Welcome to Dr. Huangui Xiong's laboratory
Nawal Boukli, PhD, Universidad Central del Caribe, School of Medicine, Puerto, Rico
Howard Fox, MD, PhD, University of Nebraska Medical Center, Omaha, NE
Howard E. Gendelman, MD, University of Nebraska Medical Center, Omaha, NE
Shilpa Buch, PhD, University of Nebraska Medical Center, Omaha, NE
Nobutaka Fujii, Kyoto University, Japan
James Haorah, PhD, University of Nebraska Medical Center, Omaha, NE
Georgette Kanmogne, PhD, University of Nebraska Medical Center, Omaha, NE
Dr. Hirokazu Tamamura, Tokyo Medical and Dental University, Japan
Dr. Shangdong Liang, Nanchang University, Nanchang, China
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 of particular interests 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 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.
Voltage-gated K Channels, Microglia and HIV Dementia
PI: Xiong, H
This grant proposes to study how HIV-1-infected macrophages alter neuronal voltage-gated K (Kv) channels, leading to neuronal dysfunction and cognitive decline. How the “diseased” neurons affect macrophage secretory activity is another focus of this grant. The goals of the proposed studies are to understand HIV-1-associated channelopathies that cause neuronal dysfunction or death and to find potential ways to reverse and/or prevent HIV-1-induced neuronal damage.
Macrophages, NR2B-containing NMDA Receptors and HIV Dementia
PI: Xiong, H
This proposal investigates how HIV-1-infected mononuclear phagocytes (brain macrophages and microglia) activate neuronal extra-synaptic NR2BRs, leading to neuronal damage and ultimately neurocognitive dysfunction.
Scripps NeuroAIDS Preclinical Studies (SNAPS)
PI: Fox, H; Co-I: Xiong, H
This is a Center grant to provide Administrative and Core Support for scientists investigating NeuroAIDS.
Nanomedicine and NeuroAIDS
PI: Gendelman, H; Co-I: Xiong, H
This research proposes to investigate the biophysiological properties of monocytes and monocyte-derived macrophages that influence cell migration both across the blood-brain barrier and within the brain. The central hypothesis is that changes in ion channel expression in monocytes and macrophages following exposure to virus and immune products influences the cell's ability to change its volume and shape, thus influencing cell migration. Such events are pivotal for macrophages to enter the brain and to secrete the toxins that underlie the neuropathogenesis of HIV-1 associated dementia.
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- Primary cell cultures
- Brain slices
- Western and Northern blots
- Two-electrode voltage clamp of Xenopus oocytes
- Extracellular recording
- Whole-cell patch recordings from cultured neural cells and brain slices
- Single channel recordings from frog oocytes and neuronal cultures
- Animal behavior tests (radial armed water maze)
- ELISA, PCR, RT-PCR