Developmental Genetics, Skeletal Muscle Development and Repair
Muscle development and repair of postnatal skeletal muscle is dependent on the activation and differentiation of myogenic progenitor cells that display stem cell-like properties. This is a potentially exploitable cell population for developing cell therapy approaches for muscle loss associated with degenerative diseases, trauma, and aging. A growing body of evidence has revealed a complex role for the innate immune response in efficient muscle repair through clearance of necrotic fibers and promotion of myogenic cell proliferation and differentiation. This is dependent on pro- and anti-inflammatory macrophage produced cytokines and chemokines. Further, chronic inflammation associated with persistent necrosis of dystronopathies leads to the production of fibrosis and reduced muscle contractility. Before any cell therapy can be incorporated into clinical practice it will be necessary to characterize the genetic and biochemical basis for the regulation of muscle cell self-renewal and differentiation and the contribution of the inflammation response. This represents an important step for enhancing the self-renewal of engrafted cells, and thus their regenerative potential as therapies for myopathies.
1) Examine the role of the protein Numb in regulating the switch between proliferation and differentiation of myogenic progenitor cells.
2) Investigate the role of Mohawk, a novel homeodomain transcription factor, in the regulation of inflammation and myogenic progenitor cells proliferation and differentiation during skeletal muscle regeneration.
3) Examine the signaling pathways leading to the de novo regeneration of skeletal muscle using the green anole as a model system.
4) Examine the genes responsible for early necrotic events in Muscular Dystrophy using C. elegans as a model.