Keywords: neural stem cell research
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A decade of success
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Dr. Zheng - UNMC's Secret Weapon in China
The Laboratory of Neurotoxicology is currently pursuing several investigative routes to elucidate the mechanism involved in HIV-1 Associated Dementia (HAD). These routes include: neurogenesis, mononuclear phagocyte (MP) activation in the brain, HIV viral proteins and their neurotoxic effects, and the chemokines (chemical signals) released by neurons, astrocytes and MP and their direct consequences on the brain environment. While these areas of research seem miles apart, they are actually quite linked. Studies have shown that neurogenesis plays an important role in the adult brain and can be stimulated by neuronal injury, physical exercise or stress. HIV-infected and activated MP can release viral proteins and neurotoxins, including glutamate, that injure neighboring neurons. Upon injury, neurons release chemokines that recruit more MPs to the site of injury, to repair the injury and promote neurogenesis as well as, rid the site of cellular debris and viral proteins. Infected and activated MP then respond to the signals produced by neurons, releasing more neurotoxins, thereby creating more damage and beginning yet another vicious cycle of injury. Therefore, by integrating studies of neuroscience, virology, immunology, biochemistry and receptor pharmacology to investigate these areas, the neuropathogenesis of HAD can be fully explored
Long Range Goals
The mission of our lab is to ultimately develop drugs that will selectively inhibit neurotoxin production and enhance neuronal repair in the brain. These studies will not only answer questions regarding HAD, but also other neurological diseases such as Alzheimer's disease.
- Xu P, Wang Y, Qin Z, Qiu L, Zhang M, Huang Y, Zheng JC. Combined Medication of Antiretroviral Drugs Tenofovir Disoproxil Fumarate, Emtricitabine, and Raltegravir Reduces Neural Progenitor Cell Proliferation In Vivo and In Vitro. J Neuroimmune Pharmacol. 2017 Dec;12(4):682-692. PMID: 28735382. PMCID: PMC5693968
- Wang K, Ye L, Lu H, Chen H, Zhang Y, Huang Y, Zheng JC. TNF-α promotes extracellular vesicle release in mouse astrocytes through glutaminase. J Neuroinflammation. 2017 Apr 20;14(1):87. PMID: 28427419. PMCID: PMC5399318
- Yang Z, Liu Y, Ahn J, Qiao Z, Endres JL, Gautam N, Huang Y, Li J, Zheng J, Alnouti Y, Bayles KW, Li R. Novel fluorinated pyrrolomycins as potent anti-staphylococcal biofilm agents: Design, synthesis, pharmacokinetics and antibacterial activities. Eur J Med Chem. 2016 Nov 29;124:129-137. PMID: 27565555.
- Tian, C., Tian, C., Liu, Q., Ma, K., Wang, Y., Chen, Q., Ambroz, R., Klinkebiel, D., Li, Y.,Huang, Y., Ding, J., Wu, J. and Zheng, J. (2013). Characterization of Induced Neural Progenitors from Skin Fibroblasts by a Novel Combination of Defined Factors. Scientific Reports. 3:1345. PMID: 23439431
- Zhu, B, Xu, D., Deng, X., Chen, Q., Huang, Y., Peng, P., Li, Y., Jia, B., Wallace B. Thoreson, W.B., Ding, W., Ding, J., Zhao, L., Wang, Y., Wavrin, K.L., Duan, S., Zheng, J. (2012). CXCL12 Enhances Human Neural Progenitor Cells Survival through a CXCR7- and CXCR4-mediated Endocytotic Signaling Pathway. Stem Cells. 30 (11):2571-83. doi: 10.1002/stem.1239. PMID: 22987307. IF: 7.781
- Huang, Y., Zhao, L., Jia, B., Li, Y., Curthoys, N., Zheng, J. (2011) Glutaminase dysregulation in HIV-1-infected human microglia mediates neurotoxicity: relevant to HIV-1 associated neurocognitive disorders. J. Neurosci. 19;31(42):15195-204. PMID: 22016553. Citation: 1; IF: 7.115
- Whitney NP, Eidem TM, Peng H, Huang Y, Zheng JC. (2009) Inflammation mediates varying effects in neurogenesis: relevance to the pathogenesis of brain injury and neurodegenerative disorders. J Neurochem. Mar;108(6):1343-59. PMID: 19154336
- Erdmann N, Tian C, Huang Y, Zhao J, Herek S, Curthoys N, Zheng J. (2009) In vitro glutaminase regulation and mechanisms of glutamate generation in HIV-1-infected macrophage. J Neurochem. Apr;109(2):551-61. PMID: 19222703
- Wu Y, Peng H, Cui M, Whitney NP, Huang Y, Zheng JC. (2009) CXCL12 increases human neural progenitor cell proliferation through Akt-1/FOXO3a signaling pathway. J Neurochem. May; 109(4): 1157–1167. PMID: 19302476
- Huang Y, Walstrom A, Zhang L, Zhao Y, Cui M, Ye L, Zheng JC. (2009) Type I interferons and interferon regulatory factors regulate TNF-related apoptosis-inducing ligand (TRAIL) in HIV-1-infected macrophages. PLoS One. 4(4):e5397. PMID: 19404407
- Tian C, Murrin LC, Zheng JC. Mitochondrial Fragmentation Is Involved in Methamphetamine-Induced Cell Death in Rat Hippocampal Neural Progenitor Cells. PLoS ONE. (2009) 4(5): e5546. PMID: 19436752
Additional publications in PubMed.