Other School of Medicine Affiliations
Pennsylvania Muscle Institute
Department of Medicine (Division of Cardiology)
Cell and Molecular Biology Graduate Program

Degrees
S.B., Massachusetts Institute of Technology, 1975
A.M., Harvard University, 1980
Ph.D., Harvard University, 1984

Honors
William Maul Measey Chair in Physiology
Fellow of the American Heart Association

Professional Affiliations
Biophysical Society
American Heart Association (Basic Research Council)
American Society for Biochemistry & Molecular Biology
Society of General Physiologists
American Society for Cell Biology

Research Interests
Molecular motors; muscle injury and disease; gene transfer into striated muscle; myofibrillogenesis

Research Description
Dr. Sweeney's research program addresses the molecular basis of cellular movement and force generation. His approach encompasses investigations on single molecules, single cells and whole organisms. At the level of the single molecule, the work examines the basic design and function of the molecular motor, myosin. These studies combine protein engineering with biochemical and structural analyses. At the level of isolated cells (cultured myocytes), the research program has two aspects: 1) investigation of the role of various proteins either in the generation of force, or in the transmission of force across the cell membrane, and 2) the process of assembly of the contractile apparatus. Studies at the whole animal level involve gene transfer into muscle (both germline and somatic cell). Somatic cell gene transfer (utilizing viruses) allows the assessment of acute alterations in cell structure and function following viral-driven expression of a single protein. In response to acute changes in properties, feedback pathways intrinsic and extrinsic to the muscle cell signal alterations in the muscle gene expression program that result in an adaptive response. This new approach allows critical evaluation of principles of muscle cell design as well as evaluation of possible causes of and treatments for muscle diseases. Currently, Dr. Sweeney is studying two diseases, Duchenne muscular dystrophy and hypertrophic cardiomyopathy, with this approach.

Representative Publications
Barton-Davis, E.R., Shoturma, D.I., Musaro, A., Rosenthal, N. and Sweeney, H.L. Viral mediated expression of IGF-I blocks the aging-related loss of skeletal muscle function, Proc. Natl. Acad. Sci. USA 95: 15603-15607, 1998.

Barton-Davis, E.R., Cordier, L.L., Shoturma, D.I., Leland, S.E. and Sweeney, H.L. Aminoglycoside antibiotics restore dystrophin function to skeletal muscles of mdx mice, J. Clin. Inves. 104: 375-381, 1999.

Wells, A.L.,, Lin, A.W., Chen, L.-Q., Safer, D., Cain, S.M., Hasson, T., Carragher, B.O., Milligan, R.A., and Sweeney, H.L., Myosin VI is an actin-based motor that moves backwards, Nature 401: 505-508, 1999.

De La Cruz, E.M., Wells, A.L., Safer, D., Ostap, E.M. and Sweeney, H.L. The kinetic mechanism of myosin V. Proc. Natl. Acad. Sci. USA 96: 13726-13731, 1999.

Rock, R.S., Rice, S.E., Wells, A.L., Purcell, T.J., Spudich, J.A. and Sweeney, H.L., Myosin VI is a processive, backwards motor with a large step size, Proc. Natl. Acad. Sci. USA 98: 13655-13659, 2001.

Coureux, P.D., Wells, A.L., Menetrey, J., Yengo, C.M., Morris, C.A., Sweeney, H.L., Houdusse, A. A structural state of the myosin V motor without bound nucleotide. Nature 425: 419-423, 2003.

Click here for a full list of publications
(searches the National Library of Medicine's PubMed database.)