The focus of the Rentschler lab centers on defining the mechanisms that regulate developmental programming of cellular electrophysiological phenotypes, defining the transcriptional and epigenetic mechanisms underlying cardiac ion channel gene expression, and developing translational approaches for treating arrhythmias. To accomplish these aims, we study cardiac physiology and regulation of gene expression in murine and human model systems. Our group demonstrated that reactivation of developmental signaling pathways including Notch and Wnt can electrically remodel cardiomyocytes, or “reprogram” them, to adopt a new stable electrical phenotype in animal models. In some cases, for example in heart failure, reactivation of the Notch signaling pathway contributes to transcriptional changes influencing ion channel gene expression that predispose to the development of lethal arrhythmias. In the atria, Notch activation in response to pressure overload can predispose to atrial arrhythmias such as sick sinus syndrome. As a step towards translating insights learned through the study of ion channel gene expression in mice into novel therapies for arrhythmias, we developed methodology for culturing organotypic atrial and ventricular cardiac slices from explanted human donor hearts rejected from transplantation. Functional readouts include optical mapping with voltage-sensitive dyes to visualize and quantify electrophysiological properties and assess for cardiac arrhythmias, microelectrode recordings to assess changes in cellular physiology, as well as genome-wide gene expression and epigenetic studies. Through these and other approaches, we aim to decipher the complex regulatory mechanisms that govern ion channel gene expression within regions of the heart in health and disease states, and ultimately advance therapies for patients with arrhythmias.