Our laboratory is interested in mechanisms governing pathological remodeling of the heart. Using molecular, physiological, and electrophysiological approaches, we study structural, functional, and electrical remodeling events occuring in heart disease. These studies are based on genetic and surgical models of heart disease in animals and cells in culture, as well as patients with hypertrophic heart disease and cardiomyopathy. Specific questions we are studying at present include:
- mechanisms governing the pathological growth response of the myocardium;
- autophagy as a novel mechanism of remodeling that contributes to the transition from stable hypertrophy to heart failure;
- FoxO transcription factors and their governance of cell growth, cell viability, autophagy, and protein degradation;
- mechanisms of Ca2+ metabolism in hypertrophied and failing ventricular myocytes with particular emphasis on transcriptional and post-translational regulation of the L-type Ca2+ channel;
- atrophic remodeling of the myocardium;
- stem cell-based therapy in heart disease, focusing on a niche of progenitor cells harbored within the ventricle, as well as exogenous, adipose tissue-derived progenitors.
RESEARCH INTERESTS
cardiac hypertrophy and failure
molecular signaling
electrophysiological remodeling
RECENT PUBLICATIONS
Ni, Y.G., Berenji, K., Wang, N., Oh, M., Sachan, N., Dey, A., Cheng, J., Lu, G., Morris, D.J., Castrillon, D., Gerard, R.D, Rothermel, B.A., Hill, J.A., "FoxO transcription factors blunt cardiac hypertrophy by inhibiting calcineurin signaling." Circulation, 114:1159-1168, 2006
Kong, Y., Lu, G., Tannous, P., Berenji, K., Rothermel, B.A., Olson, E.N., Hill, J.A., "Suppression of class I and II histone deacetylases blunts pressure-overload cardiac hypertrophy." Circulation, 113:2579-2588, 2006
Wang, Y., Cheng, J., Joyner, R.W., Wagner, M.B., Hill, J.A., "Remodeling of early-phase repolarization: A mechanism of abnormal impulse conduction in heart failure" Circulation, 113:1849-1856, 2006
Tannous, P., Zhu, H., Nemchenko, A., Berry, J.M., Johnstone, J.L., Shelton, J.M., Miller, F.J., Jr., Rothermel, B.A., Hill, J.A., "Intracellular protein aggregation is a proximal trigger of cardiomyocyte autophagy" Circulation, 2008
Tannous, P., Zhu, H., Johnstone, J.L., Shelton, J.M., Soorappan, R., Benjamin, I.J., Nguyen, L., Gerard, R.D., Levine, B., Rothermel, B.A., Hill, J.A., "Autophagy is an adaptive response in desmin-related cardiomyopathy" Proc Natl Acad Sci USA, 2008
SIGNIFICANT PUBLICATIONS
Hill and Olson, "Cardiac Plasticity" N Engl J Med, 358:1370-1380, 2008
Zhu, H., Tannous, P., Johnstone, J.L., Kong, Y., Shelton, J.M., Richardson, J.A., Levine, B., Rothermel, B.A., Hill, J.A., "Cardiac autophagy is a maladaptive response to hemodynamic stress" J Clin Invest, 117(7):1782?1793, July 2007
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