Novel Regulators of Cardiac Rhythm
Stream Seminar Video
Our laboratory has been interested in multiple facets of cardiac electrophysiology and arrhythmia mechanisms, with a particular focus on identifying novel regulators of cardiac excitability, impulse propagation, and arrhythmia susceptibility. Our most recent studies seek to decipher the mechanisms responsible for specification, maturation and function of the specialized cardiac conduction system and identifying novel transcriptional regulators that influence cardiomyocyte electrophysiological diversity and integrated cardiac excitability. I will describe the role of two novel transcription factors (one recently reported and the second still a work in progress) that appear to play critical roles in establishing functional diversity throughout individual compartments of the heart, including the specialized ventricular conduction system. Ongoing experiments suggest that modulation of transcription factor activity may potently influence cardiac excitability, raising the possibility of potential therapeutic applications. I will also describe our latest studies of fibroblast growth factor homologous factors (FHFs). FHFs comprise a family of intracellular proteins that potently regulate cardiac sodium channel (VGSC) gating and whose deficiency in the mouse produces a rather surprising and remarkable diversity of cardiac phenotypes, including temperature-sensitive conduction failure, arrhythmogenesis, and ventricular remodeling. Computer modeling of individual ventricular myocytes and strands of myocytes in the presence or absence of FHFs, in concert with empiric studies in genetically engineered mouse models, suggest that the well-accepted relationships between junctional conductance (Gj), maximal available sodium conductance (INa,max), conduction velocity (CV) and safety factor (SF) for conduction described by existing models are predicated upon the expression of FHF proteins within cardiomyocytes.
William Goldring Professor of Medicine & Director of the Leon H. Charney Division of Cardiology NYU School of Medicine Dr. Fishman received his undergraduate degree in Chemistry from Cornell University College of Arts & Sciences and his M.D. from Stanford University School of Medicine. He subsequently completed his internship and residency in Internal Medicine at Massachusetts General Hospital, followed by a fellowship in clinical Cardiology at Columbia-Presbyterian Medical Center and a research fellowship in Molecular Cardiology at Albert Einstein College of Medicine. Dr. Fishman joined the faculty at Einstein and rose to the rank of Associate Professor of Medicine and Molecular Genetics, and Director of their Molecular Cardiology Program. He was then recruited to Mount Sinai School of Medicine, where he was named the Fishberg Professor of Medicine and Director of the Section of Myocardial Biology. In 2001, Dr. Fishman joined the faculty of the NYU School of Medicine where he serves as Director of the Leon H. Charney Division of Cardiology, Chief of Cardiology at NYU-Langone Medical Center and the William Goldring Professor of Medicine, Professor of Physiology & Neuroscience, and Professor of Molecular Pharmacology. In 2013 Dr. Fishman was also appointed Vice-Chairman for Research for the Department of Medicine. Dr. Fishman is internationally known for his research on the molecular pathogenesis of cardiovascular diseases. He is especially interested in understanding the mechanisms of cardiac arrhythmias and developing novel strategies for their treatment. Dr. Fishman has served on the Editorial Boards of a number of major biomedical journals including Circulation, Circulation Research, FASEB Journal, Journal of Molecular and Cellular Cardiology, and is currently Associate Editor of Circulation: Arrhythmia and Electrophysiology. Dr. Fishman is the recipient of numerous grants and awards, including a Physician-Scientist Award from the National Institutes of Health, the Louis Katz Basic Science Award for Young Investigators, an Established Investigator Award from the American Heart Association and the Burroughs-Wellcome Fund Clinical Scientist Award in Translational Research and the American Heart Association Basic Research Prize. Dr. Fishman has been inducted into the American Society of Clinical Investigation, the Harvey Society, the Association of University Cardiologists and the Association of American Physicians, and is a Fellow of the American College of Cardiology, the American Heart Association, and the Heart Rhythm Society. He has served as Chairman of the Research Committee and as a member of the Board of Trustees of the American Heart Association Founders Affiliate, on the Board of Trustees of the Heart Rhythm Society, and as President of the Cardiac Electrophysiology Society.