UNC HIV Cure Center and Department of Biochemistry & Biophysics
PhD – Academy of Military Medical Sciences
Transcription of HIV
HIV-associated neurocognitive disorders (HAND)
HIV latency and HIV cure/remission
Gut health and microbiome
Anti-retroviral therapy (ART) is very effective to suppress HIV-1 replication in the periphery, however, it fails to eradicate HIV-1 reservoirs in patients. The main barrier for a complete HIV cure is the latent HIV-1, hiding inside the immune cells where no or very low level of viral particles are made. This prevents our immune system to recognize and clear the latent HIV reservoirs in patients. The main goal of my laboratory is to discover the molecular mechanisms how HIV-1 achieves its dormant state and to translate our understanding of HIV latency into therapeutic intervention.
Several research programs are undertaking in my lab with a focus of epigenetic regulation of HIV latency, including molecular mechanisms of HIV replication and latency establishment, host-virus interaction, innate immune response to viral infection, and the role of microbiome in the gut health. Extensive in vitro HIV latency models, ex vivo patient latency models, and in vivo patient and rhesus macaque models of AIDS are carried out in my lab. Multiple tools are applied in our studies, including RNA-seq, proteomics, metabolomics, highly sensitive digital droplet PCR and tissue RNA/DNAscope, digital ELISA, and modern and traditional molecular biological and biochemical techniques. We are also very interested in how non-CD4 expression cells in the central nervous system (CNS) get infected by HIV, how the unique interaction among HIV-1, immune cells, vascular cells, and neuron cells contributes to the initial seeding of latent reservoirs in the CNS, and whether we can target the unique viral infection and latency signaling pathways to attack HIV reservoirs in CNS for a cure/remission of HIV-1 infection and HIV-associated neurocognitive disorders (HAND). We have developed multiple experimental tools to attack HIV latency, including latency reversal agents for “Shock and Kill” strategy, such as histone deacetylase inhibitors and ingenol family compounds of protein kinase C agonists, and latency inactivating agents for a potential deep silencing of latent HIV-1. Varieties of clinical and pre-clinical models are being tested to evaluate their potential to eradicate latent HIV reservoirs in vivo. We are actively recruiting postdocs, visiting scholars, and technicians. Rotation graduate students and undergraduate students are welcome to join my lab, located in the UNC HIV Cure Center, for these exciting HIV cure research projects.
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”.
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; 4(7):e126027. PMID: 30944245
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.
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.
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.
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.
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.
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.
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.