Laboratory of Shilpa Buch, Ph.D.
Durham Research Center 8024
985880 University of Nebraska Medical Center
Omaha, NE 68198-5880
Keywords: NLRP3 Inflammasome; microglia; neuroinflammation; HIV-1 Tat; drug abuse
Ernest Chivero, Ph.D., receives Rex Montgomery Award for outstanding dissertation. https://www.unmc.edu/news.cfm?match=20259&pk_campaign=email&pk_kwd=UNMC_for_the_record.
University of Iowa: Prize-Winning Researchers (including Ernest Chivero) https://www.grad.uiowa.edu/prize-winning-researchers.
Interview on “HIV: Fighting virus with virus”. University of Iowa 2012-2013 Year-in-Review Article http://www.grad.uiowa.edu/annual-report/2013/ernest-chivero.
My research focuses on understanding molecular mechanisms underlying inflammasome activation and dysfunction in the brain following drug and HIV exposure. The NLRP3 inflammasome has been implicated in HIV-induced microglial activation, which may likely contribute to the development of HIV-associated neurological disorders. The goal of my work is to elucidate how HIV-1 viral proteins and drugs of abuse together exacerbate microglial activation contributing to neuroinflammation via NLRP3 inflammasome activation. These studies will identify NLRP3 inflammasome pathway targets that could be developed as therapeutic interventions to alleviate or prevent neuroinflammation and subsequent cognitive impairment in HIV positive individuals.
- We are currently working on a project to examine the role of the NLRP3 inflammasome in HIV Tat and cocaine-mediated activation of microglia and implications in exacerbated neuroinflammation and neuropathic pain. Substance abuse is increasing; up to 30% of HIV positive people have a co-morbidity with substance abuse such as cocaine or opioids. Thus, understanding the contribution of substance abuse to chronic inflammation observed in HIV positive people is a critical step towards adjunctive therapy.
- We are exploring the role of substance abuse of cocaine in gut innate immune activation and microbiome alterations. Drug use of cocaine is associated with altered metabolism and immune activation that may modify the composition of the intestinal flora. Uncovering the role of drug abuse in gut dysbiosis and immune activation will shed light on chronic inflammation and altered gut-brain communication.
- Harvesting of gut & brain organs/tissue RNA and DNA isolation
- Immunofluorescence microscopy
- Flow cytometry
- Cell culture (primary cells and cell lines)
- Western blots
- Traditional PCRs and Real-Time PCR
- Chivero ET*, Guo M*, Periyasamy P, Liao K, Callen SE and Buch S. HIV Tat primes and activates microglial NLRP3 inflammasome-mediated neuroinflammation. J Neurosci. 2017 Mar 7. pii: 3045-16. doi: 10.1523/JNEUROSCI.3045-16.2017. PMID:28270571.
- Buch S, Chivero ET, Hoare J, Jumare J, Nakasujja N, Mudenda V, Paul R, Kanmogne GD, Sacktor N, Wood C, Royal W, Joseph J. Proceedings from the NIMH symposium on "NeuroAIDS in Africa: neurological and neuropsychiatric complications of HIV". J Neurovirol. 2016 Oct;22(5):699-702. PMID:27473196.
- Chivero ET, Bhattarai N, McLinden JH, Xiang J, Stapleton JT. Human Pegivirus (HPgV; formerly known as GBV-C) inhibits IL-12 dependent natural killer cell function. Virology. 2015 Nov;485:116-27. doi: 10.1016/j.virol.2015.07.008. PMID: 26245365.
- Chivero ET, Stapleton JT. Tropism of Human Pegivirus (formerly known as GB virus C/Hepatitis G virus) and host immunomodulation: insights into a highly successful viral infection. J Gen Virol. 2015 Feb 9: vir.0.000086. doi: 10.1099/vir.0.000086. PMID: 25667328.
- Stapleton JT, Xiang J, McLinden JH, Bhattarai N, Chivero ET, Klinzman D, Kaufman TM, Chang Q. A novel T cell evasion mechanism in persistent RNA virus infection. Trans Am Clin Climatol Assoc. 2014;125:14-24. PMID: 25125715.
- Chivero ET, Bhattarai N, Rydze RT, Winters MA, Holodniy M, Stapleton JT. Human Pegivirus RNA is found in multiple blood mononuclear cells in vivo and serum-derived viral RNA containing particles are infectious in vitro. J Gen Virol. 2014 Jun; 95(Pt 6):1307-19. doi: 10.1099/vir.0.063016-0. PMID: 24668525.
- Bhattarai N, McLinden JH, Xiang J, Landay AL, Chivero ET, Stapleton JT. GB virus C particles inhibit T cell activation via envelope E2 protein-mediated inhibition of TCR signaling. J Immunol. 2013 Jun 15;190 (12):6351-9. doi: 10.4049/jimmunol.1300589. Epub 2013 May 17. PubMed PMID: 23686495; PMCID: PMC3965330.
- Bhattarai N, Rydze RT, Chivero ET, Stapleton JT. GB virus C viremia is associated with higher levels of double-negative T cells and lower T-cell activation in HIV-infected individuals receiving antiretroviral therapy. J Infect Dis. 2012 Nov; 206 (9):1469-72. doi: 10.1093/infdis/jis515. Epub 2012 Aug 20. PubMed PMID: 22927453; PubMed Central PMCID: PMC3466998.
- Brown GD, Meintjes G, Kolls JK, Gray C, Horsnell W; Working Group from the EMBO-AIDS Related Mycoses Workshop, Achan B, Alber G, Aloisi M, Armstrong-James D, Beale M, Bicanic T, Black J, Bohjanen P, Botes A, Boulware DR, Brown G, Bunjun R, Carr W, Casadevall A, Chang C, Chivero E, Corcoran C, Cross A, Dawood H, Day J, De Bernardis F, De Jager V, De Repentigny L, Denning D, Eschke M, Finkelman M, Govender N, Gow N, Graham L, Gryschek R, Hammond-Aryee K, Harrison T, Heard N, Hill M, Hoving JC, Janoff E, Jarvis J, Kayuni S, King K, Kolls J, Kullberg BJ, Lalloo DG, Letang E, Levitz S, Limper A, Longley N, Machiridza TR, Mahabeer Y, Martinsons N, Meiring S, Meya D, Miller R, Molloy S, Morris L, Mukaremera L, Musubire AK, Muzoora C, Nair A, Nakiwala Kimbowa J, Netea M, Nielsen K, O'hern J, Okurut S, Parker A, Patterson T, Pennap G, Perfect J, Prinsloo C, Rhein J, Rolfes MA, Samuel C, Schutz C, Scriven J, Sebolai OM, Sojane K, Sriruttan C, Stead D, Steyn A, Thawer NK, Thienemann F, Von Hohenberg M, Vreulink JM, Wessels J, Wood K, Yang YL. AIDS-related mycoses: the way forward. Trends Microbiol. 2014 Mar; 22(3):107-9. doi: 10.1016/j.tim.2013.12.008. PMID: 24581941.
- Chivero ET, Mutukumira AN, Zvauya R. Partial purification and characterization of a xylanase enzyme produced by a micro-organism isolated from selected indigenous fruits of Zimbabwe. Food Chemistry. 72, 2001. pp 179-185.