Assistant Professor of Biochemistry & Biophysics
Joint appointment with UNC HIV Cure CenterPhD – Academy of Military Medical Sciences
Current antiretroviral therapy (ART) is effective in the suppression of HIV replication but failed to eliminate latent HIV reservoirs. Our lab aims to discover the molecular mechanisms how HIV transcription machinery is regulated during active HIV transcription and during the establishment of latency. The ultimate goal is to translate our understanding of transcription and latency of HIV into therapeutic interventions.
1. Epigenetic regulation of HIV transcription and latency: We recently discovered that a previously unrecognized epigenetic modification called histone crotonylation is involved in an efficient transcription of HIV. The induction of crotonylation disrupted HIV latency. In combination with other latency reversal agents (LRAs), the disruption of HIV latency is highly achieved compared with a single LRA. We are particularly interested whether and how crotonylation of histone and non-histone proteins regulates other signaling pathways to directly modulate HIV transcription or latency.
2. Deep silencing for a functional cure of HIV: We recently established a novel HIV deep latency model in which not only a deep latency of HIV can be induced but also sustained. We are actively investigating the molecular mechanisms underlying the induction and maintenance of deep latency and extending it to patient models to deeply silence HIV proviruses and prevent viral rebound.
3. HIV tissue reservoirs: We are interested in how cells in tissues are infected by HIV, such as CNS, placenta, kidney, GALT and skin. For example, how the unique interaction among HIV, immune cells, vascular cells, and neuron cells contributes to the initial seeding of the latent reservoirs in the CNS, and whether we can target the unique viral infection and latency signaling pathways to attack HIV reservoirs in the CNS, thereby controlling HIV-1 infection and HIV-associated neurocognitive disorders (HAND). We will examine it in HIV-infected rhesus macaques, transgenic HAND mouse model and brain tissues from PLWH.
RECENT PUBLICATIONS (click for Full Publication List)
- Yang H, Li X, Yang X, Lu P, Wang Y, Jiang Z, Pan H, Zhao L, Zhu Y, Khan I, Shen Y, Lu H, Zhang T, Jiang G, Ma Z, Wu H, Zhu H. Dual effects of the novel ingenol derivatives on the acute and latent HIV-1 infections. Antiviral Res. 2019 Sep; 169:104555. doi: 10.1016/j.antiviral.2019.104555. PMID: 31295520.
- Elsheikh MM, Tang Y, Li D, and Jiang G*, Deep latency: A new insight into a functional cure of HIV, EBioMedicine, 2019 Jul;45:624-629. doi: 10.1016/j.ebiom.2019.06.020 (*, corresponding author).
- Crakes KR, Jiang G*. Gut microbiome alterations during HIV/SIV infection: Implications for HIV Cure. Front. Microbiol, 22 May 2019 | https://doi.org/10.3389/fmicb.2019.01104 (*, corresponding author).
- Jiang G, Maverakis E, Cheng MY, Elsheikh ME, Deleage C, Méndez-Lagares G, Shimoda M, Yukl SA, Hartigan-O’Connor DJ, Thompson GR III, Estes JD, Wong JK and Dandekar S, Disruption of latent HIV in vivo during the clearance of actinic keratosis by ingenol mebutate. JCI Insight, 2019, accepted and in press.
- Santos Rocha C, Hirao LA, Weber MG, Méndez-Lagares G, Chang WLW, Jiang G, Deere JD, Sparger EE, Roberts J, Barry PA, Hartigan-O’Connor DJ, Dandekar S. Subclinical cytomegalovirus infection associates with altered host immunity, gut microbiota and vaccine responses. J Virol, 2018 Apr 18. pii: JVI.00167-18. doi: 10.1128/JVI.00167-18. (Article in the Cover page and highlighted by the JVI journal. Reported by ScienceDaily)
- Tang Y, George AM, Petrechko O, Nouvet FJ, Sweet SD, Tanaka Y, Imbiakha BS, Jiang G, Gao W, Anastos K, Hildreth JEK. Pseudotyping of HIV-1 with Human T-Lymphotropic Virus 1 (HTLV-1) Envelope Glycoprotein during HIV-1-HTLV-1 Coinfection Facilitates Direct HIV-1 Infection of Female Genital Epithelial Cells: Implications for Sexual Transmission of HIV-1. mSphere, 2018 Apr 4;3(2). pii: e00038-18. doi: 10.1128/mSphere.00038-18.
- Jiang G, Nguyen D, Archin NM, Yukl, SA, Méndez-Lagares G, Tang Y, Elsheikh MM, Thompson GR 3rd, Hartigan-O’Connor, DJ, Margolis DM, Wong JK, Dandekar S. HIV latency is reversed by ACSS2-driven histone crotonylation. J Clin Invest, 2018 Feb 19. pii: 98071. doi: 10.1172/JCI98071. (Reported by media, interviewed by iHeartRadio and by UC-Davis student newspaper The Aggie)
- Jiang G, Santos Rocha C, Hirao LA, Mendes EA, Tang Y, Thompson GR 3rd, Wong JK, Dandekar S. HIV exploits anti-viral host innate GCN2-ATF4 signaling for establishing viral replication early in infection. mBio, 2017 May 2;8(3). pii: e01518-16. doi: 10.1128/mBio.01518-16.
