Steven A. Fisher, MD
Year elected: 2005
Current membership category: Senior
ProfessorUniversity of Maryland School of Medicine
S-012c HSF II
20 S. Penn St
Baltimore, MD 21044
United States of America
During his medical training Dr. Fisher became interested in cardiovascular remodeling in development and disease. Dr. Fisher developed two experimental models: 1) By deploying a novel method of gene delivery to the embryonic heart, he showed that cardiomyocyte programmed cell death (PCD) is necessary for the remodeling of the cardiac outflow tract in the transition from a single to a dual series circulation. He demonstrated that perturbations in PCD cause conotruncal heart defects that model congenital human heart defects, including Tetrology of Fallot and Transposition of the Great Arteries. Dr. Fisher has proposed that myocardial hypoxia signaling through HIF-1 transcription is the trigger for PCD-dependent remodeling of the OFT. This provides the first experimental support for the long held belief that the dual series circulation evolved in warm-blooded animals to maximize oxygen delivery to the peripheral tissues, i.e. as a response to tissue hypoxia. It also suggests novel molecular targets for environmental exposures that are associated with human conotruncal heart defects. 2) The second model studies regulated gene expression, smooth muscle phenotypic diversity and vascular remodeling in development and disease. Dr. Fisher suggested that the regulated expression of myosin phosphatase isoforms determines the sensitivity of smooth muscle to nitric oxide/cGMP-mediated relaxation. He also showed dynamic changes in the expression of myosin phosphatase in a disease model, portal hypertension, characterized by low vascular resistance and high cardiac output, as well as in development. This provides the first example of how regulated smooth muscle gene expression may determine vascular function (resistance) in cardiovascular development and disease.
University of Maryland School of Medicine (Primary)
Charles C. Hong, MD, PhD is the representative at this institution.