Zhengui Xia

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University of Washington
School of Public Health and Community Medicine
Environmental Health
Toxicology
Professor
University of Washington
School of Medicine
Pharmacology
Adjunct Professor
University of Washington
Graduate School
Neurobiology and Behavior Program
Professor
University of Washington
Graduate School
Molecular and Cellular Biology Program
Professor
Professional Headshot of Zhengui Xia

Mailing Address

Box 357234
Seattle, Washington 98195
United States

Contact Information

Phone: (206) 616-3634
Fax: (206) 685-3990
zxia@u.washington.edu

Qualifications

Ph.D., University of Washington, Pharmacology, 1991.
M.S., Wuhan University, Biochemistry, 1985.
B.S., Wuhan University, Biochemistry, 1982.

Expertise and Research Interests

Mechanisms for regulation of apoptosis in animal cells; mechanisms of neurogenesis

One of our research interests is to elucidate signal transduction mechanisms that regulate the fate of neural stem cells, i.e. what makes a neural stem cell proliferate and differentiate into neurons or glia in the mammalian brain. We are interested in neural stem cell regulation both during development and in adult neurogenesis. Specifically, recent studies in our lab suggest a novel role for the extracellular-signal-regulated kinase 5 (ERK5) MAP kinase in regulating the fate choice of cortical stem cells during development. The elucidation of molecular mechanisms that regulate neural progenitor cell proliferation and differentiation is important for an understanding of neural developmental and neurodegenerative diseases. Furthermore, stem cell-based cell replacement therapy offers enormous potential for the treatment of a variety of developmental, psychiatric, neurodegenerative and aging related diseases for which there are currently no cures. Moreover, environmental toxicants may cause developmental neurotoxicity by perturbing these signaling mechanisms that regulate neurogenesis.

Our laboratory is also interested in molecular mechanisms and signal transduction pathways that regulate neuronal survival and cell death. It has become increasingly evident that many environmental toxicants might contribute to the development of neurodegenerative disorders including Parkinson's disease, Huntington's disease, and Alzheimer's disease. Our recent effort has focused on elucidating signaling mechanisms that regulate dopaminergic neuron cell death in relation to Parkinson's disease using exposure to several pesticides as model systems. It is our hope that these mechanistic studies may ultimately lead to the development of pharmacological interventions and clinical strategies for treatment of Parkinson's disease. These studies may also provide insights concerning the relationships between environmental toxicants and the etiology of neurodegenerative disorders.

Keywords

COS Keywords:

Alzheimer's Disease, Animal Diseases Or Pathology, Animal Physiology Or Morphology, Apoptosis, Biochemistry, Cancer Biology, Cancer Or Carcinogenesis, Cell Biology, Cell Proliferation, Environmental Health, Molecular Biology, Neurobiology, Neurogenesis, Pharmacology, Signal Transduction, Stem Cells, Toxicology.

Additional Terms:

Apoptosis, Cancer, Development, Kinases, Neural Development, Neural Stem Cell, Neurodegeneration, Neurogenesis, Neuron, Neuroprecursor Cell Proliferation, Programmed Cell Death, Signal Transduction.

Languages

(Reading, Writing, Speaking)

Chinese, Mandarin: (Fluent, Fluent, Fluent)
English: (Fluent, Fluent, Fluent)

Honors and Awards

1999-2004, Burroughs Wellcome New Investigator Award, Burroughs Wellcome Fund, University of Washington, Toxicology
1997-2000, Sheldon Murphy Assistant Professor, Sheldon Murphy Endowed Chair, University of Washington
1995-1996, Postdoctoral Fellowship, NIH Training Grant, Harvard University
1993-1995, Postdoctoral Fellowship, The Medical Foundation
1992-1993, Postdoctoral Fellowship, American Heart Association
1991-1992, Postdoctoral Fellowship in Advanced Studies in Neurobiology, Keck Center, University of Washington

Previous Positions

2000-2002, Assistant Professor, University of Washington, School of Medicine, Pharmacology
1997-2002, Assistant Professor, University of Washington, Public Health, Environmental Health, Toxicology
1992-1996, Post-doctoral Fellow, Harvard University, Medical School, Neurobiology

Funding Received

  • National Institutes of Health (NIH): Mechanisms of pesticides-induced neuronal apoptosis, 2004 to 2008.
  • National Institutes of Health (NIH): Neuronal Function of JNK, 2002 to 2006.
  • National Institutes of Health (NIH): Regulation and function of ERK5 in CNS neurons, 2001 to 2005.

