王以政博士简介

生物谷

Yizheng Wang, Ph.D.

Rm 329, ION Building
Institute of Neuroscience
Chinese Academy of Sciences
Shanghai 200031,
China
Email: yzwang@ ion.ac.cn
Phone: 86-21-5492 1793

Dr.Yizheng Wang is an Investigator and Head of the Laboratory of Neuronal Signal Transduction at ION. He earned his medical degree from the China Medical University 1982 and received his Ph. D. from the University of Laval, Canada in 1991. He was a postdoctoral fellow at University of Nice, France and Case Western Reserve University, USA during 1991-94. He has served as a faculty member at National Research Council of Canada and Thomas Jefferson University, USA before joining ION in 2001. His main researsh interest is the signal transduction involving, G-proteins and protein kinase cascade, and the molecular mechanisms underlying neuronal apoptosis.

Research Interests
	Neuronal signal transduction plays an important role in the regulation of neuronal activities. G-proteins and protein kinase cascades are key parts of the signal transduction. The ongoing research projects include the study of the mechanism and the consequence of activation of Gi by glutamate, the main excitatory neurotransmitter in the central nervous system, and the study of the potential role of PI-3 kinase and MAP (Mitogen-activated protein) kinase cascade in preventing/inducing neuronal apoptosis. A variety of methods of molecular biology, cellular biology and biochemistry are employed to investigate these problems, using primary neuronal cultures, cell lines, as well as animal model systems. Under physiological conditions, glutamate mediates excitatory neurotransmission and synaptic plasticity, e.g., long-term potentiation/depression. However, overstimulation of glutamate receptors, particularly the NMDA and AMPA subtypes, is thought to contribute to a variety of pathological conditions, including epilepsy, stroke and various neurodegenerative diseases. The neurotoxicity, including necrosis or apoptosis, associated with NMDA and AMPA receptor overstimulation is likely to arise, at least in part, from the negative impact it has on cell signaling pathways normally associated with these receptors. Thus, a clearer understanding of the cellular signals triggered by the various glutamate receptors under normal and pathological conditions could lead to the identification of novel intracellular targets for future drug development. To this end, we have recently shown that, while both NMDA and AMPA stimulate p42 mitogen-activated protein (MAP) kinase in neurons, only AMPA-induced MAP kinase activity is inhibited by pertussis-toxin. Furthermore, AMPA stimulates MAP kinase via a novel mechanism in which the G-protein bg dimers released from a Gabg complex bind to a ras protein complex and cause a sequential activation of ras, raf kinase, MEK-1 and MAP kinase. This observation has led to our current study on the role of Gi-protein in the AMPA signaling. Another interest in our laboratory is to investigate the role of protein kinase cascade and ion homeostasis in apoptosis of neurons. A mechanism involving bcl-2/Bax regulation and ion homeostasis was shown to account for the apoptotic process.

Ongoing Projects
	Neuronal signal transduction plays an important role in the regulation of neuronal activities. G-protein and protein kinase cascade are key part of the signal transduction. Glutamate is a main excitatory neuro-transmitter in the central nervous system. The ongoing projects include: Investigation of the mechanism and the consequence of activation of Gi-protein by glutamate. Study of the potential role of PI-3 kinase and MAP (Mitogen-activated protein) kinase cascade in preventing/inducing neuronal apoptosis. The methods of molecular biology, cellular biology and biochemistry are used to investigate the above problems. Primary neuronal cultures, cell lines combined with the animal are our models.

	Publications
	Regan, R., Wang Y., Ma, X., Chong, A., and Guo,Y. (2001) Activation of extracellular regulated kinases potentiates hemin toxicity to astrocyte cultures. J. NeuRochem., 79: 545-555 Wang, Y., Guan, J., Wang, H., Wang, Y., Leeper, D. and Iliakis, G. (2001) Regulation of DNA replication after heat shock by RPA-nucleolin interactions. J. Biol. Chem., 276: 20579-20588 Bourbon, N., Berkey, D., Wang, Y., and Kester, M. (2001) Ceramide differentially regulates PKC/MAPK interaction: Implications for growth arrest. Amer. J. Physiol. (Cell Physiol.) 280: C1403-C1411 Tauskela, J., Chavravarty, B., Murray, C., Wang, Y., Coma, T., Hogen, M., Hakim, A., and Morley, P. (1999) Evidence from cultured rat cortical neurons of differences in the mechanism of ischemic preconditioning of brain and heart. Brain Res., 827: 143-151 Mandal, A., Wang, Y., Ernsberger, P. and Kester, M. (1997) Il-1-induced ether-linked diglycerides inhibit calcium-insensitive PKC isotypes: implications for growth senescence. J. Biol. Chem., 272: 20306-20311 Wang, Y., Samll, D., Stanimirovic, D., Morley, P. and Durkin, J. (1997) AMPA-mediated regulation of a Gi-protein in cortical neurons. Nature, 389: 502-504. Wang, Y., Schramek, H. and Dunn, M. (1996) Cytosolic and nuclear mitogen-activated protein kinases are regulated by two distinct mechanisms. Exp. Cell. Res., 225: 382-388 Wang, Y., and Durkin, J. (1995) AMPA, but not NMDA, activates MAP kinase through G-protein bg subunits in rat cortical neurons. J. Biol. Chem., 270: 22783-22787