Simon S. Wing

Biography

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

Research Interest

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.