Steven Fisher

Associate Professor

M.D. University of Pennsylvania, 1986
View Curriculum Vitae

Molecular mechanisms of development and differentiation in the cardiovascular system

RESEARCH DESCRIPTION

I use two completely unrelated experimental models in my laboratory. One model concerns the regulation of gene expression in vascular smooth muscle and how this influences vascular function in development and disease. We have proposed that the regulated expression of isoforms of the myosin phosphatase (MP) determines the sensitivity of vascular smooth muscle to NO/cGMP mediated vasorelaxation. More recently we have shown that the expression of vascular smooth muscle MP is dynamically regulated by changes in blood flow and blood pressure. We are currently testing the model of MP isoforms and vascular function using transgenic mouse models. We are also engaged in identifying the cis- and trans-factors that determine the tissue-specific, developmentally regulated and disease modulated expression of MP isoforms.

The second experimental model examines the role of myocardial hypoxia in the remodeling of the embryonic cardiac outflow tract (OFT). We have proposed that tissue hypoxia triggers the programmed cell death-dependent remodeling of the cardiac OFT that drives the resorption of the myocardial portion of the OFT as the embryo makes the transition to a dual series circulation. We are currently focused on identifying the gene targets of the hypoxia-inducible transcription factor (HIF-1) that may mediate the death or survival of cardiomyocytes in the OFT. We are also further defining this pathway of cell death. In these experiments we use recombinant adenovirus to deliver survival or death genes to the heart in ovo, and have recently begun using targeted gene knock-out to test this model.

RELATED RESEARCH AREAS

View Steven Fisher's Publications on PubMed