Andrew J. Henderson, PhD
Boston University School of Medicine
Dept of Medicine
Infectious Diseases

PhD, University of California, Riverside
MS, University of California, Riverside

My research focuses on cellular mechanisms that regulate HIV replication and transcription. Active projects in the lab include elucidating T cell costimulatory signal transduction cascades that positively and negatively regulate HIV transcription, determining mechanisms by which HIV circumvents anti-inflammatory signals to promote HIV replication and AIDS-associated inflammatory diseases and characterizing the transcriptional status of HIV provirus in T cell and macrophage subsets. Although, HIV is our primary experimental system, our research provides general insights into signal transduction, tissue-specific gene expression, immune cell function and mechanisms that contribute to inflammatory disorders and autoimmunity. Below highlights some of the current on-going projects in the lab:

T cell signals regulate HIV replication. T cell activation through the T cell receptor and costimulatory molecules, including CD28, influences susceptibility of T cells to HIV infection as well as proviral transcription. Incomplete T cell receptor signaling has been proposed to be a mechanism that contributes to proviral latency. We hypothesize that CD28 engagement results in distinct signaling cascades that have very different consequences for HIV transcription. We are actively characterizing signaling events emanating from critical tyrosine residues within the cytoplasmic tail of CD28 that either inhibit or induce HIV transcription to fully appreciate how costimulatory signals impact HIV transcription. In addition, we are characterizing the transcriptional machinery that regulates HIV expression in response to T cell signals. Understanding mechanisms by which CD28 regulates HIV transcription will further define pathways associated with this receptor as well as identify putative upstream signal transduction events critical for controlling HIV expression.

Related projects have suggested that non-receptor tyrosine kinases necessary for T cell activation and function, such as the Src kinase Lck and the Tec kinase Itk mediate efficient release of HIV. The mechanisms by which these kinases influence these late steps of HIV virus replication are actively being studied.

Regulation of HIV transcription elongation. HIV provirus is regulated at the level of transcription and involves changes in transcription initiation, chromatin organization and elongation. In particular, transcription elongation has been demonstrated to be a limiting step for HIV expression and overcoming this block is the primary activity of the viral factor Tat, which through the recruitment of P-TEFb to the LTR, post-translationally modifies RNA polymerase II and associated factors to increase processive transcription. Whether this initial lack of RNA polymerase II processivity represents proximal paused RNA polymerase II, premature termination, or both has not been resolved. Recent work from our lab shows that negative elongation factor NELF and the transcription termination factor Pcf11 repress HIV transcription. We hypothesize that the coordinate control of RNA Polymerase II activity and premature transcription termination coupled with chromatin changes create key check-points for HIV transcription that directly contributes to proviral transcriptional latency. In addition, we posit that there are cellular signals that extinguish HIV expression by inducing promoter proximal pausing and premature termination. Using a receptor tyrosine kinase that represses HIV expression, we are mapping signaling pathways that are upstream of transcription initiation, elongation and termination. Understanding the regulation of HIV transcription elongation will provide novel cellular targets for controlling and purging HIV in different cellular reservoirs.

Assistant Dean
Boston University School of Medicine, Graduate Medical Sciences

Associate Professor
Boston University School of Medicine

Graduate Faculty (Primary Mentor of Grad Students)
Boston University School of Medicine, Graduate Medical Sciences

Boston Medical Center

2011 Journal of Immunology: Associate Editor
2008 Nature Publishing Group, Boston SciCafe: Award for Outstanding Research Achievement
1995-1998 Leukemia Society of America, Special Fellow
1992-1995 The Aaron Diamond Foundation Postdoctoral Research Fellowship
1990 Chancellor’s Patent Fund
1990 Biomedical Sciences Graduate Student Research Award
1987 Newell Graduate Research Award
1986 Newell Graduate Research Award

BU-UL Partnership to Enhance Emerging Epidemic Virus Research in Liberia (BULEEVR)
09/08/2017 - 08/31/2019 (Co-PI)
PI: Nahid Bhadelia, MD, MA
NIH/Fogarty International Center

Providence/Boston Center for AIDS Research(CFAR): Core A-Administrative
07/01/2018 - 06/30/2023 (PI)
Miriam Hospital NIH-NIAID

Providence/Boston Center for AIDS Research(CFAR): Core H-Basic Sciences
07/01/2018 - 06/30/2023 (PI)
Miriam Hospital NIH-NIAID

Signals that establish and maintain HIV latency
05/08/2018 - 04/30/2023 (PI)

Overcoming HIV-1 transcriptional latency in unresponsive CD4 T cells
08/01/2017 - 07/31/2021 (PI)
Univ of Alabama NIH-NIAID

Effect of opioid use disorder on HIV latent reservoirs and immune dysfunction assessed by single…
08/15/2018 - 05/31/2021 (PI)
Trustees of Boston University NIH-NIDA

Disabling HIV provirus by promoting Chromatinization
07/01/2017 - 06/30/2019 (PI)
American Foundation for AIDS Research

Lifespan/Tufts/brown Center for AIDS Research (CFAR): Core H Basic & Translational Sciences
07/01/2016 - 06/30/2019 (PI)
Miriam Hospital NIH-NIAID

