Our group is focused on stem cells in postnatal skeletal muscle as well as the role of cell stress effectors during muscle atrophy (muscle wasting). In particular, we have made progress in the role of the master tumour suppressor gene, p53 in governing muscle responses to inflammatory signals such as tumour necrosis factor-alpha (TNF-alpha) and its interaction with a p53 effector gene we identified called PW1. A striking observation is that tumour-mediated or inflammatory triggered muscle wasting does not occur in the absence of p53 function suggesting a novel systemic role for this gene beyond tumour suppression. Furthermore, PW1 is also a marker of pluripotent stem cells in muscle tissue and is expressed by muscle satellite cells as well as a novel interstitial population of muscle stem cells we call PICs. This dual identity suggests interplay between stem cell stress and muscle homeostasis. While this research is fundamental in nature, the implications are clear for potential clinical application.  Most strikingly, we have recently discovered that PW1 expression in the adult is present in many stem cell lineages including the skin, intestine and brain. This may have wide ranging implications for stem cell based therapies. We are presently attempting to characterize what factors will ‘mobilize’ these stem cells to participate more effectively in regeneration and tissue repair as a means to develop non-invasive therapies for multiple degenerative pathologies as well as ageing. 

Lastly, we have been investigating the question as to why secondary tumour formation in skeletal muscle is so rare (metastasis). This line of study has recently demonstrated that skeletal muscle secretes factors that specifically kill metastatic cancer cells but spare normal cells. This work underlines the wide-ranging potentials of basic research.

 

 

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