Douglas Gray
Senior Scientist Emeritus, Cancer Therapeutics Program
Ottawa Hospital Research Institute
Professor Emeritus, Biochemistry, Microbiology and Immunology
University of Ottawa
Research Interests
The Gray laboratory has studied the molecular changes that occur during mammalian aging, and how these changes may predispose the individual to diseases of aging. The diseases of primary interest were lung cancer and neurodegeneration, both of which show dramatically increased frequencies during the later decades of life. We were particularly interested in age-related changes in the ubiquitin/proteasome pathway (the major pathway for the regulated destruction of cellular proteins) and made extensive use of cell culture systems and transgenic mice to model the decline in proteolytic efficiency. We also combined our laboratory-based experimentation with computational approaches to explore the consequences of such decline. A focus of our studies was USP4, a deubiquitinating enzyme discovered in the Gray laboratory that has been implicated in lung cancer and other forms of neoplasia, and USP15, a closely related enzyme. We delineated the gene duplication event that gave rise to the gene paralogs, and how protein interaction networks were rewired during the evolution of the genes. Another enzyme of interest was UCHL1, a deubiquitinating enzyme that we showed is required for homeostasis of the enteric nervous system.
Brief Biography
Douglas A. Gray received doctoral training as a retrovirologist at the University of Western Ontario and postdoctoral training in insertional mutagenesis at the Whitehead Institute, Massachusetts Institute of Technology. In 1989 he was recruited to the University of Ottawa and established his career as an independent investigator. He has previously held the University of Ottawa Joan Sealy Chair in Lung Cancer and was Professor of Ageing Science at Newcastle University, United Kingdom, from 2009 to 2012. Doug retired from the position of Senior Scientist at the Ottawa Hospital Research Institute in 2022 and is now Senior Scientist Emeritus. He is also Professor Emeritus in the Department of Biochemistry, Microbiology and Immunology at the University of Ottawa.
Selected Publications
Vlasschaert, C., Cook, D., Xia, X., and Gray, D.A. (2017) The Evolution and Functional Diversification of the Deubiquitinating Enzyme Superfamily. Genome Biology and Evolution 9(3):558–573
Vlasschaert, C., Xia, X., and Gray, D.A. (2016) Selection preserves Ubiquitin Specific Protease 4 alternative exon skipping in therian mammals. Scientific Reports 6, 20039.
Vlasschaert, C., Xia, X., Coulombe, J., and Gray, D.A. (2015) Evolution of the highly networked deubiquitinating enzymes USP4, USP15 and USP11. BMC Evolutionary Biology, 15:230
Coulombe, J., Gamage., P., Gray, M., Iqbal., M., Zhang, M., Tang., M.Y., Woulfe, J., Saffrey, J., and Gray, D.A. (2014) Loss of UCHL1 promotes age-related degenerative changes in the enteric nervous system. Frontiers in Aging Neuroscience. | doi: 10.3389/fnagi.2014.00129
Gray, D.A., and Woulfe., J. (2013) Structural disorder and the loss of RNA homeostasis in aging and neurodegenerative disease. Frontiers in Genetics. 4:149. doi: 10.3389/fgene.2013.00149
Tang, M.Y., Proctor, C.J., Woulfe, J., and Gray, D.A. (2010) Experimental and Computational Analysis of Polyglutamine-Mediated Cytotoxicity. PLoS Computational Biology 6(9): e1000944.
Diseases, conditions and populations of interest
Research and clinical approaches
