Zhigang Xiong M.D. Ph.D.

Associate Scientist
Telephone: 503-413-2086
Fax: 503-413-5465
Email: zxiong@downeurobiology.org

Zhigang Xiong received his M.D. from Anhui Medical University in 1984 and M.Sc. from Sun Yet-Sen University of Medical Science in 1987. He received his Ph.D. from the Department of Pharmacology at the University of Ottawa in 1995 and had his postdoctoral training in the Department of Physiology at the University of Toronto from 1995 to 1999. He joined the Robert S. Dow Neurobiology Laboratories as an assistant scientist in 2000.

Dr. Xiong is a principal investigator and the director of neurophysiology program, leading a research team studying mechanisms of brain injury associated with ischemia and neurotrauma. His research is funded by independent grants from the National Institutes of Health (R01) and the American Heart Association. He is also a co-investigator with Drs. Roger Simon, Julie Saugstad Michael Bottlang, David Greenberg, and Kunlin Jin on five other NIH-funded grants.

Current Lab Staff (As of 8/23/05)

Xiangping Chu, MD, PhD   Senior Research Associate
Weizhen Wang, MD, PhD   Research Associate
Theresa Lusardi, PhD        Research Associate  
Minghua Li, MSc, PhD         Postdoctoral Fellow
Giuseppe Pignataro, PhD  Postdoctoral Fellow
Su-youne Chang, PhD        Postdoctoral Fellow
Jingli Zhang, MD, PhD        Postdoctoral Fellow
Yan Ding, MD, PhD              Postdoctoral Fellow  (pending US visa)
Eric Kratzer, MSc                  PhD student
Jie Jiang, MD, MSc              PhD student  (pending US visa) 
Joshua Seeds, BA, MSc     Research Assistant II
Lisa Force, Pre-Med            Research Student

The lab is currently recruiting new postdoctoral fellows with research experience in electrophysiology and molecular biology.

Research Interests

The main goal of Dr. Xiong's research is to understand the role of ion channels and membrane receptors in ischemic/traumatic brain injury. Brain ischemia initiates various biochemical changes, which favor the activation of various membrane receptors and ion channels. The focus of Dr. Xiong’s lab is on the calcium-permeable ion channels including glutamate receptor-gated channels, acid-sensing ion channels, a newly identified calcium-sensing cation channel, and a potential oxygen free radical-activated channel. It is hypothesized that activation of these channels contributes either directly or indirectly contributes to intracellular calcium overload and excitatory neuronal injury. Using a combination of patch-clamp recordingtechniques, fluorescent calcium imaging, immunocytochemistry, molecular biology chemical analysistechniques, in vitro and in vivo ischemia models, Dr. Xiong’s team investigates the electrophysiological properties, pharmacological profiles, and the pathological roles of these various ion channels in ischemic brain injury.

One major project in Dr. Xiong's laboratory is to study the molecular mechanisms underlying acidosis-mediated ischemic brain injury. During hypoxia/ischemia, increased anaerobic glycolysis due to the lack of blood and oxygen supply leads to lactic acid accumulation, causing a decrease in pH, a phenomenon termed acidosis. Extracellular pH typically falls to 6.5 during ischemia, and it can fall below 6.0 during severe ischemia or under hyperglycemic conditions (for example, in diabetic patients). For many years, acidosis has been known to play an important role in the pathology of neuronal injury. However, the cellular and molecular mechanisms underlying acidosis-induced injury remain hypothetical, multifactorial and vague. Recent studies in Dr. Xiong's lab have demonstrated that activation of newly described acid-sensing ion channels (ASICs), and subsequent calcium entry through these channels are largely responsible for acidosis-induced calcium-dependent neuronal injury. Further studies are under way to test the protective effects of ASIC blockers in whole animal models of brain ischemia, and to test the neuroprotection in animals lacking specific genes encoding these channels. Success of this project may lead to novel and effective therapeutic strategies for stroke patients.

Traumatic brain injury is another major project studied in Dr. Xiong’s laboratory. In a close collaboration with the laboratory of Dr. Michael Bottlang, Director of the Legacy Biomechanics Laboratory, Dr. Xiong’s lab is characterizing a novel in vitro model of traumatic brain injury that subjects organotypic brain slices to rapid angular acceleration induced shear strain. In this model, angular acceleration delivers a scalable, defined, and clinically relevant mechanical insult. Organotypic slices represent three-dimensional brain structure with heterogeneous cell populations in vivo. Assessment of cell injury was performed by measuring the release of lactate dehydrogenase into the slice medium, and by uptake of fluorescent dye propidium iodide. TUNEL staining and Western blot are also used to analyze apoptotic cell death following the traumatic insult. The injury mechanisms and possible neuroprotective interventions are under active investigation.

Dr. Xiong’s lab also collaborates with scientists at the Buck Institute for Age Research on the studies of neurogenesis following ischemic brain injury.

Selected Publications

Xiong ZG, Zhu XM, Chu XP, Minami M, Hey J, Wemmie JA, Price M, Welsh MJ, and Simon RP. Novel Neuroprotective strategy in ischemia: blocking calcium-permeable acid-sensing ion channels. Cell 118(6): 687-98. 2004.

Chu XP, Wemmie JA, Wang WZ, Zhu XM, Saugstad JA, Price MP, Simon RP, Xiong ZG. Subunit-dependent High-Affinity Zinc Inhibition of Acid-Sensing Ion Channels. J. Neurosci. 240(40): 8678-8689, 2004.

