorders. ADAMTS7, a closely related metalloprotease to ADAMTS13, cleaves cartilage oligomeric matrix protein (COMP). It has recently been identified as a risk factor for atherosclerosis and cardiovascular diseases. Little is known about the biochemistry and physiological functions of ADAMTS7 in atherosclerosis and thrombosis. My colleague and I are interested in understanding of the structure-function relationship of ADAMTS7 in recognition of novel substrates. In addition, we are interested in developing novel fluorescein-labeled peptide assays for assessing plasma ADAMTS7 activity in patients with various cardiovascular diseases. The advances in these areas will not only shed more light on the pathogenesis of TTP and atherosclerosis, but also provide tools for diagnosis and treatment of TTP and many other arterial thrombotic disorders including myocardial infarction and ischemic stroke.