Laboratory of Shilpa Buch, Ph.D.
Durham Research Center 8026
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 and 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, Liao K, Niu F, Tripathi A, Tian C, Hu G, Buch S. Engineered extracellular vesicles loaded with miR-124 attenuate cocaine-mediated activation of microglia. Front Cell Dev Biol. 2020;8:573. 2020. doi:10.3389/fcell.2020.00573. PMID: 32850781.
- Tripathi A, Thangaraj A, Chivero ET, Periyasamy P, Burkovetskaya ME, Niu F, Guo ML, Buch S. N-Acetylcysteine reverses antiretroviral-mediated microglial activation by attenuating autophagy-lysosomal dysfunction. Front Neurol. 2020;11:840. doi:10.3389/fneur.2020.00840. eCollection 2020. PMID: 33013619.
- Buch S, Periyasamy P, Thangaraj A, Sil S, Chivero ET, Tripathi A. Opioid-Mediated HIV-1 immunopathogenesis. J Neuroimmune Pharmacol. 2020 Oct 8. doi: 10.1007/s11481-020-09960-5. PMID: 33029670.
- Sil S*, Niu F*, Chivero ET,* Singh S, Periyasamy P, Buch S. Role of inflammasomes in HIV-1 and drug abuse mediated neuroinflammaging. Cells. 2020;9(8):E1857. doi: 3390/cells9081857. PMID: 32784383. *Contributed equally.
- Kutchy NA, Peeples ES, Sil S, Liao K, Chivero ET, Hu G, Buch S. Extracellular Vesicles in viral infections of the nervous system. Viruses. 2020; 28;12(7):700. PMID: 32605316 .
- Thangaraj A, Sil S, Tripathi A, Chivero ET, Periyasamy P, Buch S. Targeting endoplasmic reticulum stress and autophagy as therapeutic approaches for neurological diseases. Int Rev Cell Mol Biol. 2020;350:285-325. doi:10.1016/bs.ircmb.2019.11.001. PMID: 32138902.
- Chivero ET, Ahmad R, Thangaraj A, Periyasamy P, Kumar B, Kroeger E, Feng D, Guo ML, Roy S, Dhawan P, Singh AB, Buch S. Cocaine induces inflammatory gut milieu by compromising the mucosal barrier integrity and altering the gut microbiota colonization. Sci Rep. 2019 Aug 21;9(1):12187. doi: 10.1038/s41598-019-48428-2. PMID: 31434922.
- Tripathi A, Thangaraj A, Chivero ET, Periyasamy P, Callen S, Burkovetskaya ME, Guo ML, Buch S. Antiretroviral-mediated microglial activation involves dysregulated autophagy and lysosomal dysfunction. 2019;8(10):1168. doi:10.3390/cells8101168. PMID: 31569373.
- Thangaraj A, Periyasamy P, Guo ML, Chivero ET, Callen S, Buch S. Mitigation of cocaine-mediated mitochondrial damage, defective mitophagy and microglial activation by superoxide dismutase mimetics. 2020;16(2):289-312. doi:10.1080/15548627.2019.1607686. PMID: 30990365.
- Sil S, Periyasamy P, Thangaraj A, Chivero ET, Buch S. PDGF/PDGFR axis in the neural systems. Mol Aspects Med. 2018;62:63-74. doi:10.1016/j.mam.2018.01.006. PMID: 29409855.