Mensing forces through integrins: mechanisms and implications for biology and medicine
Robert W. Berliner Professor of Medicine (Cardiology) and Professor of Biomedical Engineering and of Cell Biology
May 10, 2018
Foege N130A, Wallace H. Coulter Seminar Room
The morphogenesis and physiology of our tissues are highly dependent on mechanical forces applied strains and tissue stiffness. Further, the major pathologies of these organs, including hypertension, atherosclerosis, heart failure and fibrosis involve altered forces and tissue stiffness, or altered cell sensing of these variables. My lab investigates the basic mechanisms by which cells sense matrix stiffness, applied strains and fluid shear stress, and how these sensing mechanisms contribute to cardiovascular disorders. I will present our latest work on elucidation of these mechanotransduction pathways and their role in cardiovascular remodeling and disease.
Prof. Schwartz earned his Ph.D. at Stanford University, where he worked with Harden McConnell on biophysics of model membranes. He then did postdoctoral research with Richard Hynes at MIT, where he studied interactions of fibronectin. As an assistant professor in the Department Physiology and Biophysics at Harvard Medical School, his lab was among the first to demonstrate signaling by integrins and the first to report that integrin-mediated adhesion is required for transmission of signals downstream of growth factor receptors. His lab was the first to show that Rho family GTPases are signaling intermediates on integrin pathways. In the Dept. of Vascular Biology at Scripps, his lab was the first to report that cell adhesion is required for survival of endothelial and other cells. His lab developed the widely used pull down assay for Rho activity and were the first to show that adhesion regulates Rho activity. His work also identified the first bona fide mechanotransducer for fluid shear stress in endothelial cells, elucidated the role of extracellular matrix proteins in shear responses in atherosclerosis and tested these ideas in animal models of atherosclerosis. His lab has also invented and used fluorescence based assays for visualizing signaling events in live cells, including sensors that measure molecular tension across specific proteins. His major goal is to understand the roles of mechanotransduction and integrin signaling in vascular physiology and disease.