University of Virginia Health System

Regulation of cell behavior by adhesion to extracellular matrix (ECM) is a fundamental fact of multicellular life. Virtually every cell in vertebrates spends at least a portion of its life cycle adhered to ECM, and this interaction critically regulates cell survival, growth, gene expression and function. Integrins are the major membrane receptors that mediate adhesion of cells to ECM. In doing so they connect the actin cytoskeleton inside the cell to the ECM to provide mechanical integrity. My lab is among those that, in the late 1980’s, showed that integrins also transduce signals. These signals are complex and varied, and appear to mediate many if not most of the regulatory effects of ECM. My laboratory's overall goal is to understand how integrins signal, how these signals regulate cell functions, and how they fit into the larger picture of cell regulation by soluble factors, oncogenes, and mechanical forces. A major area of current research involves elucidating basic mechanisms of integrin signaling, including the connections between integrins and Rho family GTPases and c-Abl tyrosine kinase. This work includes developing and using new fluorescence-based assays to visualize activation of signaling molecules in living cells. We are also studying how integrins and Rho family GTPases participate in mechanotransduction. The lab also has two applied projects relevant to developing new cancer therapies. We are studying endothelial cell migration with the goal of developing anti-angiogenic therapies. We are also studying how integrins modulate the response of cells to DNA damage with the goal of improving chemo and radiation therapy.