Simon S. Wing
Simon S. Wing, MD, FRCPCProfessor, Department of Medicine
Program Director, Experimental Therapeutics and Metabolism Program, RI-MUHC
Polypeptide Laboratory, Strathcona Anatomy & Dentistry Bldg, Room W315
3640 University St., Montreal, QC, H3A 0C7
simon [dot] wing [at] mcgill [dot] ca
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
Ubiquitin, proteasome, muscle wasting, cachexia, 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 in muscle wasting. We are currently exploring mechanisms and 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 are now identifying key ubiquitin system enzymes involved in this process. We purified the ubiquitin ligase Huwe1 from the testis and have recently observed in gene knockout studies that it is required for several steps in spermatogenesis. We also demonstrated that the USP2 deubiquitinating eznyme is induced in late elongating spermatids and is required for fertilization. We are presently determining the cellular and molecular mechanisms underlying these important functions.
Selected Recent Publications
Liu Z, Oughtred R, and Wing SS. Characterization of E3Histone, a novel testis ubiquitin protein ligase which ubiquitinates histones. Mol. Cell. Biol. 2005; 25: 2819-2831
Lu Y, Adegoke OAJ, Nepveu A, Nakayama KI, Bedard N, Cheng D, Peng J and Wing SS. USP19 Deubiquitinating Enzyme Supports Cell Proliferation by Stabilizing KPC1, a Ubiquitin Ligase for p27Kip1. Mol. Cell. Biol. 2009, 29: 547-558
Sundaram P, Pang Z, Miao M, Yu L and Wing SS. USP19 Deubiquitinating Enzyme Regulates Levels of Major Myofibrillar Proteins in L6 Muscle Cells. Amer. J. Physiol. Endo & Metab 2009, 297: E1283-E1290.
Bedard N, Yang Y, Gregory M, Cyr DG, Suzuki J, Yu X, Clarke H, Chian RC, Hermo L, O’Flaherty C, Smith CE and Wing SS. Mice Lacking the USP2 Deubiquitinating Enzyme have Severe Male Sub-Fertility Associated with Defects in Fertilization and Sperm Motility. Biol. Repro. 2011, 85: 594-604.
Yang Y*, Duguay D*, Bedard N, Rachalski A, Baquirin G, Na CH, Fahrenkrug J, Storch F, Peng J, Wing SS+ and Cermakian N+. Regulation of behavioural circadian rhythms and clock protein PER1 by the deubiquitinating enzyme USP2. Biology Open 2012, 1: 789-801, doi: 10.1242/bio.20121990.