Ye JH, Wang FS, Krnjev K, Wang W, Xiong ZG, and Zhang JL. Presynaptic Glycine Receptors on GABAergic Terminals Facilitate Discharge of Dopaminergic Neurons in Ventral Tegmental Area. J. Neurosci. 24(41): 8961-8974, 2004.

Zhou A, Minami M, Zhu X, Bae S, Minthorne J, Lan J, Xiong ZG and Simon RP. Altered Biosynthesis of Neuropeptide Processing Enzyme Carboxypeptidase E after brain ischemia: molecular mechanism and implication. J Cereb Blood Flow Metab. 24(6): 612-22, 2004.

Aarts M, Iihara K, Wei WL, Xiong ZG, Arundine M, Cerwinski W, MacDonald JF, and Tymianski M. A key role for TRPM7 channels in anoxic neuronal death. Cell 115(7): 863-77, 2003.

Chu XP, Zhu XM, Wei WL, Li GH, Simon RP, MacDonald JF, and Xiong ZG. Acidosis decreases low Ca2+-induced neuronal excitation by inhibiting the activity of calcium-sensing cation channels. J Physiol. 550(2):385-399, 2003.

Stenzel-Poore MP, Stevens SL, Xiong ZG, Lessov NS, Harrington CA, Mori M, Meller R, Tobar E, Rosenzweig HL, Shaw TE, Chu XP and Simon RP. Ischemic preconditioning in the brain reprograms the genetic response to cerebral ischemia and mimics neuroprotective strategies found in hibernation. Lancet 362:1028-1037, 2003.

Meller R, Schindler CK, Chu XP, Xiong ZG, Cameron JA, Simon RP and Henshall D. Seizure-like activity leads to the release of BAD from 14-3-3 protein and cell death in hippocampal neurons in vitro. Cell Death & Differentiation. 10:539-47, 2003.

Chu XP, Miesch J, Johnson M, Root L, Zhu XM, Simon RP, Xiong ZG. Proton-gated channels in PC12 cells. J. Neurophysiol. 87(5): 2555-2561, 2002.

Xiong ZG, Chu XP, MacDonald JF. Effect of lomotrigine on the Ca2+-sensing cation channel in cultured hippocampal neurons. J. Neurophysiol. 86(5): 2520-2526, 2001.

Xiong ZG, O'Hanlon D, Becker LE, Roder J, MacDonald JF and Marks A. Decreased calcium-buffering capacity in neonatal cerebellar glia cultures derived from S100B null mice. Exp. Cell Res. 257(2): 281-9, 2000.

Tavern F, Xiong ZG, Roder JC, Salter MW and MacDonald JF. The Lurcher mutation of an AMPA receptor subunit enhances potency of glutamate and converts an antagonist to an agonist. J. Bio. Chem. 275(12): 8475-9, 2000.

Sattler R, Xiong ZG, Lu WY, MacDonald JF and Tymianski M. Distinct role of synaptic and extra-synaptic NMDA receptors in excitotoxicity. J. Neurosci. 20(1):22-33, 2000.

Xiong ZG, Pelkey KA, Lu WY, Lu YM, Roder J, MacDonald JF and Salter MW. Src potentiation of native NMDA receptor function is not through removing zinc inhibition. J. Neurosci. 19:RC37 (1-6), 1999.

Sattler R, Xiong ZG, Lu WY, Hafner M, MacDonald JF and Tymianski M. Specific coupling of NMDA receptor activation to nitric oxide neurotoxicity by PSD-95 protein. Science 284:1845-1848, 1999.

Lu WY, Xiong ZG, Lei SB, Orser BA, Dudek EM, Browing MD and MacDonald JF. G-protein-coupled receptors act via protein kinase C and Src to regulate NMDA receptors. Nature Neurosci. 2(4):331-338, 1999.

Xiong ZG, Raouf R, Lu WY, Lickteig R, Dudek EM, Browing MD, Orser BA and MacDonald JF. Regulation of NMDA receptor function and sensitivity to divalent cations by constitutively active protein kinase C. Mol. Pharmacol. 54 (6): 1055-1063, 1998.

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

Lu WY, Xiong ZG, Orser BA and MacDonald JF. Multiple sites of action of neomycin, Mg2+ and spermine on the NMDA receptors of rat hippocampal CA1 pyramidal neurons. J. Physiol. 512(1): 29-46, 1998.

Xiong ZG, Lu WY and MacDonald JF. Extracellular calcium sensed by a novel cation channel in hippocampal neurons. Proc. Natl. Acad. Sci. USA, 94:7014-7017, 1997.

Jarvis CJ, Xiong ZG, Plant J, Churchill B, Lu WY, MacVicar B, and MacDonald JF. Brain-derived neurotrophic factor (BDNF) potentiates NMDA-evoked responses. J. Neurophysiol. 78:2363-2371, 1997.

Jia ZP, Agopyan N, Miu P, Xiong ZG, Henderson J, Gerlai R, Taverna F, Velumian A, MacDonald JF, Carlen P, Abramow-Newerly W, and Roder J. Enhanced LTP in mice deficient in the AMPA receptor Glu R2. Neuron 17:945-956, 1996.

Valenzuela CV, Xiong ZG, MacDonald JF, Weiner J, Frazier CJ, Dunwiddie TV, Kazlauskas A, Whiting PJ, and Harris RA. Platelet-derived growth factor induces a long-term inhibition of N-Methyl-D-aspartate receptor function. J. Bio. Chem. 271(27): 16151-16159, 1996.

Xiong ZG and Cheung DW. ATP-dependent inhibition of Ca2+-activated K+ channels in vascular smooth muscle cells by neuropeptide Y. Pflugers Arch 431:110-116, 1995.