Current Research:

The focus of my research is to understand the pathophysiology of dystrophic cardiomyopathy and to translate this knowledge into new therapeutic approaches. Much of this work focuses on the cytoskeletal protein dystrophin. Dystrophin is the protein missing in Duchenne Muscular Dystrophy (DMD), functions as a molecular shock absorber, buffering the fragile cellular membrane from the forces generated by striated muscle tissues. Using this knowledge our group discovered a new class of therapeutic membrane sealants. These simple polymeric molecules protect the membranes of the dystrophin deficient mouse heart. Our group is actively working to further assess the effectiveness of these compounds in treating the dystrophin deficient myocardium.

In addition to the structural function described above, dystrophin also forms the nidus of a signaling cluster. The molecules associated with this cluster include neuronal nitric oxide synthase (nNOS), the L-Type Ca2+ channel, caveolin, and many others. Many of these molecules have been implicated in the modulation of cardiac physiology, but the importance of their interaction with dystrophin is largely unexplored. The relevance of this signaling complex extends beyond DMD, as dystrophin is also reduced during heart failure.

Representative Publication:

Townsend, D., Blankinship, M.J., Allen, J.M., Gregorevic, P., Chmaberlain, J.S., and Metzger J.M. Systemic administration of micro-dystrophin restores cardiac geometry and prevents dobutamine-induced cardiac pump failure. Molecular Therapy 15(6):1086-92, 2007.

Chamberlain, J.S., Metzger, J.M., Reyes, M., Townsend, D., and Faulkner, J.A. Dystrophin-deficient mdx mice display a reduced lifespan and are susceptible to spontaneous rhabdomyosarcoma. FASEB J 21(9):2195-204, 2007.

Townsend, D., Yasuda, S., and Metzger, J. Cardiomyopathy of Duchenne muscular dystrophy: pathogenesis and prospect of membrane sealants as a new therapeutic approach. Expert Rev Cardiovasc Ther 5(1):99-109, 2007. [Review]

Yasuda, S.*, Townsend, D.*, Michele, D.E., Farve, E.G., Day, S.M., and Metzger, J.M. Dystrophic heart failure blocked by membrane sealant poloxamer. Nature 436(7053):1025-9, 2005. *-indicates co-first authors.

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