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Simon S. Wing, MD, FRCPC Professor, Endocrinology & Metabolism Tel: 514-934-1934 ext. 76184 simon.wing [at] mcgill.ca |
Biographical Sketch
MD,CM, McGill University, 1981
Internal Medicine, McGill University, 1984
Endocrinology and Metabolism, McGill University, 1987
Postdoctoral Fellowship, Dept. of Physiology, Harvard Medical School 1987-89
Postdoctoral Fellowship, National Research Council of Canada Biotechnology Research Institute 1990-93
Member, American Society for Clinical Investigation
Keywords
Ubiquitin, proteasome, muscle wasting, cachexia, metabolism, diabetes, spermatogenesis, male infertility, proteolysis
Research or Clinical Activities
Ubiquitin-proteasome system in skeletal muscle protein degradation
Muscle wasting due to skeletal muscle protein degradation complicates many diseases (e.g. cancer, infection, stroke) as well as normal aging. Our goal is to identify key enzymes in the ubiquitin proteasome system that are responsible for the activation of protein degradation and could be pharmacologically inhibited to prevent or treat muscle wasting. We identified USP19 as a deubiquitinating enzyme that is induced in atrophying skeletal muscle. Our cellular and transgenic knock out studies indicate that this enzyme plays an important role not just in muscle wasting, but has a broader effect on metabolism including physical activity and glucose homeostasis. We are currently exploring mechanisms arid the potential drug targeting of this enzyme.
Ubiquitin-proteasome system during spermatogenesis
Highly regulated degradation of proteins plays important roles in the proliferative, meiotic and cellular remodeling phases of spermatogenesis. We previously demonstrated the activation of ubiquitination during spermatogenesis and have subsequently identified key ubiquitin system enzymes involved in this process such as the Huwe1 ubiquitin ligase and the USP2 deubiquitinating enzyme. We are presently identifying the substrates that mediate their effects.
Selected Recent Publications
Fok KL, Bose R, Sheng K, Chang CW, Katz-Egorov M, Culty M, Su S, Yang M, Ruan YC, Chan HC, Iavarone A, Lasorella A, Cencic R, Pelletier J, Nagano M, Xu W, Wing SS. Huwe1 Regulates the Establishment and Maintenance of Spermatogonia by Suppressing DNA Damage Response. Endocrinology 2017, 158:4000-4016.
Bose R, Sheng K, Moawad AR, Manku G, O’Flaherty C, Taketo T, Culty M, Fok KL, Wing SS. Ubiquitin Ligase Huwe1 Modulates Spermatogenesis by Regulating Spermatogonial Differentiation and Entry into Meiosis. Sci. Rep. 2017, in press.
Bilodeau PA, Coyne ES, and Wing SS. The ubiquitin proteasome system in atrophying muscle – roles and regulation. Amer. J. Physiol. Cell Physiol. 2016, 311:C392-403. (Invited review).
Bédard N, Jammoul S, Moore T, Wykes L, Hallauer PL, Hastings KEM, Stretch C, Baracos V, Chevalier S, Plourde M, Coyne E, Wing SS. Inactivation of the USP19 Deubiquitinating Enzyme Protects Against Muscle Wasting. FASEB J 2015, 29:3889-98. doi: 10.1096/fj.15-270579. Epub 2015 Jun 5.
Wiles B, Miao M, Coyne E, Larose L, Cybulsky AV, and Wing SS. USP19 deubiquitinating enzyme inhibits muscle cell differentiation by suppressing unfolded-protein response signaling. Mol. Biol. Cell 2015, 26: 913-923