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Skeletal muscle is the largest tissue in the body and accounts for approximately 40% of body mass. It is well established that loss of skeletal muscle mass in humans is correlated with increased mortality and decreased quality of life.
The two major themes in the lab are 1) to determine the molecular signaling mechanisms regulating skeletal muscle growth and 2) to understand the function of circadian rhythm gene expression in skeletal muscle phenotype and function.
These general aims of the lab are approached experimentally by using genetic mouse models [knock outs, conditional knock outs and transgenics] with both in vivo and in vitro measures of muscle phenotype and function. The use of well-defined physiological systems with newly evolving molecular technologies allows for more mechanistic testing of a molecular function in an integrated system.
Muscle Growth Project: Recently our lab has identified that mechanical strain regulates protein synthesis in skeletal muscle through the kinase, mTOR. The downstream functions of mTOR are quite complex as it is a large protein kinase with numerous HEAT repeats that mediate diverse protein-protein interactions. The current projects in the lab use genetic mutants of factors in the mTOR pathway to identify mechanisms by which mechanical strain, nutrients and growth factors regulate the growth process in the differentiated muscle cell.
Circadian Rhythm Project: The molecular clock mechanism exists in skeletal muscle cells as it does in the brain and other peripheral tissues. We have recently determined that disruption of the molecular clock in skeletal muscle leads to profound structural and functional deficits in the adult mouse. Skeletal muscle from clock compromised mice exhibit altered myofibrillar structure, reduced maximum force capacity and reduced mitochondrial volume. Ongoing projects include determining 1) the time cues regulating proper expression of the core clock genes , Clock and Bmal1, in skeletal muscle and 2) transcriptional targets of the core clock genes.
We feel that understanding more about the fundamental nature of circadian rhythms in skeletal muscle may hold important insight into areas such as communication among organ systems and may be critical for disease prevention and rehabilitation strategies.
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