One major question I have been exploring is why certain muscles are more severely affected than others in the muscular dystrophies, especially Duchenne and Becker muscular dystrophy. This question is a central one in the pathophysiology of this class of diseases, and the answer may help discover new therapeutic modalities. Initially, I approached this problem using gene expression technology. More recently, I have focused more specifically on the role of utrophin, and plan a series of experiments to elucidate this issue.

My second major laboratory project involves genetic analysis in limb-girdle muscular dystrophy (LGMD). A significant minority of patients with LGMD do not have mutations in the 18 LGMD genes discovered to date. Identification of the remaining genes will help understand the overall muscular dystrophy disease process better. We are analyzing several large kindreds with LGMD using linkage analysis and DNA sequencing tools, and have already identified several novel mutations in known LGMD genes. My hope is to identify novel genes in the future.

Clinical electrophysiological investigations focus on observations in the EMG Laboratory that will assist in the diagnostic evaluation of patients with neuromuscular disease. Additionally, I pursue clinical studies in neuromuscular disease and Cockayne syndrome as opportunities arise. In 2008, we described the first medical treatment for Cockayne syndrome, which may help with some of the neurological complications seen in this disorder. I also participate in a Muscular Dystrophy Association (MDA)-sponsored clinical research network focusing on muscular dystrophy and the Pediatric Neuromuscular Clinical Research Network (PNCR).

My research group consists of a laboratory technician, certified genetic counselor, and various fellows, residents, and technicians who pursue smaller projects with me on a rotating basis.