Muscular Dystrophy

Description of projects available to graduate students:
Muscular dystrophies are progressive, genetically determined, and degenerative myopathies. Duchenne muscular dystrophy (DMD) is one of the most common and severe forms of muscular dystrophy. DMD is characterized by progressive weakness in every case, leading to inability to walk within ten years of the onset. Mutations in the dystrophin gene are responsible for lack of expression of the dystrophin protein. The muscle degeneration observed in DMD patients is the result of lack of dystrophin. However, how lack of dystrophin induces DMD is not fully understood. Our laboratory is interested in identifying the molecular mechanisms underlying Duchenne muscular dystrophy. We are focused on investigating the role of caveolin-3 in skeletal muscle. Caveolin-3 is the principal structural component of caveolae, invaginations of the plasma membrane, in skeletal muscle. Muscle cell caveolae have been shown to organize dystrophin and its associated glycoproteins at the plasma membrane. Importantly, caveolin-3 expression is up-regulated in Duchenne’s patients. Interestingly, we have recently demonstrated that over-expression of caveolin-3 in mice as a transgene is sufficient to promote a Duchenne-like muscular dystrophy phenotype. Over-expression of caveolin-3 promotes down-regulation of dystrophin and severe muscle degeneration. We are currently investigating, at the molecular level, the hypothesis that caveolin-3 directly contributes to the muscle degeneration observed in Duchenne muscular dystrophy.

Techniques graduate student will learn:
The laboratory is set up to conduct experiments that employ cellular and molecular biology techniques, including: Southern Blotting, Northern Blotting, PCR, DNA cloning, Western blotting, Immunoprecipitation analysis, Cell Culture, Transient and Stable Transfections, Confocal Microscopy, Transgenic and knock-out mice technologies.