Publications

  • Xia Z, Storm DR (Apr 2005) The role of calmodulin as a signal integrator for synaptic plasticity., Nature Reviews. Neuroscience, 6 (4), 267-76 Abstract
  • Newhouse K, Hsuan SL, Chang SH, Cai B, Wang Y, Xia Z, Rotenone-induced apoptosis is mediated by p38 and JNK MAP kinases in human dopaminergic SH-SY5Y cells, Toxicological Sciences: An Official Journal of the Society of Toxicology, 79(1), 137-46, May 2004
  • Chang SH, Poser S, Xia Z, A novel role for serum response factor in neuronal survival, The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 24(9), 2277-85, March 2004
  • Caughlan A, Newhouse K, Namgung U, Xia Z, Chlorpyrifos induces apoptosis in rat cortical neurons that is regulated by a balance between p38 and ERK/JNK MAP kinases, Toxicological Sciences: An Official Journal of the Society of Toxicology, 78(1), 125-34, March 2004
  • Liu L, Cavanaugh JE, Wang Y, Sakagami H, Mao Z, Xia Z, ERK5 activation of MEF2-mediated gene expression plays a critical role in BDNF-promoted survival of developing but not mature cortical neurons, Proceedings of the National Academy of Sciences of the United States of America, 100(14), 8532-7, July 2003
  • Poser S, Impey S, Xia Z, Storm DR, Brain-derived neurotrophic factor protection of cortical neurons from serum withdrawal-induced apoptosis is inhibited by cAMP, The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 23(11), 4420-7, June 2003
  • Hetman M, Hsuan SL, Habas A, Higgins MJ, Xia Z, ERK1/2 antagonizes glycogen synthase kinase-3beta-induced apoptosis in cortical neurons, Journal of Biological Chemistry, 277(51), 49577-84, December 2002 Abstract
  • Ghahremani MH, Keramaris E, Shree T, Xia Z, Davis RJ, Flavell R, Slack RS, Park DS, Interaction of the c-Jun/JNK pathway and cyclin-dependent kinases in death of embryonic cortical neurons evoked by DNA damage, Journal of Biological Chemistry, 277(38), 35586-96, September 2002 Abstract
  • Zhu Y, Mao XO, Sun Y, Xia Z, Greenberg DA, p38 Mitogen-activated Protein Kinase Mediates Hypoxic Regulation of Mdm2 and p53 in Neurons, Journal of Biological Chemistry, 277(25), 22909-14, June 2002 Abstract
  • Kornhauser JM, Cowan CW, Shaywitz AJ, Dolmetsch RE, Griffith EC, Hu LS, Haddad C, Xia Z, Greenberg ME, CREB transcriptional activity in neurons is regulated by multiple, calcium-specific phosphorylation events, Neuron, 34(2), 221-33, April 2002 Abstract
  • Xia Z, Storm DR, CaRF: A neuronal transcription factor that CaREs, Neuron, 33(3), 315-6, January 2002
  • Namgung U, Xia Z, Arsenic induces apoptosis in rat cerebellar neurons via activation of JNK3 and p38 MAP kinases, Toxicology and Applied Pharmacology, 174(2), 130-8, 2001 Abstract
  • Cavanaugh, J. E., Ham, J., Hetman, M., Poser, S., Yan, C., and Xia, Z, Differential Regulation of Mitogen Activated Protein Kinases ERK1/2 and ERK5 by Neurotrophins, Neuronal Activity and cAMP in Neurons, Journal of Neuroscience, 21(2), 434-443, 2001
  • Figueroa Masot, X. A., Hetman, M., Higgins, M., Kokot, N., Xia, Z, Differential Role of Bcl-2 Phosphorylation in Paclitaxel (Taxol)-Induced Apoptosis in Post-Mitotic Neurons and Proliferating HEK 293 Cells, Journal of Neuroscience, 21(13), 4657-6, 2001
  • Chan, G. C. K., Lernmark, U., Xia, Z. and Storm D. R, DNA Elements of the Type I Adenylyl Cyclase Gene Locus Enhance Reporter Gene Expression in Neurons and Pinealocytes, European Journal of Neuroscience, 13(11), 2054-2066, 2001
  • Hetman M, Kaleta A, Chlystun M, Higgins M, Cavanaugh J, Xia Z, Glycogen synthase kinase-3?beta as a target for anti-apoptotic signals, 6(2B), 494, 2001
  • Mabuchi, T., Kitagawa, K., Kuwabara, K., Takasawa, K., Ohtsuki,T., Xia, Z., Storm, D., Yanagihara, T., Hori, M., Matsumoto, M, Phopshorylation of CREB in hiipocampal neurons as a protective reponse after exposure to glutamate in vitro and ischemia in vivo, Journal of Neuroscience, 21, 9204-13, 2001
  • Ghatan, S., Larner, S., Kinoshita, Y., Hetman, M., Patel, L., Xia, Z., Youle, R. J., Morrison, R. S, p38 MAP kinase mediates bax translocation in nitric oxide-induced apoptosis in neurons, Journal of Cell Biology, 15(2), 335-F348, 2000
