Glenn I. Fishman, MD

My laboratory focuses on several facets of cardiovascular biology and disease. First, we are interested in the formation and function of the heart's specialized cardiac conduction system (CCS). This complex network comprises pacemaking cells that establish the normal rhythmicity of the heart, as well as rapidly conducting His-Purkinje cells that facilitate highly synchronized excitation of the working myocardium.

Our studies of the conduction system utilize genetically engineered mouse models that specifically visualize various components of the network. Gene profiling of microdissected CCS tissue is then employed to identify the molecular signature of these specialized cells. A complementary approach for gene discovery using murine embryonic stem cells is being developed, whereby such pluripotent cells can be differentiated into specific components of the CCS under defined cultured conditions.

A second area of investigation includes studies of arrhythmia mechanisms, focusing especially on the dysregulation of gap junction channels and the associated abnormalities in impulse propagation. These studies include a multiple of strategies that range from molecular and biochemical through genetically engineered murine models with site-specific mutations in connexin genes, which encode the gap junction channel proteins. Our laboratory was the first to demonstrate the essential role of gap junction channels in cardiac rhythmicity, using conditional knockout approaches. Current studies are focused on defining the role of post-translational regulation of connexins during normal gap junction formation and in response to pathologic stimuli that lead to abnormal gap junction remodeling.