Jinhua Wu, PhD
Office Phone: 215-728-2867
Alterations in the regulation or expression of integrins have been implicated in many human diseases including inflammatory disorders, cardiovascular diseases, and cancer. In cancer biology, altered expression of integrins has been linked to tumor cell proliferation, metastasis and survival due to their role as adhesion receptors. Hence the integrin signaling pathway has become an appealing target for cancer therapy. Integrins can be activated by extracellular ligand binding in an outside-in manner or by growth factor stimulation through an inside-out pathway. Although antagonistic inhibitors have been shown to reduce early tumor angiogenesis, the inconsistent effect remain major obstacles for anti-cancer drug development. Alternatively, Integrin activities may also be suppressed by blocking the specific interactions of intracellular elements in the inside-out signaling.
The main focus of my lab is to understand the structural basis of intermolecular complexes and intramolecular rearrangements that control integrin-mediated cell adhesion and motility. Understanding the structural details of each signaling event, particularly the protein-protein interactions involved in this pathway, is the key to developing next-generation inhibitors. We aim to elucidate the structural basis of cytosolic inter-molecular complexes and intra-molecular domain rearrangements that modify the integrin activation, to validate these specific interactions revealed in the crystal structures, and to assess their roles in integrin activation in biochemical and physiological contexts. Our lab employes a combination of X-ray crystallography, biochemical and biophysical assays, cell-based functional studies, computer modeling, and organic synthesis to accomplish these goals.