Transcription mechanisms that contribute to HIV-1 Latency
04/01/2013 - 03/31/2019 (PI)

Transcription mechanisms that contribute to HIV-1 Latency
04/01/2013 - 03/31/2019 (PI)

Identification of Signals Required for the Establishment of HIV Infection
09/02/2015 - 08/31/2017 (PI)

Showing 10 of 19 results. Show All Results

Yr Title Project-Sub Proj Pubs
2019 Signals that establish and maintain HIV latency 5R01AI138960-02
2018 Effect of opioid use disorder on HIV latent reservoirs and immune dysfunction assessed by single-cell transcriptomics 1R61DA047032-01
2018 Signals that establish and maintain HIV latency 1R01AI138960-01A1
2018 Core H - Basic & Translational Sciences 2P30AI042853-20A1-7399 821
2017 BU-UL Partnership to Enhance Emerging Epidemic Virus Research in Liberia (BULEEVR) 1D71TW010785-01
2016 Transcription mechanisms that contribute to HIV-1 latency 4R01AI097117-04 9
2015 Identification of Signals Required for the Establishment of HIV Infection and Latency 1R56AI118682-01 5
2015 Novel compounds that target HIV latency 5R21AI108447-02 4
2015 Transcription mechanisms that contribute to HIV-1 latency 5R01AI097117-03 9
2014 Novel compounds that target HIV latency 1R21AI108447-01A1 4
Showing 10 of 30 results. Show All Results
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.

  1. Gagne M, Michaels D, Schiralli Lester GM, Gummuluru S, Wong WW, Henderson AJ. Strength of T cell signaling regulates HIV-1 replication and establishment of latency. PLoS Pathog. 2019 May; 15(5):e1007802.View Related Profiles. PMID: 31116788.
  2. Pedro KD, Henderson AJ, Agosto LM. Mechanisms of HIV-1 cell-to-cell transmission and the establishment of the latent reservoir. Virus Res. 2019 May; 265:115-121.View Related Profiles. PMID: 30905686.
  3. Agosto LM, Herring MB, Mothes W, Henderson AJ. HIV-1-Infected CD4+ T Cells Facilitate Latent Infection of Resting CD4+ T Cells through Cell-Cell Contact. Cell Rep. 2018 Aug 21; 24(8):2088-2100.View Related Profiles. PMID: 30134170.
  4. Pena-Cruz V, Agosto LM, Akiyama H, Olson A, Moreau Y, Larrieux JR, Henderson A, Gummuluru S, Sagar M. HIV-1 replicates and persists in vaginal epithelial dendritic cells. J Clin Invest. 2018 Aug 01; 128(8):3439-3444.View Related Profiles. PMID: 29723162.
  5. Agosto LM, Henderson AJ. CD4+ T Cell Subsets and Pathways to HIV Latency. AIDS Res Hum Retroviruses. 2018 09; 34(9):780-789.View Related Profiles. PMID: 29869531.
  6. Graci JD, Michaels D, Chen G, Schiralli Lester GM, Nodder S, Weetall M, Karp GM, Gu Z, Colacino JM, Henderson AJ. Identification of benzazole compounds that induce HIV-1 transcription. PLoS One. 2017; 12(6):e0179100.View Related Profiles. PMID: 28658263.
  7. Miller CM, Akiyama H, Agosto LM, Emery A, Ettinger CR, Swanstrom RI, Henderson AJ, Gummuluru S. Virion-Associated Vpr Alleviates a Postintegration Block to HIV-1 Infection of Dendritic Cells. J Virol. 2017 Jul 01; 91(13).View Related Profiles. PMID: 28424288; DOI: 10.1128/JVI.00051-17;.
  8. Agosto LM, Hirnet JB, Michaels DH, Shaik-Dasthagirisaheb YB, Gibson FC, Viglianti G, Henderson AJ. Porphyromonas gingivalis-mediated signaling through TLR4 mediates persistent HIV infection of primary macrophages. Virology. 2016 Dec; 499:72-81.View Related Profiles. PMID: 27639573; DOI: 10.1016/j.virol.2016.09.007;.
  9. Papadopoulos G, Shaik-Dasthagirisaheb YB, Huang N, Viglianti GA, Henderson AJ, Kantarci A, Gibson FC. Immunologic environment influences macrophage response to Porphyromonas gingivalis. Mol Oral Microbiol. 2017 Jun; 32(3):250-261.View Related Profiles. PMID: 27346827; DOI: 10.1111/omi.12168;.
  10. Agosto LM, Gagne M, Henderson AJ. Impact of Chromatin on HIV Replication. Genes (Basel). 2015; 6(4):957-76.View Related Profiles. PMID: 26437430; DOI: 10.3390/genes6040957;.
Showing 10 of 61 results. Show More

This graph shows the total number of publications by year, by first, middle/unknown, or last author.

Bar chart showing 61 publications over 27 distinct years, with a maximum of 6 publications in 2003

In addition to these self-described keywords below, a list of MeSH based concepts is available here.

RNA polymerase II
signal transduction
T cells
transcription factors

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Contact for Mentoring:

650 Albany St Evans Biomed Research Ctr
Boston MA 02118
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