Huangui Xiong, MD, PhD

HUANGUI XIONG, MD, PhD
Professor

Durham Research Center, Room 8013
985880 Nebraska Medical Center
Omaha, NE 68198-5880

Phone: 402-559-5140
E-mail: hxiong@unmc.edu

UNMC Today, May 2, 2011
Meet UNMC Distinguished Scientist Huangui (Hank) Xiong, M.D., Ph.D.

Keywords: voltage-gated K channels, NMDA receptors, synaptic transmission and plasticity, neuroinflammation, neuromodulation, learning and memory, HIV-1-associated neurological disorders

 Hear Dr. Xiong describe his work.

Research Interests

The research focus in the Neurophysiology Laboratory is to study cellular and molecular mechanisms underlying the pathogenesis of neurodegenerative disorders including HIV-1-associated dementia (HAD) and Alzheimer’s disease (AD) and to identify potential target(s) for development of therapeutic strategies.

Specifically, we are interested in the role played by mononuclear phagocytes (MPs, brain macrophages and microglia) in HAD/AD pathogenesis, focusing on how the soluble factors (e.g. cytokines), secreted by HIV-1-infected or beta amyloid (Aβ)-stimulated MPs, alter cellular and synaptic physiology resulting in neural dysfunction and degeneration.

One particular interest is to study how MP secretions influence neuronal voltage-gated K+ (Kv) channels leading to neuronal degeneration and resultant cognitive decline as seen in HAD/AD patients. Studies from other laboratories have shown that neuronal K+ currents decrease during learning and animal mutants with Kv channel dysfunction exhibit learning and memory deficits. We hypothesize that HIV-1-infected or Aβ-stimulated MPs decrease neuronal excitability by enhancing outward K+ current, leading to neuronal dysfunction/degeneration and cognitive impairment. To test this hypothesis, we are studying the effects of MP secretions on neuronal outward K+ current and the protective effects of Kv channel blockers on neurocognitive processes in animal models.

Another particular interest is to examine the role of extrasynaptic NMDA receptors (NMDAR) and their signal transduction pathways in MP-associated neurodegeneration. This study is based on recent observations that the location of NMDARs makes the key difference, survival promoting signals derive from synaptic NMDARs, which consist of predominant NR2A-containing NMDARs (NR2ARs); whereas, a cell-death signal comes from extrasynaptic NMDARs, which contain mostly NR2BRs. We hypothesize that HIV-1-infected or Aβ-stimulated MPs elicit activation of extrasynaptic NR2BRs and their signal transduction pathways affecting neuronal and cognitive function. Our goals are to determine the role played by synaptic and extrasynaptic NMDARs in the pathogenesis of neurodegenerative disorders and to identify the target(s) for therapeutic interventions.

Long-range Goals

The goals of our laboratory are:

• To determine and characterize the role played by voltage-gated K+ channels in the pathogenesis of neurocognitive impairment in HAD/AD and identify potential targets for the development of therapeutic strategies and ;
• To examine and clarify the involvement of synaptic NR2A receptors and extra-synaptic NR2B receptors in HAD/AD pathogenesis and explore therapeutic potential of specific antagonists both
  in vitro and in vivo.

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Representative Publications
Xu CH, Liu J, Chen LN, Liang SD, Fujii N, Tamamura H, Xiong H HIV-1 gp120 enhances outward potassium current via CXCR4 and cAMP-dependent PKA signaling in cultured rat microglia. Glia 2011 (in press)

Zhou Y, Tang H, Liu J, Dong J, Xiong H Chemokine CCL2 modulation of neuronal excitability and synaptic transmission in rat hippocampal slices. J. Neurochem. 116(3):406-14, 2011

Zhang J, Liu J, Katafiasz B, Fox H, Xiong H. HIV-1 gp120-Induced Axonal Injury Detected by Accumulation of β-Amyloid Precursor Protein in Adult Rat Corpus Callosum. J. NeuroImmune Pharmacol., 2011 (in press)

Jing T, Wu L, Borgmann K, Surendran S, Ghorpade A, Liu J, Xiong H. Soluble factors from IL-1β-stimulated astrocytes activate NR1a/NR2B receptors: Implications for HIV-1-induced neurodegeneration. Biochem Biophys Res Commun.12:402(2):241-6 2010 

Rump TJ, Muneer PM, Szlachetka AM, Lamb A, Haorei C, Alikunju S, Xiong H, Keblesh J, Liu J, Zimmerman MC, Jones J, Donohue TM Jr, Persidsky Y, Haorah J. Acetyl-L-carnitine protects neuronal function from alcohol-induced oxidative damage in the brain. Free Radic Biol Med. 2010 Nov 30;49(10):1494-504

Peng F, Yao H, Bai X, Zhu X, Reiner BC, Beazely M, Funa K, Xiong H, Buch S. Platelet-derived growth factor-mediated induction of the synaptic plasticity gene Arc/Arg3.1. J Biol Chem. 2010 Jul 9;285(28):21615-24

Reiner BC, Keblesh JP, Xiong H. Methamphetamine abuse, HIV infection, and neurotoxicity. Int J Physiol Pathophysiol Pharmacol. 2009 September 25; 1(2): 162–179

Kiyota T, Yamamoto M, Xiong H, Lambert MP, Klein WL, Gendelman HE, Ransohoff RM, Ikezu T. CCL2 accelerates microglia-mediated Abeta oligomer formation and progression of neurocognitive dysfunction. PLoS One. 2009; 4(7): e6197

Keblesh JP, Dou H, Gendelman HE, Xiong H. 4-Aminopyridine Improves Spatial Memory in a Murine Model of HIV-1 Encephalitis.J Neuroimmune Pharmacol. 2009 Sep;4(3):317-27.

Tang H, Lu D, Pan R, Qin X, Xiong H, Dong J. Curcumin improves spatial memory impairment induced by human immunodeficiency virus type 1 glycoprotein 120 V3 loop peptide in rats. Life Sci. 85(1-2):1-10, 2009

Gendelman, HE, Ding, SY, Gong, N, Liu, J, Ramirez, S, Persidsky, Y, Wang, T, Volsky, DJ, Xiong, H. Monocyte Chemotactic Protein-1 Regulates Voltage-Gated K+ Channels and Macrophage Transmigration. J. Neuroimmune Pharmcol. 4(1):47-59, 2009

Keblesh J, Hu DH, Xiong H. Voltage-gated Potassium Channels in Human Immunodeficiency Virus Type-1 (HIV-1)-associated Neurocognitive Disorders. J Neuroimmune Pharm. 4(1):60-70, 2009

Xiong H, Chang SL, Buch S, Roy S, Ho WZ. SNIP Members in a Recent International Conference: World Summit of Antivirals. J Neuroimmune Pharm. 4(1):4-6, 2009

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Biographical Information 

Visit Dr. Xiong's laboratory