Molecular Mechanisms Underlying Adaptor-Mediated Integrin Signaling in a Species-Specific Manner

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PROJECT SUMMARY/ABSTRACT My laboratory is interested in understanding the molecular mechanisms underlying cell adhesion and motility mediated by integrins and related small GTPases, and applying these findings to the development of new class of inhibitors for potential therapeutic benefits. Integrins are cell adhesion molecules that transduce signals across the plasma membrane in both directions. Thrombotic disorders, cardiovascular diseases, T cell proliferation defects, and many autoimmune diseases have been linked to the misregulation of integrin expression and its activity. The major gaps in the field of integrin and related signaling pathways include inaccurate molecular models of signaling events mediated by the integrin activator, a lack of understanding to the regulation of different integrin species, unknown mechanism underlying the peculiar dual GTPase specificity of their effector protein, and a lack of inhibitors targeting intracellular adaptors. We have obtained substantial preliminary data to bridge this gaps. The main goals of the lab for the next five years are to investigate the signaling mechanisms of the adaptors and integrins, focusing on the connection of isoforms and posttranslational modifications with specific integrin species and related GTPases, and to develop a new class of adaptor protein inhibitors to control integrin functions. The proposed studies include both basic research and translational research, which reflect an ever-expanding scope of the research in our research program. Our vigorous efforts would undoubtedly support us to achieve the overall goal of conquering integrin related diseases by more effective therapeutic interventions.