Areas of Interest
I have been an independent investigator since 1980 and currently serve as Co-Director of the Center for Arrhythmia Research and Director of the Cardiovascular Research Center at the North Campus Research Complex, University of Michigan. I enjoy a solid reputation as a productive researcher who focuses on bringing modern biophysical concepts to increase the understanding of the mechanisms of life-threatening cardiac arrhythmias, from the molecule to the bedside. I have studied the role of ion channels in mechanisms of cardiac excitation, intercellular communication and impulse propagation and the underlying bases of acquired and inheritable cardiac arrhythmias for more than 35 years. I have many years of experience using genetically modified mouse models as well as molecular, patch-clamping and optical mapping techniques in the study of cardiac excitability and fibrillation. My laboratory was first to demonstrate that the cardiac sodium channel (NaV1.5) and inward rectifier potassium channels (Kir2.1 and Kir2.2) are part of a common macromolecular complex, a channelosome, and that interactions through SAP97 and a-synthrophin at the intercalated disc and lateral membrane, respectively, provide a means for their reciprocal regulation, with important functional consequences for myocardial excitation, conduction velocity, and arrhythmogenesis. More recently we established single cell, 2D-monolayers and 3D-microtissue platforms of human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CMs) to investigate arrhythmogenic mechanisms in cardiac diseases, including catecholaminergic polymorphic ventricular tachycardia, drug-induced cardiotoxicity and hypertrophic cardiomyopathy. We have made major strides in the purification and maturation of hiPSC-CMs in 2D and 3D. The results represent a significant advance toward the use of these promising cells for patient-specific disease modeling. Altogether, my research experience and skill, together with our advanced models provide strong assurance of my qualifications to lead this project.