Skeletal muscle has a remarkable muscle stem cell dependent capacity for regeneration. Nevertheless, multiple disorders of skeletal muscle, including the family of muscular dystrophies and muscle wasting associated with aging and cancer, represent a major burden on health care systems worldwide. The development of stem cell based regenerative therapies for muscle disease has and will continue to rely heavily on knowledge about embryonic myogenesis and adult regeneration of muscle.
We are addressing these challenges by investigating the molecular mechanisms regulating MuSC activity, with a focus on translational control of MuSCs and myogenic progenitors.
- Translational control of muscle stem cells. Adult stem cells must quickly adapt to environmental cues to activate, proliferate and must make a decision between self-renewal and differentiation. We are investigating translational control mechanisms as first responders regulating gene expression in muscle stem cells.
- The relationship between stem cells and their niche remains a central question in stem cell biology. Skeletal muscle stem cells (MuSCs) normally reside between the plasma membrane of the myofibre and the basal lamina, which is an extra cellular matrix (ECM) structure composed of bridged networks of laminin and collagen polymers. We investigate how ECM interactions with cell surface receptors regulate MuSC activity.
- New therapeutic approaches to muscle disease. By investigating molecular mechanisms that regulate muscle stem cell activity, we identify targetable pathways. We are currently characterizing small compounds that target these pathways towards our goal to increase the potential of muscle stem cells to regenerate muscle.
- Genetic regulators of myogenesis. During embryonic development, multipotent progenitors make a cell fate decision to enter the myogenic lineage. We are using multiple approaches to identify cofactors that facilitate the activity of transcription factors critical to these cell fate decisions.