  • Hetman, M., Smith-Cavanaugh, J. E., Kimelman, D. and Xia, Z, Role of Glycogen Synthase Kinase-3ß in Neuronal Apoptosis Induced by Trophic Withdrawal, Journal of Neuroscience, 20(7), 2567-2574, 2000
  • Scott T. Wong, Kien Trinh, Jia Wei, Graeme Lowe, Anuj Gaggar, Zhengui Xia, Geoffrey H. Gold and Daniel R. Storm, Disruption of the Type III Adenylyl Cyclase Gene Leads to Peripheral and Behavioral Anosmia in Transgenic Mice, Neuron, 2000
  • Poser, S., Impey, K., Trinh, K., Xia, Z., and Storm, D. R, SRF-dependent gene expression is required for mitogen-induced proliferation through a PI3 kinase signal transduction cascade, EMBO Journal, 2000
  • Namgung, Uk., and Xia, Z., Arsenite-Induced Apoptosis in Cortical Neurons Is Mediated by JNK3 and p38 MAP Kinases, Journal of Neuroscience, 2000
  • Hetman M, Xia Z, Signaling pathways mediating anti-apoptotic action of neurotrophins, Acta Neurobiologiae Experimentalis, 60(4), 531-45, 2000 Abstract
  • Yue, T. L., J. Niá, A. M Romanic, J. L. Gu, P. Keller, C. Wang, S. Kumar, G. L.Yuá, T. K. HartÜ, X. Wang, Z. Xia, W. E. DeWolf Jr and G. Z. Feuerstein, TL1, a Novel TNF-like Cytokine, Induces Apoptosis in Endothelial Cells: Involvement of Activation of Stress Protein Kinases (SAPK and p38 MAPK) and Caspase-3 Like Protease, Journal of Biological Chemistry, 274, 1479-1486, 1999
  • Hetman, M., Kanning, K., Smith-Cavanaugh, J. E. and Xia, Z, Neuroprotection by Brain-Derived Neurotrophic Factor Is Mediated by Extracellular-Signal-Regulated Kinase and Phosphatidylinositol-3 Kinase, Journal of Biological Chemistry, 274:, 22569-22580, 1999
  • Xing J, Kornhauser J, Xia Z, Thiele E and Greenberg M, Nerve growth factor activates extracellular signal-regulated kinase and p38 mitogen-activated protein kinase pathways to stimulate CREB serine 133 phosphorylation, Molecular and Cellular Biology, 18(4), 1946-1955, 1998
  • Xia Z and Storm D, Calmodulin-regulated adenylyl cyclases and neuromodulation, Curr Opin Neurobio, 7(3), 391-396, 1997
  • Dickens M, Rogers J, Cavanagh J, Raitano A, Xia Z, Halpern J, Greenberg M, Sawyers C and Davis R, A cytoplasmic inhibitor of the JNK signal transduction pathway, Science, 277, 693-696, 1997
  • Xia Z, Dudek H, Miranti C and Greenberg M, Calcium influx via the NMDA receptor induces immediate early gene transcription by a MAP kinase/ERK dependent mechanism, Journal of Neuroscience, 16(17), 5425-5436, 1996
  • Wu Z, Thomas S, Xia Z, Villacres E, Palmiter R and Storm D, Deficient spatial memory and altered LTP in type I adenylyl cyclase mutant mice, Proceedings of the National Academy of Sciences, 92, 220-224, 1995
  • Xia Z, Dickens M, Raingeaud J, Davis R and Greenberg M, Opposing effects of ERK and JNK-p38 MAP Kinases on apoptosis, Science, 270, 1326-1331, 1995
  • Xia Z, Choi E, Wang F, Blazynski C and Storm D, The type I calmodulin sensitive adenylyl cyclases is neural specific, Journal of Neurochemistry, 60, 305-311, 1993
  • Choi E, Xia Z and Storm D, Stimulation of the type III olfactory adenylyl cyclase by calcium and calmodulin, Biochemistry, 31, 6492-6498, 1992
  • Xia Z, Choic E, Wang F and Storm D, The type III calcium/calmodulin sensitive adenylyl cyclase is not specific to olfactory sensory neurons, Neuroscience Letters, 144, 169-173, 1992
  • Xia Z, Refsdal D, Merchant K, Dorsa D and Storm D, Distinct patterns for the distribution of mRNA for the calmodulin-sensitive adenylate cyclase in rat brain: Expression in areas assocated with learning and memory, Neuron, 6, 431-443, 1991
  • Tota M, Xia Z, Storm D and Schimerlik M, Reconstitution of muscarinic receptor mediated inhibition of adenylyl cyclase, Molecular Pharmacology, 37, 950-957, 1990
  • Xia Z and Storm D, A-type ATP binding consensus sequence is critical for the catalytic activity of the calmodulin sensitive adenylate cyclase from bacillus anthracis, Journal of Biological Chemistry, 265, 6517-6520, 1990

Profile Details

Last Updated: 9/19/2007

COS Expertise ID #423597
Reference this profile directly: http://myprofile.cos.com/xiaz2