We translate fundamental insights into therapeutic strategies.
Stem cell transplantation
Transplantation of muscle stem cells is a potentially powerful approach to reverse atrophy of muscles and repair damaged and diseased muscle. We have shown that muscle stem cells (MuSCs) transplanted to damaged tissue can repopulate the muscle stem cell niche, and provide a long-term reservoir for regeneration. Weakness in certain small but key muscles has a disproportionally large deleterious effect, for example in the urinary sphincter muscle. Stress urinary incontinence (SUI) afflicts over six million women in California alone, and is a major cause of commitment to assisted living. MuSC transplant can increase muscle strength, and we are currently investigating the therapeutic potential of this approach by transplanting MuSCs in rodent models with injuries of small muscles such as the urethra. The long term goal is to correct health conditions arising from failure of small muscles.
Enhancing gene therapy
Duchenne muscular dystrophy is caused by a mutation in the dystrophin gene. Clinical trials using gene therapy to deliver functional versions of dystrophin have so far ended in failure, at least in part due to the immune response mounted by the patient against the introduced dystrophin protein. With our collaborators, we are developing immunological approaches to modulate the immune response to gene therapy to overcome this hurdle.
iPS-derived cardiomyocytes enable elucidation of disease mechanisms and testing of thereapeutic strategies.
Bioluminescence imaging non-invasively reveals successful regeneration over time in a mouse MuSC transplant model.