- Glavan TW, Gaulke CA, Santos Rocha C, Sankaran-Walters S, Hirao LA, Raffatellu M, Jiang G, Bäumler AJ, Goulart LR, Dandekar S. Gut mucosal dysfunction through impaired pattern recognition receptor expression and gut microbiota changes in chronic SIV infection. Mucosal Immunol. 2015 Sep 16. doi: 10.1038/mi.2015.92.
- Jiang G, Mendes EA, Kaiser P, Tang Y, Cai I, Melcher GP, Thompson GR 3rd, James E.K. Hildreth, Wong JK, Dandekar S. Synergistic reactivation of latent HIV expression by Ingenol-3-angelate, PEP005, targeted NF-kB signaling in combination with JQ1 induced p-TEFb activation. PLoS Pathogens | DOI:10.1371/journal.ppat.1005066 July 30, 2015. (A Faculty 1000 article and a featured research article with a Press Release by PLoS Pathogens and was reported by many news agencies around the world as a major advance for HIV Cure study, including BBC, VOA, Sacramento Bee. Selected by PLoS Pathogens as one of the most impactful papers in HIV/AIDS to celebrate 2015 World AIDS Day)
- Jiang G, Dandekar S. Targeting NF-κB Signaling with Protein Kinase C Agonists As an Emerging Strategy for Combating HIV Latency. AIDS Res Hum Retroviruses. 2015 Jan;31(1):4-12. doi: 10.1089/AID.2014.0199. PMID: 25287643. (An invited review article by a Special Issue of HIV Cure of the journal and was highlighted in the press release by the journal. Selected by AIDS Res Hum Retroviruses as one of the most important articles published in 2015 to celebrate 2015 World AIDS Day)
- Jiang G, Mendes EA, Kaiser P, Sankaran-Walters S, Tang Y, Weber MG, Melcher GP, Thompson GR 3rd, Tanuri A, Pianowski LF, Wong JK, Dandekar S. Reactivation of HIV latency by a newly modified Ingenol derivative via protein kinase Cδ-NF-κB signaling. AIDS. 2014 May 6. PMID: 24804860. (A Faculty 1000 article and among one of the only seven articles selected from published papers in AIDS journal (from 2013-2015) into IAS 2015 Conference Collection& Webcasts on the theme of HIV Cure by the IAS 2015 meeting)
- Gaulke CA, Porter M, Han YH, Sankaran-Walters S, Grishina I, George MD, Dang AT, Ding SW, Jiang G, Korf I, Dandekar S. Intestinal Epithelial Barrier Disruption through Altered Mucosal MicroRNA Expression in Human Immunodeficiency Virus and Simian Immunodeficiency Virus Infections. J Virol. 2014 Jun;88(11):6268-80. doi: 10.1128/JVI.00097-14. PMID: 24672033.
- Bhaskara S, Knutson SK, Jiang G, Chandrasekharan MB, Wilson AJ, Zheng S, Yenamandra A, Locke K, Yuan JL, Bonine-Summers AR, Wells CE, Kaiser JF, Washington MK, Zhao Z, Wagner FF, Sun ZW, Xia F, Holson EB, Khabele D, Hiebert SW. Hdac3 is essential for the maintenance of chromatin structure and genome stability. Cancer Cell. 2010 Nov 16;18(5):436-47. doi: 10.1016/j.ccr.2010.10.022. PMID: 21075309. (Highlighted by the Cancer Cell journal and reported by lots of media)
- 12. Yang ES*, Wang H*, Jiang G, Nowsheen S, Fu A, Hallahan DE, Xia F. Lithium-mediated protection of hippocampal cells involves enhancement of DNA-PK-dependent repair in mice. J Clin Invest. 2009 May;119(5):1124-35. PMID: 19425167 (* equal contribution).
- Jiang G, Espeseth A, Hazuda DJ, Margolis DM. c-Myc and Sp1 contribute to proviral latency by recruiting histone deacetylase 1 to the human immunodeficiency virus type 1 promoter. J Virol. 2007 Oct;81(20):10914-23. PMID: 17670825.
- Jiang G, Sancar A. Recruitment of DNA damage checkpoint proteins to damage in transcribed and nontranscribed sequences. Mol Cell Biol. 2006 Jan;26(1):39-49. PMID: 16354678.
Books and Chapters:
Guochun Jiang, Shailesh Choudhary, and David M. Margolis. Nov, 2007. “Molecular mechanisms of persistent proviral HIV-1 infection.” in “Persistent and Latent Infection by HIV-1 and Related Lentiviruses, 2007: ISBN: 978-308-0189-6 Editor: Amanda Brown”.
Guochun Jiang and Satya Dandekar, “Disruption of HIV Latency by PEP005 (Ingenol-3-Angelate) Alone or Combined with other Anti-HIV Latency Agents”, Publication No. WO2016022358 A1.
Guochun Jiang and Satya Dandekar, “HIV and latent virus eradication by epigenetic regulation of histone crotonylation” (In pending).
120 Mason Farm Road, CB# 7042
2111 Genetic Medicine Building
Chapel Hill, NC 27599
Phone: 919- 445-0384