Our research focuses on the origin and regulation of myogenic stem cells in skeletal muscle. Our long-term goal is to identify means to ameliorate age-related muscle deterioration (sarcopenia) and muscle wasting disorders due to muscular dystrophy. Sarcopenia is characterized by a decline in mass, strength, and endurance of skeletal muscles, and by fat accumulation between and within myofibers. Subtle muscle injuries that occur during routine muscle activity raise a continuous demand for functional myofiber repair throughout life. However, myogenic stem cell performance declines in old age and this decline can be a contributory factor to sarcopenia. In Duchenne muscular dystrophy, the myofibers are deteriorating in early age with exhaustion of myogenic stem cells and enhanced presence of inflammatory cells and fibrosis. Hence, the identification of means to deliver donor cells that may be able to support the muscle tissue is important. We investigate satellite cells, classically defined tissue specific myogenic stem cells that reside beneath the myofiber basal lamina, as well as non-myogenic progenitors associated with the microvasculature that may contribute to myogenesis by myogenic reprogramming. We are also interested in the origin and regulation of adipogenic progenitors in skeletal muscles.
Our current main research directions include:
• Mechanisms involved in supporting myogenic commitment and renewal of satellite cells;
The role of FGF-FGFR system in regulating satellite cells;
The role of Klotho genes in the balance between myogenicity and adiposity of skeletal muscle. • Lineage origins and cellular/molecular distinctions of satellite cells from extraocular muscles (EOM) that contribute to enhanced stem cell performance and sparing from muscular dystrophy. • Origin and significance of unconventional progenitors that may function to replace myonuclei during myofiber maintenance. Emphasis is given to the role of cells associated with the microvasculature, in particular the pericytes.
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Fred Hutch | University of Washington
Institute for Systems Biology (ISB)| Center for Infectious Disease Research