Faculty: Susan R. George, MD, FRCP(C), FACP
Canada Reseach Chair for Molecular Neuroscience
Co-Section Head, Molecular Pharmacology, Neuroscience Department, CAMH
General Research Areas: G protein-coupled Receptors, Signal Transduction, Drug Addiction, Neuropsychiatric Disorders
Molecular Pharmacology of Neurotransmitter Transmitters in Brain and Role in Drug Addiction and Psychiatric Disorders
NOT TAKING NEW GRADUATE STUDENTS IN 2015-16
Many important CNS functions are intimately linked to the function of certain neuro-transmitter systems, such as the dopamine, opioid, serotonin and various neuropeptide neuronal systems. We are particularly interested in the G protein coupled receptors for these neurotransmitters, each of which exists as families of closely related proteins. The research focuses on the regulation of receptor function, receptor homo-oligomerization and hetero-oligomerization, second messenger coupling, structure-activity relationships, and brain distribution of the receptors and mRNA. Receptor gene-deleted animal models are studied to define the specific functions of the closely related receptor subtypes, particularly as models to define the receptor systems contributing to the vulnerability to substance abuse and neuropsychiatric disease. State of the art pharmacological, biochemical and molecular biological methodologies are utilized in our studies.
Rashid AJ, O'Dowd BF, Verma V, George SR. Neuronal Gq/11-coupled dopamine receptors: an uncharted role for dopamine. Trends in Pharmacological Sciences, 2007 Nov;28(11):551-5.
Hasbi A, Nguyen T, Fan T, Cheng R, Rashid A, Alijaniaram M, Rasenick MM, O'Dowd BF, George SR. Trafficking of preassembled opioid mu-delta heterooligomer-Gz signaling complexes to the plasma membrane: coregulation by agonists. Biochemistry, 2007 Nov 13;46(45):12997-3009.
Kong MM, Hasbi A, Mattocks M, Fan T, O'Dowd BF, George SR. Regulation of D1 dopamine receptor trafficking and signaling by caveolin-1. Mol Pharmacol. 2007 Nov;72(5):1157-70.
So CH, Verma V, O'Dowd BF, George SR. Desensitization of the dopamine D1 and D2 receptor hetero-oligomer mediated calcium signal by agonist occupancy of either receptor. Mol Pharmacol. 2007 Aug;72(2):450-62.
Rashid AJ, So CH, Kong MM, Furtak T, El-Ghundi M, Cheng R, O’Dowd BF, George SR. D1-D2 dopamine receptor heterooligomers with unique pharmacology are coupled to rapid activation of Gq/11 in the striatum. Proc Nat Acad Sci. USA. 2007 Jan 9; 104(2):654-9.
Kong MM, Fan T, Varghese G, O’Dowd BF, George SR. Agonist-induced cell surface trafficking of an intracellularly sequestered D1 dopamine receptor homo-oligomer. Mol Pharmacol. 2006 Jul;70(1): 78-89.
Fan T, Varghese G, Nguyen T, Tse R, O’Dowd BF, George SR. A role for the distal carboxyl tails in generating the novel pharmacology and G protein activation profile of mu and delta opioid receptor hetero-oligomers. J Biol Chem. 2005 Nov 18;280(46):38478-88.
O'Dowd BF, Ji X, Alijaniaram M, Rajaram RD, Kong MM, Rashid A, Nguyen T, George SR. Dopamine receptor oligomerization visualized in living cells. J Biol Chem. 2005 Nov 4;280(44):37225-35.
So CH, Varghese G, Curley KJ, Kong MM, Alijaniaram M, Ji X, Nguyen T, O'dowd BF, George SR. D1 and D2 dopamine receptors form heterooligomers and cointernalize after selective activation of either receptor. Mol Pharmacol. 2005 Sep;68(3):568-78.
Lee SP, So CH, Rashid AJ, Varghese G, Cheng R, Lança AJ, O'Dowd BF, George SR. Dopamine D1 and D2 receptor Co-activation generates a novel phospholipase C-mediated calcium signal. J Biol Chem. 2004 Aug 20;279(34):35671-8.
Rashid AJ, O'Dowd BF, George SR. Minireview: Diversity and complexity of signaling through peptidergic G protein-coupled receptors. Endocrinology, 2004 Jun;145(6):2645-52.
Lee SP, O'Dowd BF, Rajaram RD, Nguyen T, George SR. D2 dopamine receptor homodimerization is mediated by multiple sites of interaction, including an intermolecular interaction involving transmembrane domain 4. Biochemistry, 2003 Sep 23;42(37):11023-31.
El-Ghundi M, O'Dowd BF, Erclik M, George SR. Attenuation of sucrose reinforcement in dopamine D1 receptor deficient mice. Eur J Neurosci. 2003 Feb;17(4):851-62.
George SR, O'Dowd BF, Lee SP. G-protein-coupled receptor oligomerization and its potential for drug discovery. Nature Reviews Drug Discovery, 2002 Oct;1(10):808-20.
University of Toronto
Department of Pharmacology and Toxicology
Room 4358, Medical Sciences Building
1 King's College Circle