Medical Student Research Fellowship for Summer 2009

Mentor: Joseph A. Hill, MD, PhD
Department: Internal Medicine / Cardiology
Room number: NB11.200
Mail Code: 8573
Phone number: 8.1400
E-mail: joseph.hill@utsouthwestern.edu (or janet.johnstone@utsouthwestern.edu)
Project title: Molecular Mechanisms of Pathological Cardiac Remodeling

Human subjects IRB approved project number (where applicable):

Animal subjects IRB approved project number (where applicable):
see attached

Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects)

basic research

Brief Description of Project:

Our laboratory is interested in molecular signaling processes in cardiac hypertrophy and failure. Using molecular, physiological, and electrophysiological approaches, we study mechanisms of structural, functional, and electrical remodeling in heart disease. These studies are based on genetic and surgical models of heart disease in animals, 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
" catabolic, atrophy-inducing pathways
" autophagy as a novel mechanism of remodeling that contributes to the transition from stable hypertrophy to heart failure
" 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

Previous Research Activities or Publications with Medical Students:

In several instances, summer students have made substantive contributions to on-going research projects. When this occurs, their efforts are acknowledged with co-authorship on manuscripts. Examples of this include the following:

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.

Wang, Y., Cheng, J., Chen, G., Rob, F., Naseem, R.H., Nguyen, L., Johnstone, J., Hill, J.A. Remodeling of outward K+ currents in pressure-overload heart failure. J Cardiovasc Electrophysiol 18:869-875, 2007.

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 105(28):9745-9750, 2008.

Wang, Y., Tandan, S., Cheng, J., Yang, C., Nguyen, L., Sugianto, J. Johnstone, J.L., Sun, Y. and Hill, J.A. CaMKII-dependent remodeling of Ca2+ current in pressure-overload heart failure. J Biol Chem 283(37):25524-32, 2008.

APN Number Title
0973-06-06-1 Mechanisms of Autophagy in Heart Failure
0973-06-09-1 HDAC Inhibition in Cardiac Hypertrophy and Failure
0973-07-01-2 Hypertrophic Cardiac Remodeling: Functional And Electrophysiological Implications
0973-07-07-1 Calcineurin-Mediated Regulations of Cardiac Ca2+ Channel
0973-07-08-1 Cardiac Hypertrophy: Myocardial Infarction
0973-07-10-1 Cardiomyocyte Autophagy: Regulation by PI3K Signaling
0973-07-11-1 Heterotopic Cardiac Transplantation: A Model of Cardiac Atrophy
0973-07-12-1 Foxo: Negative Regulator of Cardiac Growth
2008-0211 Forkhead Transcription Factors Modulate Insulin Signaling and Contribute to the Patogenesis of Diabetic Cardiomyopathy. Pavan's Fellowship Grant
2008-0370 Foxo: Negative Regulator of Cardiac Hypertrophy
2008-0406 Chemical Regulation of Cardiac Regeneration and Repair
0973-07-04-1 Functional Reconstitution of the Calcium Channel-Calcineurin Regulation
2009-0047 Functional Reconstitution of the Calcium Channel-Calcineurin Regulation (unfinished at this point)