Investigator, Lady Davis Institute
Assistant Professor, Department of Human Genetics, McGill University
Dr. Colin Crist received his BSc from the University of British Columbia and his PhD from the University of Tokyo. He was a post-doctoral research associate in the lab of Margaret Buckingham at the Institut Pasteur (Paris, France). In 2012, he obtained a faculty appointment as an assistant professor at the Lady Davis Institute for Medical Research and the Department of Human Genetics at McGill University. He holds the Marjorie and Gerald Bronfman Chair in Skeletal Muscle Stem Cell research.
Major Research Activities
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 using techniques in molecular biology and genetics toinvestigate the molecular mechanisms regulating MuSC activity. We currently focus on translational control of MuSCs and myogenic progenitors. The major research themes of our laboratory are as follows:
1. 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.
2. microRNA regulators of muscle development. During embryonic development, multipotent progenitors make a cell fate decision to enter the myogenic lineage. We are investigating microRNA contribution to this cell fate decision. We will manipulate microRNA activity to reinforce the muscle cell fate decision to efficiently derive myogenic progenitors from pluripotent stem cells.
3. 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.
4. Genetic regulators of myogenesis. We are using multiple approaches to identify cofactors that facilitate the activity of transcription factors within the contexts of muscle development and disease.
Blanc, R.S., Vogel, G., Chen, T., Crist, C*.and Richard, S*. (2016) Prmt7 preserves satellite cell regenerative capacity. Cell Reports 14, 1528-1539.
Zismanov, V. Chichkov, V., Colangelo, V., Jamet, S., Wang, S., Syme, A., Koromilas, A.E., and Crist, C. (2016) Phosphorylation of eIF2a is a translational control mechanism regulating muscle stem cell quiescence and self-renewal. Cell Stem Cell 18, 79-90.
Crist, C.G., Montarras, D. and Buckingham, M. (2012) The muscle satellite cell is primed for myogenesis, but maintains quiescence with sequestration of Myf5 mRNA targeted by microRNA-31 in mRNP granules. Cell Stem Cell 11, 118-126.
Crist, C.G., Montarras, D., Pallafacchina, G., Rocancourt, D., Cumano, A., Conway, S.J., and Buckingham, M. (2009). Muscle stem cell behaviour is modified by microRNA-27 regulation of Pax3 expression. Proc. Natl. Acad. Sci. 106, 13383-13387. (Featured in Cell 138, 813-814)