Rachelle Crosbie

Our laboratory is focused on understanding the function of protein complexes that cause muscular dystrophy and identifying novel mechanisms of therapeutic intervention. Duchenne muscular dystrophy, the most common form of childhood dystrophy, is caused by mutations in the dystrophin gene that result in loss of dystrophin protein and the entire dystrophin-glycoprotein complex. In skeletal muscle, the dystrophin-glycoprotein complex is located at the sarcolemma and is composed of peripheral and integral membrane proteins. As a whole, this complex links the extracellular matrix to the intracellular actin cytoskeleton and provides structural stability to the sarcolemma during muscle contraction. Loss of appropriate connections and contact between the sarcolemma and the extracellular basal lamina has emerged as a critical initiating event of muscle pathology in the muscular dystrophies. Our laboratory has shown that a protein called sarcospan ameliorates muscular dystrophy in mice by increasing levels of several compensatory adhesion complexes that restore connection between the muscle and its surrounding extracellular matrix. We are currently using mouse models to investigate the mechanisms of sarcospan-induced rescue of muscular dystrophy.

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