Douglas A. Gray, PhD

dgray@ohri.ca
Telephone: 613-737-7700 ext 70331
Fax: 613-247-3524

Senior Scientist, Cancer Therapeutics, Ottawa Hospital Research Institute

Professor, Depts. of Medicine and Biochemistry, Microbiology and Immunology, University of Ottawa

University of Ottawa Joan Sealy Chair in Lung Cancer Research

Current Research Projects

We are interested in the molecular changes that occur during mammalian aging, and how these changes may predispose the individual to diseases of aging. The diseases of interest are lung cancer and neurodegeneration, both of which show dramatically increased frequencies during the later decades of life. We are particularly interested in age-related changes in the ubiquitin/proteasome pathway (the major pathway for the regulated destruction of cellular proteins). We are studying age-related changes in gene expression in the lungs and brains of mice and humans, and are modelling age-related perturbations in proteolytic pathways using transgenic mice. The involvement of ubiquitin chains in DNA repair is also under investigation using transgenic mice. We continue in our studies of USP4, a deubiquitinating enzyme first identified in the Gray laboratory, hoping to identify its substrates and elucidate its postulated role in lung cancer.

Research Group Members

Senior Research Associate:
Dr. Josée Coulombe
Senior Research Technician:
Mei Zhang, M.Sc.

Graduate Students:
Sophie Bastarache, M.Sc. candidate in the Dept. of Biochemistry,
Microbiology and Immunology
Matthew Tang, Ph.D. candidate in the Dept. of Biochemistry,
Microbiology and Immunology

Summer Student:
Madison Gray
Co-op Student:
David Legault

Recent Publications:

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.

Proctor, C.J., and Gray, D.A. (2010) GSK3 and p53 - is there a link in Alzheimer's disease? Molecular Neurodegeneration 2010, 5:7

Brun, J., and Gray, D.A. (2009) Targeting the ubiquitin proteasome pathway for the treatment of septic shock in patients. Clinical Care, 13:311.

Proctor, C.J., and Gray, D.A. (2008) Explaining oscillations and variability in the p53-Mdm2 system. BMC Systems Biology 2008, 2:75.

Brun, J., Chiu, R.K., Lockhart, K., Xiao, W., Wouters, B.G., and Gray, D.A. (2008) hMMS2 serves a redundant role in human PCNA polyubiquitination BMC Molecular Biology, 2008 9:24

Tsirigotis, M., Baldwin, R.M., Tang, M.Y., Lorimer, I.A.J., and Gray, D.A. (2008) Activation of p38MAPK contributes to polyglutamine-induced cytotoxicity. PLoS One 3(5): e2130 doi:10.1371/journal.pone.0002130.

Proctor, C.J., Tsirigotis, M., and Gray, D.A. (2007) An in silico model of the ubiquitin-proteasome system that incorporates normal homeostasis and age-related decline. BMC Systems Biology 1:17

Langie S.A.S., Knaapen, A.D., Ramaekers, C.H.M.A., Theys, J., Brun, J., Godschalk, R.W.L., van Schooten, F.-J., Lambin, P., Gray, D.A., Wouters, B.G., and Chiu, R.K. (2007) Formation of Lysine 63-linked poly-ubiquitin chains protects human lung cells against benzo[a]pyrene-diol-epoxide-induced mutagenicity. DNA Repair 6, 852-862.