Cell surface proteases contribute to a wide variety of biologic processes involving cell migration, cell differentiation, or matrix remodeling. Endothelial cells, for example, use cell surface proteases to maintain a thromboresistant lining in all blood vessels. They also employ matrix-remodeling proteases to create new blood vessels in response to angiogenic stimuli. Macrophages and tumor cells employ such proteases to migrate and establish themselves at sites of inflammation or metastasis. Developing neuronal cells require protease activity for neuritogenesis.

Work in our laboratory focuses on the receptor-mediated assembly of the fibrinolytic zymogen, plasminogen, and its endothelial cell-derived activator, tissue plasminogen activator. Together, these molecules efficiently generate plasmin, a serine protease with broad substrate specificity. Annexin 2 is a dual ligand receptor that mediates this assembly and promotes plasminogen activation at cell surfaces. Our present studies focus on annexin II in [1] control of hemostasis and thrombosis, [2] macrophage migration and matrix remodeling, [3] neuronal cell differentiation, [4] tumor cell invasion and metastasis, and [5] cardiovascular development and angiogenesis.

These studies involve a wide variety of molecular, biochemical, and in vivo physiologic techniques including expression screening, quantitative PCR, transfection procedures, Northern and Southern hybridization assays, protein purification, analytical electrophoresis and blotting, enzyme kinetic assays, and whole animal models of thrombosis, cardiovascular function, and angiogenesis.

Email: khajjar@med.cornell.edu


Email: khajjar@med.cornell.edu