Diversity Supplement for A. Christie: Beta Catenin regulation of skeletal muscle hypertrophy

Supplement for underserved minority undergraduate student. The loss of skeletal muscle mass is of clinical importance because it is associated with increased morbidity and mortality as well as a marked deterioration in the quality of life.1 In addition, the growing recognition that skeletal muscle has a significant influence on whole-body metabolism has further heightened interest in determining the molecular mechanisms regulating skeletal muscle mass. The objective of the parent grant is to determine the role of â-catenin in regulating skeletal muscle hypertrophy through c-myc activation of ribosome biogenesis. A study from our laboratory using a viral Cre/loxP system demonstrated that â-catenin was necessary for skeletal muscle fiber hypertrophy.2 This work built on an earlier study from our laboratory reporting â-catenin activation in response to a hypertrophic stimulus resulted in increased expression of c-myc and cyclin D1.2, 3 Our findings are in agreement with studies from the Force laboratory showing the transcriptional activity of â-catenin was necessary and sufficient for the induction of cardiomyocyte hypertrophy.4, 5 While the results of these studies provide strong support for our model i.e, â-catenin regulation of muscle hypertrophy, it is important to note that none of these studies explored the mechanism by which â-catenin regulates hypertrophy. The proposed experiments in the parent grant combine molecular, cell biological and biophysical approaches to understand the mechanisms by which â-catenin regulates skeletal muscle hypertrophic growth. The results of the experiments outlined in the parent grant are expected to have therapeutic implications for the treatment of sarcopenia, muscle wasting/cachexia and problems associated with metabolic diseases such as insulin resistance. In addition, a better understanding of the mechanism by which â-catenin regulates skeletal muscle hypertrophy will likely have applications for rehabilitation therapies for spinal cord injury patients as well as individuals subjected to prolonged periods of bedrest.