Insights into Arrhythmia Mechanisms and Therapies from Cardiac Reprogramming
Research efforts in the Rentschler lab center on defining the transcriptional and epigenetic mechanisms underlying arrhythmias through studying cardiac physiology and regulation of gene expression in murine, porcine and human model systems. Our group has previously demonstrated that reactivation of developmental signaling pathways including Notch and Wnt can electrically remodel cardiomyocytes, or “reprogram” them, to adopt a new electrical phenotype in animal models. In the atria, Notch activation in response to pressure overload regulates a distinct transcriptional signature in the right versus left atrium and may predispose to atrial fibrillation. In contrast, Notch regulates a distinct transcriptional response in adult ventricular cardiomyocytes resulting in reprogramming to a Purkinje-like phenotype. Noninvasive radiation therapy is a novel treatment for ventricular tachycardia, and we recently deomonstrated that a single high dose of radiation temporarily activates Notch signaling and results in long-term reprogramming of cardiac conduction in normal and diseased hearts. Our work aims to translate insights learned through the study of basic mechanisms of gene expression into novel therapies for arrhythmia.
The recorded seminar can be viewed here.
