Current Research:

The heart is an amazing organ, functioning day and night as a mechanical "pump" to circulate blood through the body. It is remarkable that over the lifetime of a healthy individual the heart beats, without fail, over one billion times. Diseases of the heart are the leading cause of death in this country. In heart failure, myocardial ischemia, and cardiomyopathic disease states the normal pumping action of the heart is compromised. One genetic disease studied in our lab is hypertrophic cardiomyopathy (HCM), which directly affects the ability of the heart to perform its pumping function and can lead to premature sudden death, most notably in adolescents and competitive athletes. HCM is caused by mutations in genes that encode key proteins of the cardiac sarcomere, the functional unit of heart muscle. We are interested in understanding the primary defects caused by these mutant gene products in the context of the working muscle cell. This effort involves a systematic manipulation of the multimeric protein assembly of cardiac sarcomere using viral-based gene transfer and transgenic technologies. The long-range goal of our work centers on developing strategies to introduce new genes directly into the heart in attempt to restore normal cardiac pumping action. Our lab also addresses heart failure in myocardial ischemia and in aging.  By transferring healthy genes into the heart, new information will be provided toward developing therapies for the treatment and possible correction of acquired and genetic-based diseases of the heart. 

Our lab is a dynamic and interactive group that spans from graduate students to postdoctoral and clinical fellows, and includes undergraduates, visiting professors and research associates.  Lab expertise ranges from physiologists, bioengineers, cardiologists, surgeons, and molecular and cellular biologists.  We welcome new investigators from diverse academic backgrounds who share our ultimate goal of translating basic science insights into potential clinical therapies for cardiovascular disease. 

Representative Publications:

Yasuda S, Townsend D, Michele DE, Favre EG, Day SM, and Metzger JM. Dystrophic Heart Failure Blocked by Membrane Sealant Poloxamer. /Nature/, 18:1025-9. 2005.

Day SM, Westfall MV, Fomicheva EV, La Cross N, Yasuda S, Hoyer K, Ingwall JS, Metzger JM. Histidine Button Engineered into Cardiac Troponin I Protects the Heart from Ischemic Contractile Failure. /Nature Medicine, /Feb; 12(2):181-9 2006.

Herron TJ, Vandenboom R, Fomicheva E, Mundada L, Edwards T and Metzger JM. Calcium-independent negative inotropy by b-myosin heavy chain gene transfer in cardiac myocytes. /Circulation Research/. 100(8): 1182-90, 2007.

Townsend D, Blankinship MJ, Allen JM, Gregorevic P, Chamberlain JS, Metzger JM. Systemic administration of micro-dystrophin restores cardiac geometry and prevents dobutamine-induced cardiac pump failure. /Molecular Therapy. /; 15(6):1086-92, 2007.

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