Michael Rubart, MD
Primary Appointment: Department of Pediatrics
Joint Appointment: Department of Pharmacology & Toxicology
- Research Fellowship: Institute of Naval Medicine, Kronshagen, Germany
Krannert Institute of Cardiology, Indiana University School of Medicine
Department of Pharmacology, University of Vermont, Burlington, Vermont
- Internal Medicine Residency:Technical University Aachen, Aachen, Germany
- M.D.:University of Bonn, Bonn, Germany
Current Research Interests:
a)To understand the role of fibroblast – cardiomyocyte interactions in cardiac electrophysiology
Using a combination of transgenic reporter technology and in situ two-photon fluorescence microscopy-based voltage imaging, we have demonstrated that cardiac fibroblasts, which are intrinsically non-excitable cells, electrotonically couple to neighboring cardiomyocytes in the infarct border zone. Studies ongoing in the laboratory investigate the mechanism underlying heterocellular coupling, including the contribution of gap junctions formed by connexins and/or pannexins, using pharmacological uncouplers as well as cell lineage-restricted genetic ablation of gap junction-forming proteins. Once we have identified the coupling mechanism, we will investigate the electrophysiological consequences of fibroblast-myocyte electrotonic coupling, specifically its role in postinfarction arrhythmogenesis. Other experiments are investigating the role of paracrine signaling in cardiomyocyte-fibroblast communication. Using the patch-clamp technique, we have demonstrated that the cytokine monocyte chemoattractant protein 1 (MCP-1, also named CCL2) released from ‘activated’ cardiac fibroblasts is a potent inhibitor of the major cardiac calcium channel, the voltage-gated L-type calcium channel, via the G?? protein - phospholipase C - protein kinase C signaling pathway. Ongoing studies are examining the consequences of MCP-1 – mediated calcium channel inhibition on cardiomyocyte excitation – contraction coupling using confocal fluorescence microscopy-based imaging of intracellular calcium dynamics. MCP-1 also appears to affect ion channels other than calcium channels, and cellular electrophysiological studies are aimed at identifying these ion channel(s) as well as the underlying signaling pathways.
b) To understand the impact of gene variations / mutations on cardiac and neuronal electrophysiology
In collaboration with the laboratory of Dr. Peng-Sheng Chen at the Krannert Institute of Cardiology, we are characterizing the consequences of newly identified variations / mutations in genes encoding for a calcium-activated potassium channel and a calcium-handling protein, respectively, for the electrophysiological properties of the heart and sympathetic nervous system. These studies utilize a variety of experimental techniques, including CRIPSR/CAS for generation of ‘knock-in” animals, single-cell patch clamping, electrocardiographic recordings in anesthetized and conscious animals, and optical imaging of voltage and calcium signals in living cells / organs.
Office: 1044 West Walnut Street, R4-W359, Indianapolis, IN 46202