Graduate School: University of Pennsylvania
Primary Appointment: Professor, Molecular Physiology and Biological Physics
Signaling pathways that regulate contractility in smooth muscle tissues and migrating cells in normal and disease states such an coronary artery disease, asthma and hypertension. Structure function studies of the intercalated disk in the heart.
Email Address: email@example.com
Biomedical Sciences Graduate Program(s)
Our goal is to identify and characterize the function of molecules participating in signal transduction pathways that modulate contractility of smooth muscle both in adult tissues and smooth muscle cells that migrate, for example, during embryonic development to form the coronary vessels. Studies are carried out at the molecular, cellular, tissue and animal level in order to define the physiological or pathophysiological function of the signaling molecules under study. A particular focus is on regulation of myosin phosphatase activity through the small GTPase, RhoA and through cGMP kinase pathways which inhibit and activate this phosphatase, respectively. Apart from standard biochemical, molecular biological technologies and mouse models, other approaches include the photolysis of caged nucleotides and signaling molecules to characterize the regulation and the kinetics of the myosin motors responsible for force development, confocal microscopy and state of the art electron optical methods for studies of localization and translocation of signaling molecules as well as the structural aspects of cellular signal transduction. Electron probe X-ray microanalysis and electron energy loss analysis, which provide compositional information at high spatial resolution (5nm) are currently being applied to address the hypothesis that alteration of Ca2+ in the intercalated disk space leads to disruption of cadherins junctions and electrical conduction in the heart. Ultimately, the search for the basis of hypertension, atherosclerosis and other diseases of the vasculature, as well as the source of some arrhythmias in the heart, drive the research.
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