TRANSCRIPTIONAL REGULATION OF THE CARDIAC CONDUCTION SYSTEM.
Glenn I. Fishman
Abstract
The cardiac conduction system (VCS) is essential for normal myocardial excitation and contraction. Heritable and acquired syndromes perturbing conduction system formation or function are responsible for a substantial burden of cardiovascular disease, including heart block, triggered and reentrant arrhythmias, sudden cardiac death, myocardial dyssynchrony, and progression of heart failure. Our laboratory has employed stem cell models, genetically encoded conduction system reporter mice, comparative transcriptional profiling, and a battery of functional assays to elucidate the molecular determinants of conduction system development, physiology, and disease pathogenesis. Through these strategies, we have uncovered a diversity of novel conduction system-enriched genes, including transcription factors, receptors, and signaling molecules that modulate conduction system physiology. Our long-term goals are to leverage these discoveries for therapeutic impact and to diminish the burden of diseases resulting from abnormal cardiac rhythmicity.