Zhigang Xiong, MD, PhD
Senior Scientist
Director, Neurophysiology Program
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. He was promoted to Associate Scientist in 2003, and Senior Scientist in 2006.
Dr. Xiong is a principal investigator and the director of the neurophysiology program, leading a research team studying mechanisms of brain injury associated with ischemia and neurotrauma. His research is funded by multiple 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.
Research Team Members (As of 12/12/06)
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
Koichi Inoue, MD, PhD Postdoctoral Fellow
Jie Jiang, MD, MSc Postdoctoral Fellow
Eric Kratzer, MSc PhD student
Joshua Seeds, BA, MSc Research Assistant III
Deborah Branigan, BA Research Assistant II
Jillian Hansen, BA Research Assistant I
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 either directly or indirectly contributes to intracellular calcium overload and excitatory neuronal injury. Using a combination of patch-clamp recordingtechniques, fluorescent calcium imaging, immunocytochemistry, confocal microscopy, molecular biology, 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/traumatic 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 and modulators 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 Key Publications
Xiong ZG, Pignataro G, Li MH, Chang SY and Simon RP.
Acid-sensing ion channels as pharmacological targets for neurodegenerative disease.
Curr Opin Pharmacol. 8(1): 25-32, 2008.
Jiang J, Li MH, Inoue K, Chu XP, Seeds J, Xiong ZG.
TRPM7-like current in human head and neck carcinoma cells: role in cell proliferation.
Cancer Res. 67(22): 10929-38, 2007.
Pignataro G, Simon RP, and Xiong ZG.
Prolonged activation of ASIC1a and the time window for neuroprotection in cerebral ischaemia.
Brain 130(Pt 1): 151-8, 2006
Wang WZ, Chu XP, Li MH, Seeds J, Simon RP, Xiong ZG.
Modulation of acid-sensing ion channel currents, acid-induced increase of intracellular Ca2+, and acidosis-mediated neuronal injury by intracellular pH.
J Biol Chem. 281(39): 29369-78, 2006.
Chu XP, Close N, Saugstad JA, Xiong ZG.
ASIC1a-specific modulation of acid-sensing ion channels in mouse cortical neurons by redox reagents.
J Neurosci. 26(20): 5329-39, 2006.
MacDonald JF, Xiong ZG, Jackson M.
Paradox of Calcium Signaling, Cell Death and Stroke.
Trends in Neurosci. 29(2): 75-81, 2006.
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. S
ubunit-dependent High-Affinity Zinc Inhibition of Acid-Sensing Ion Channels.
J Neurosci. 240 (40): 8678-8689, 2004.
Aarts M, Iihara K, Wei W, Xiong ZG, Arundine M, MacDonald JF and Tymianski M.
A key role for TRPM7 channels in anoxic neuronal death.
Cell 115: 863-877, 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.
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, 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.
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.
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