Faculty

George S. Robertson, PhD

Professor

BSc, PhD (Dalhousie University)

Keywords

Neurodegenerative disorders, apoptosis, gene therapy, inflammation, drug discovery, genetic disease models

Current Research

My laboratory is engaged in several projects that are addressing the role of programmed cell death or apoptosis in neurodegenerative disorders such as Alzheimer's disease, stroke, Parkinson's disease and multiple sclerosis. Apoptosis is a highly conserved biological process that orchestrates the orderly dismantling and removal of extraneous cells from the body. Maturation of both the central nervous system (CNS) and the immune system is mediated by the elimination of redundant cells that fail to establish synaptic connections or productive antigen specificities, respectively. My research is based on the premise that dysfunction of the biochemical machinery responsible for apoptosis in the CNS and immune system may contribute to the pathogenesis of a wide variety of neurodegenerative disorders. Accordingly, treatments capable of modulating apoptosis may have broad utility in the treatment of degenerative illnesses of the CNS.

Apoptosis is executed by a specific class of proteases known as caspases that dismantle a cell by systematically cleaving proteins essential to metabolic and structural integrity. Opposing cellular destruction by caspases are proteins encoded by the inhibitor of apoptosis (IAP) family of anti-apoptotic genes. We have shown that adenovirally-mediated over-expression of IAP proteins in the CNS reduces neuronal loss in experimental models of stroke and Parkinson's disease. Moreover, neurons protected from death by IAP over-expression operate properly following transient cerebral ischemia or administration of the dopaminergic neurotoxin MPTP suggesting that treatments which up-regulate IAP expression may be therapeutic in stroke and Parkinson's disease. A major goal of my research is to identify small molecules and biological factors capable of reducing neuronal injury by inducing IAP expression in the CNS.

Inflammatory processes have been implicated in neuronal loss in both acute and chronic neurodegenerative disorders. A second major research focus of my laboratory is to determine the extent to which inflammation contributes to neuronal loss and behavioral deficits in several neurodegenerative contexts. In the case of multiple sclerosis, failure of auto-reactive T cells to undergo apoptosis may promote inflammatory processes responsible for destruction of the myelin sheath. Accumulating evidence suggests that in multiple sclerosis increased expression of the IAP proteins may be responsible for the resistance of auto-reactive T cells to apoptosis. In collaboration with the Apoptosis Research Centre at the University of Ottawa, we are utilizing a variety of experimental approaches to determine whether the IAP proteins are involved in the pathogenesis of multiple sclerosis.

Selected Publications

Selected Publications

Hebb, A.L., Moore, C.S., Bhan, V., Robertson, G.S. (2010) Effects of IFN-B on TRAIL and Decoy Receptor expression in different immune cell populations from MS Patients with distinct disease subtypes. Autoimmune Dis. 2011: 485752.

Samson, M.S., Kajitani, K., Robertson, G.S. (2010) Nitric oxide synthase mediates the ability of darbepoetin alfa to attenuate pre-existing spatial memory deficits in rats subjected to transient global ischemia. Journal of Pharmacology and Experimental Therapeutics 333(2):437-444.

Moore, C.S., Hebb., A.L.O., Blanchard, M.M., Crocker, C.E., Liston, P., Korneluk, R.G, Robertson, G.S. (2008) Increased X-linked inhibitor of apoptosis (XIAP) expression exacerbates experimental autoimmune encephalomyelitis. J. Neuroimmunology 203(1):79-93.

Soundararajan, R., Wishart, A.D., Rupasinghe, H.P., Arcellana-Panlilio, M., Nelson, C.M., Mayne, M., Robertson GS. (2008) Quercetin-3-glucoside protects neuroblastoma (SH-SY5Y) cells in vitro against oxidative damage by inducing SREBP-2 mediated cholesterol biosynthesis. J. Biol. Chem. 283(4):2231-45.

Hebb, A.L.O., Moore, C.S., Bhan, V., Campbell, T., Fisk, J., Thorne, M., Lacasse, E., Holcik, M., Gillard, L., Crocker, S.J., Robertson, G.S. (2008) Expression of the Inhibitor of Apoptosis Family in Multiple Sclerosis Reveals a Potential Immunomodulatory Role during Autoimmune Mediated Demyelination. Multiple Sclerosis 14: 577-594.

Hori SE, Powell KJ, Robertson GS. (2007) Darbepoetin alfa (Aranesp) improves recognition memory in adult rats that have sustained bilateral ventral hippocampal lesions as neonates or young adults. Neuroscience. Jan 5;144(1):1-7.

Robertson GS, Hori SE, Powell KJ. (2006) Schizophrenia: an integrative approach to modelling a complex disorder. Journal of Psychiatry Neuroscience. May;31(3):157-67.

Crocker SJ, Liston, P, Anisman, H., Lee, C.J., Earl, N., Park D.S., Korneluk, R.G., and Robertson GS. (2003) Inhibition of calpains prevents neuronal and behavioral deficits in an MPTP mouse model of Parkinson's disease. J Neurosci. May 15;23(10):4081-91.

Crocker SJ, Smith PD, Jackson-Lewis V, Lamba WR, Hayley SP, Grimm E, Callaghan SM, Slack RS, Melloni E, Przedborski S, Robertson GS, Anisman H, Merali Z, Park DS. (2003) Inhibition of calpains prevents neuronal and behavioral deficits in an MPTP mouse model of Parkinson's disease. J Neurosci. May 15;23(10):4081-91.

Contact Information

Department of Pharmacology
Laboratory of Molecular Neurobiology
Room 15-F1, 15th Floor
Sir Charles Tupper Medical Building
Dalhousie University
5850 College Street
Halifax, Nova Scotia
Canada B3H 1X5

Phone: 902-494-1528

Fax: 902-494-1388

Email: George.Robertson@dal.ca