Mailing address:
Dr. Yu Tian Wang
Brain Research Center, Room F117
University of British Columbia
2211 Westbrook Mall
Vancouver, BC V6T 2B5

Office: (604) 822-0398
Fax: (604) 822-7299

Research Description:

Glutamate and GABA_A receptors are two principal neurotransmitter receptors, which mediate excitatory and inhibitory synaptic transmission, respectively, in the brain and these receptors play a crucial role in both brain function and dysfunction.  My colleagues and I are interested in understanding molecular mechanisms responsible for the intracellular trafficking and plasma membrane targeting of these receptors, and investigating the manner by which these mechanisms may be altered in CNS disease processes. The goal is, ultimately, to be able to treat central nervous disorders, such as cerebral ischemia and epilepsy, by designing new therapeutics which specifically target these receptors and their pathways.

Selected References:

Bradley C, C Taghibiglou, GL Collingridge, YT Wang, Mechanisms involved in the reduction of GABA_A receptor α1 subunit expression caused by the epilepsy mutation A322D in the trafficking competent receptor, J. Biol. Chem. 283:22043-22050, 2008.

Taghibiglou C, HGS Martin, TW Lai, T Cho, S Prasad, L Kojic, J Lu, Y Liu, E Lo, S Zhang, YP Li, JZZ Wu, YP Li, YH Wen, JH Imm, M Cynader and YT Wang, Role of NMDA receptor-dependent activation of SREBP1 in excitotoxic and ischemic neuronal injuries, Nature Medicine, 15:1399-1406, 2009.

Martin HGS and YT Wang, Blocking the Deadly Effects of the NMDA Receptor in Stroke, Cell 140: 174-176, 2010.

Migues PV, O Hardt, DC Wu, K Gamache, T Sacktor, YT Wang and K Nader, PKMæ maintains memories by regulating GluR2-dependent AMPA receptor trafficking, Nature Neuroscience, 13(5):630-636, 2010.

Wong TP, JG Howland, JM Robillard, Y Ge, W Yu, AK Titterness, K Brebner, L Liu, J Weinberg, BR Christie, AG Phillips, and YT Wang. Hippocampal long-term depression mediates acute stress-induced spatial memory retrieval impairment, Proc Natl Acad Sci, 104:11471-11476, 2007.

Liu Y, TP Wong, M Aarts, A Rooyakkers, L Liu, T Lai, DC Wu, J Lu, M Tymianski, AM Craig, YT Wang, NMDA receptor subunits have differential roles in mediating excitotoxic neuronal death both in vitro and in vivo, J Neurosci, 27:2846-2857, 2007.

Collingridge GL, JTR Isaac and YT Wang, Receptor trafficking and synaptic plasticity, Nature Neuroscience Rev.5:952-962, 2004.

Brebner K, TP Wong, L Liu, Y Liu, P Campsall, S Gray, L Phelps, AG Phillips*, YT Wang* (*equal corresponding authors), Nucleus accumbens long-term depression and the expression of behavioral sensitization, Science,310:1340-1343, 2005.

Liu L, TP Wong, MF Pozza, K Lingenhoehl, Y Wang, M Sheng, YP Auberson, YT Wang, Subtypes of NMDA receptors govern the direction of hippocampal synaptic plasticity, Science, 304:1021-1024, 2004.

Wang QH, LD Liu, L Pei, W Ju, G. Ahmadian, J Lu, YS Wang, F Liu and YT Wang, Control of synaptic strength, a novel function of Akt, Neuron, 38:915-928, 2003.

Nong Y, YQ Huang, W Ju, LV Kalia, G Ahmadian, YT Wang*, MW Salter* (*equal corresponding authors), Glycine binding primes NMDA receptor internalization, Nature, 422:302-307, 2003.

Man HY, QH Wang, WY Lu, G Ahmadian, S DiSouza, L Liu, W. Ju, LE Becker, MP Wymann, JF MacDonald and YT Wang, Activation of PI₃-kinase is required for AMPA receptor insertion during LTP of mEPSCs in cultured hippocampal neurons, Neuron, 38:611-624, 2003.

Aarts M, Y Liu, Lidong Liu, S Besshoh, M Arundine, JW Gurd, YT Wang, MW Salter, M Tymianski, Treatment of ischemic brain damage by uncoupling NMDA receptor- PSD-95 protein interactions, Science, 298:846-850, 2002.

Lu WY, Man HY, Trimble W, MacDonald JF and YT Wang, Activation of synaptic NMDA receptors induces LTP through insertion of AMPA receptors at excitatory synapses in cultured hippocampal neurons, Neuron, 29:243-254, 2001.

Liu F, Wan Q, Pristupa Z, Wang YT* and Niznik HB* (*equal corresponding authors) Direct protein-protein binding enables reciprocal dopamine D₅ and GABA_A receptor cross talk, Nature (Article), 403:274-280, 2000.

HY Man, J Lin, W Ju, G Ahmadian-Bahadorani, LE Becker, M Sheng and YT Wang, Regulation of AMPA receptor-mediated synaptic transmission by clathrin-dependent receptor internalization, Neuron, 25:649-662, 2000.

Wang, YT and D.J. Linden, Expression of cerebellar long-term depression requires clathrin-mediated internalization of postsynaptic AMPA receptors, Neuron, 25:635-647, 2000.

Wan Q, Man HY, Liu F, Niznik HB, Pang SF, Brown GM and YT Wang. Differential modulation of GABA_A function by Mel1a and Mel1b receptors, Nature Neurosci., 2:401-403, 1999.

Wan Q, Xiong ZG, Man HY, Ackerley CA, Braunton J, Lu WY, Becker LE, MacDonald JF and YT Wang, Recruitment of functional GABA_A receptors to postsynaptic domains by insulin, Nature 388:686-690, 1997.

Wang YT and MW Salter, Regulation of NMDA receptors by protein-tyrosine kinases and phosphatases, Nature, 369:233-235, 1994.