Pathogenesis and genetics of muscular dystrophies.

Dr. Kunkel has devoted his career to understanding the molecular basis, and developing therapy, for neuromuscular disorders. Dr. Kunkel is universally recognized for the identification of the gene and encoded protein, dystrophin, which is altered in boys with Duchenne/Becker muscular dystrophy, in 1986-1987. Recent work has involved the development of a method to introduce the deficient protein into dystrophic muscle and isolation of a group of cells called muscle side population (SP) cells based on their ability to efflux the DNA binding dye Hoechst. These SP cells are isolated by FACS and they can proliferate in culture. Adult skeletal muscle progenitors that exist within the skeletal muscle side population (SP) cells have been shown to extravasate from the circulation and contribute to the regeneration of dystrophic muscle when injected via the tail vein or the femoral artery into non-irradiated murine models for DMD. Current efforts are focused on a better characterization of these cells and maximizing donor cell engraftment by developing more efficient transplantation methods.