Duchenne muscular dystrophy (DMD) is a progressive muscle degenerative disease that affects 1 in 3500 to 5000 boys born worldwide and is caused by the absence of a functional protein, dystrophin. There are multitudes of cellular dysfunctions that are associated with the pathophysiology of DMD, including dysregulation of autophagy. I’m interested in better understanding the role of autophagic dysfunction in dystrophic muscles. A previous study from our lab using a rodent model of DMD identified lysosomal insufficiency and impaired degradation of autophagosomes in dystrophic muscle. These dysregulations were shown to be partially rectified by overexpression of PGC-1α, which stimulated lysosomal biogenesis, and decreased disease-related injury. These findings point at the potential therapeutic role of lysosomal biogenesis and effective autophagy in dystrophic muscles. In order to understand this better, we are manipulating the expression of a transcription factor that regulates lysosomal biogenesis in a rodent DMD model.
We are also interested in the interaction of obesity/insulin resistance and dystrophin deficiency. Obesity is observed in more than 50% of DMD patients and more than 70% are overfat. How these factors impact disease progression are unknown, however, insulin resistance and dystrophin deficiency share some pathological mediators, including dysfunction of autophagy, and have some that are unique, providing the opportunity for additive and even synergistic effects.