Current Research: Alterations of the heart’s molecular motor are associated with both inherited and acquired forms of heart disease. My research is focused on the role that cardiac myosin, the heart’s molecular motor, plays in the pathogenesis of inherited cardiomyopathy and in cases of heart failure. Point mutations of cardiac myosin are frequently associated with inherited cases of hypertrophic cardiomyopathy, a disease associated with sudden cardiac death. In cases of human heart failure, the myosin isoform expression profile shifts to the exclusive expression of a slow motor, while non-failing human hearts express significant levels of a faster myosin motor. We use recombinant viruses to study mutated myosin functionality in single cardiac myocytes in vitro and in the whole heart in vivo. In addition to studying contractile parameters, we also monitor myosin effects on intracellular calcium homeostasis by loading cardiac muscle cells with fluorescent calcium indicators. In other studies we are using recombinant viruses to deliver faster myosin motors to failing hearts and myocytes. Using these molecular genetic and physiological approaches, we are attempting to identify molecular processes that contribute to the pathogenesis of heart disease and to deliver therapeutic myosin genes to diseased hearts. Representative Publication: Herron TJ, Rene Vandenboom, Ekaterina Fomicheva, Lakshmi Mundada, Terri Edwards and Joseph M. Metzger. Calcium independent negative Inotropy by β-myosin heavy chain Gene Transfer in Cardiac Myocytes. Circ Res. 2007; 100: 1182-1190. Herron TJ, Rostkova E, Kunst G, Chaturvedi R, Gautel M, Kentish JC. Activation of Myocardial Contraction by the N-Terminal Domains of Myosin Binding Protein-C. Circ Res. 2006;98:1290-1298. Korte FS, Herron TJ, Rovetto MJ, McDonald KS. Power output is linearly related to myosin heavy chain content in rat skinned myocytes and isolated working hearts. Am J Physiol Heart Circ Physiol. 2005;01227. Haworth RS, Cuello F, Herron TJ, Franzen G, Kentish JC, Gautel M, Avkiran M. Protein Kinase D Is a Novel Mediator of Cardiac Troponin I Phosphorylation and Regulates Myofilament Function. Circ Res. 2004; 95:1091-1099. Herron TJ, McDonald KS. Small Amounts of α-Myosin Heavy Chain Isoform Expression Significantly Increase Power Output of Rat Cardiac Myocyte Fragments. Circ Res. 2002;90:1150-1152. Herron TJ, Korte FS, McDonald KS. Loaded shortening and power output in cardiac myocytes are dependent on myosin heavy chain isoform expression. Am J Physiol Heart Circ Physiol. 2001;281:1217-1222. Herron TJ, Korte FS, McDonald KS. Power Output Is Increased After Phosphorylation of Myofibrillar Proteins in Rat Skinned Cardiac Myocytes. Circ Res. 2001;89:1184-1190.
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