Research in my laboratory is focused on two main topics: the mechanism of muscular dystrophy and development of therapeutic strategies to treat muscular dystrophy. Alterations in the dystrophin-glycoprotein complex cause several forms of muscular dystrophy, including those with abnormal central nervous system development and function. We are investigating the structure and function of the dystrophin-glycoprotein complex in skeletal, cardiac, and smooth muscle as well as non-muscle tissues including brain and peripheral nerve. In particular, we are interested in the following projects: (1) the post-translational processing of dystroglycan required for its function, (2) the functional role of members of the sarcoglycan-sarcospan complex, (3) the function of dystroglycan within the central and peripheral nervous system including neuronal migration, peripheral nerve conduction, and synaptic plasticity. Muscular dystrophy research in my lab utilizes a variety of biochemical tools and modern genetic approaches, including human patient samples, spontaneous mutant or gene targeted mice, viral gene transfer and stem cell therapy. This research is aimed at understanding disease mechanisms and forming the basis of therapeutic studies in vivo. We have also uncovered a pathway for muscle membrane repair that is responsible for at least two different forms muscular dystrophy not associated with the dystrophin-glycoprotein complex. Current investigations include: (1) the function of dysferlin in membrane repair (2) the membrane repair machinery in skeletal muscle (3) the role of membrane repair in other forms of muscular dystrophy.