Analyzing the role of dysferlin in skeletal muscle in membrane repair
Our research focuses on the role of dysferlin in resealing the skeletal muscle sarcolemmal membrane after membrane disruption. Current studies will assess if autoantibodies against membrane repair proteins have the potential to influence dysferlinopathy progression by altering the capacity of the membrane to reseal following disruption. Additional studies will test if targeting specific cell signaling pathways related to the induction of membrane repair can increase membrane repair in muscle from dysferlinopathy mouse models. We will evaluate the effects of dysferlin constructs on the membrane repair capacity of muscle cells by utilizing dysferlin variants encoded by cDNAs carrying different point mutations or missing specific exonic sequences or structural domains, many of which are based on variants seen in dysferlinopathy patients. These studies will make use of a laser membrane wounding assay used by us and other laboratories to study the role of dysferlin and membrane repair in skeletal muscle. The results of these studies will help establish the extent that changes in membrane repair capacity contribute to the progression of dysferlinopathy. Understanding the contribution of compromised membrane repair in dysferlinopathies should allow for more effective design of therapeutic approaches to treat these muscular dystrophies.