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Molecular Basis of Muscular Dystrophy

The Campbell Lab is interested in elucidating the molecular basis of muscular dystrophy, and developing therapeutic strategies to treat muscular dystrophy.

Muscular dystrophies, a group of genetic diseases that primarily affect skeletal muscle, are characterized by progressive muscle weakness. Duchenne muscular dystrophy is caused by mutations in the dystrophin gene that lead to the complete absence of dystrophin in skeletal muscle. Research in my laboratory on the function of dystrophin led to the discovery of the skeletal muscle dystrophin-glycoprotein complex, which spans the muscle cell membrane and links the sub-sarcolemma actin cytoskeleton to the surrounding basement membrane. Defects in genes that encode either components of the complex itself or mediators of its requisite post-translational modifications lead to distinct forms of muscular dystrophy.

Our current and future research focuses on eight related areas:

(1) the molecular pathogenesis of dystrophin glycoprotein complex disorders
(2) the mechanistic basis of maintaining muscle membrane integrity
(3) the molecular pathogenesis of disorders arising from defects in dystroglycan glycosylation
(4) the structural basis of dystroglycan function as a basement membrane receptor
(5) O-mannosyl phosphorylation of α-dystroglycan
(6) LARGE is a bifunctional glycosyltransferase
(7) LARGE-glycan function
(8) dystroglycan mutation associated with muscular dystrophy.

Campbell Laboratory; 285 Newton Road, 4283 Carver Biomedical Research Building, Iowa City, IA 52242