Jianuo Liu, MD, PhD

Jianuo Liu

Research Interests
Representative Publications
Biographical Information

JIANUO LIU, MD, PhD
Assistant Professor

Durham Research Center 8034
985880 Nebraska Medical Center
Omaha, NE  68198-5880

Phone: 402-559-2780
E-mail: jnliu@unmc.edu

Member Huangui Xiong's lab

Keywords: HIV-1 associated neurological disorders 


Research Interests:
 
HIV/AIDS has been a serious global problem with huge social, health, and economic consequences. Currently, approximately 40 million people worldwide are infected with HIV-1 and 20-40% of these patients develop HIV-1-associated neurocognitive disorders (HAND), characterized by a syndrome of progressive cognitive, behavioral, and neurological impairments. Despite the widespread use of antiretroviral therapy (ART), the incidence of HAND continues to have devastating impact on the population. This is mainly due to an incomplete understanding of how HIV infection causes neuronal injury and apoptosis, leading to cognitive disorder. Therefore, my research focus is to study how HIV-1 brain infection alters brain macrophage and microglia functions leading to HIV-1-associated neurocognitive impairments.

 

1: Role of potassium (KV) channels in HIV-1 protein (gp120, Tat)-induced microglia neurotoxicity.  Microglia are the primary immune cells in the central nervous system and activated microglia produce soluble factors leading to neuronal injury. Recently, voltage-gated KV channels have gained attention as promising targets for development of therapeutic strategies. Thus, we use molecular immunology and physiology techniques to explore whether KV channels are involved in HIV-1 protein including gp120 and Tat-induced microglia neuronal toxicity. Our findings implicate that HIV-1 proteins (gp120 and Tat) enhanced microglia KV channel expressions, especially KV1.3, leading to microglia activation and resultant production of neurotoxins and consequent neuronal injury. Enhancement of microglia KV1.3 current is mediated through MAPK pathway including Erk1/2 and p38. Blockage of KV1.3 expression attenuated neurotoxicity induced by gp120- or Tat-activated microglia. These results suggest that KV1.3 channel may be a promising target to a new avenue of therapy for immune and inflammation-mediated neurological disorders.

2: Co-morbid effects of HIV-1 infection and drug abuse. Drug abuse is a major cause of the spread of HIV/AIDS. Studies have shown that the incidence and severity of HIV-associated neurocognitive disorders (HAND) are increased with concomitant use of Meth.  In this study, we are actively pursuing how Meth synergizes with HIV-1 gp120 protein to exacerbate HAND. Our data indicate that Meth and HIV activate microglia resulting in microglia production of neurotoxins and consequent neural injury, suggesting microglia appears to be the intersecting target and effector of the two. In addition, the voltage-gated KV channels are also involved in modulating microglia neurotoxic activity. Specifically, this Meth and HIV act synergistically on microglia is controlled by caspase signal pathway.

Long-term goals:

The long-term goal of my research is to determine and identify potential target(s) for the development of therapeutic strategies that may tackle microglia neurotoxic activity and enhance neuronal function and survival in HIV-1 associated neurocognitive disorders.

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 59(6):997-1007 2011

Xu CH, , 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.

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

Hu D, Liu J, Keblesh J, Xiong H.  Involvement of the 4-aminopyridine-sensitive transient A-type K+ current in macrophage-induced neuronal injury. Eur J Neurosci. 2010 Jan;31(2):214-22.

Additional publications in PubMed

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