Andrew J. Henderson, PhD
Professor
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
Division of Graduate Medical Sciences


Professor
Boston University School of Medicine
Microbiology


Member
Boston University
BU-BMC Cancer Center


Member
Boston University
Evans Center for Interdisciplinary Biomedical Research


Boston Medical Center


Member
Boston University
Genome Science Institute


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



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)
07/22/2019 - 04/30/2024 (Multi-PI)
PI: Andrew J. Henderson, PhD
NIH/Fogarty International Center
1U2RTW011293-01

BU-UL Partnership to Enhance Emerging Epidemic Virus Research in Liberia (BULEEVR)
09/08/2017 - 08/31/2019 (Multi-PI)
PI: Andrew J. Henderson, PhD
NIH/Fogarty International Center
1D71TW010785-01


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)
NIH-NIAID
5R01AI138960-02

Overcoming HIV-1 transcriptional latency in unresponsive CD4 T cells
08/01/2017 - 07/31/2021 (PI)
Univ of Alabama NIH-NIAID
5R01AI122842-03

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

Transcription mechanisms that contribute to HIV-1 Latency
04/01/2013 - 03/31/2019 (PI)
NIH-NIAID
4R01AI097117-04

Transcription mechanisms that contribute to HIV-1 Latency
04/01/2013 - 03/31/2019 (PI)
NIH-NIAID
5R01AI097117-03

Lifespan/Tufts/brown Center for AIDS Research (CFAR): Core H Basic & Translational Sciences
07/01/2016 - 06/30/2018 (PI)
Miriam Hospital NIH-NIAID

Identification of Signals Required for the Establishment of HIV Infection
09/02/2015 - 08/31/2017 (PI)
NIH-NIAID
1R56AI118682-01

Showing 10 of 19 results. Show All Results

Title


Yr Title Project-Sub Proj Pubs
2020 BU PREP 1R25GM125511-01A1
2020 BU-UL Partnership to Enhance Emerging Epidemic Virus Research in Liberia (BULEEVR) 5U2RTW011293-02
2020 Effect of opioid use disorder on HIV latent reservoirs and immune dysfunction assessed by single-cell transcriptomics 5R61DA047032-03 1
2020 Effect of opioid use disorder on HIV latent reservoirs and immune dysfunction assessed by single-cell transcriptomics 3R61DA047032-03S1 1
2020 Signals that establish and maintain HIV latency 5R01AI138960-03 2
2019 BU-UL Partnership to Enhance Emerging Epidemic Virus Research in Liberia (BULEEVR) 1U2RTW011293-01
2019 Effect of opioid use disorder on HIV latent reservoirs and immune dysfunction assessed by single-cell transcriptomics 5R61DA047032-02 1
2019 Single nuclei transcriptomics of Alzheimer's brain disease 3R61DA047032-02S1 1
2019 Signals that establish and maintain HIV latency 5R01AI138960-02 2
2019 Core H - Basic & Translational Sciences 5P30AI042853-21-7399 905
Showing 10 of 39 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.

iCite Analysis       Copy PMIDs To Clipboard

  1. Karagiannis TT, Cleary JP, Gok B, Henderson AJ, Martin NG, Yajima M, Nelson EC, Cheng CS. Single cell transcriptomics reveals opioid usage evokes widespread suppression of antiviral gene program. Nat Commun. 2020 05 26; 11(1):2611. PMID: 32457298
     
  2. He X, Eddy JJ, Jacobson KR, Henderson AJ, Agosto LM. Enhanced HIV-1 Replication in CD4+ T Cells Derived from Individuals with Latent Mycobacterium tuberculosis Infection. J Infect Dis. 2020 May 16.View Related Profiles. PMID: 32417884
     
  3. Olson A, Basukala B, Wong WW, Henderson AJ. Targeting HIV-1 proviral transcription. Curr Opin Virol. 2019 10; 38:89-96. PMID: 31473372
     
  4. 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 05; 15(5):e1007802.View Related Profiles. PMID: 31116788
     
  5. Pedro KD, Henderson AJ, Agosto LM. Mechanisms of HIV-1 cell-to-cell transmission and the establishment of the latent reservoir. Virus Res. 2019 05; 265:115-121.View Related Profiles. PMID: 30905686
     
  6. 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 08 21; 24(8):2088-2100.View Related Profiles. PMID: 30134170
     
  7. 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 08 01; 128(8):3439-3444.View Related Profiles. PMID: 29723162
     
  8. 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
     
  9. 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
     
  10. 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;
     
Showing 10 of 64 results. Show More

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

Bar chart showing 64 publications over 28 distinct years, with a maximum of 6 publications in 2003

YearPublications
19902
19921
19941
19953
19961
19972
19981
20001
20014
20022
20036
20041
20054
20063
20072
20085
20091
20101
20111
20122
20134
20141
20153
20162
20172
20183
20193
20202
In addition to these self-described keywords below, a list of MeSH based concepts is available here.

HIV
kinases
macrophages
RNA polymerase II
signal transduction
T cells
transcription
transcription factors

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  • Diversity Mentor
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Contact for Mentoring:

650 Albany St Evans Biomed Research Ctr
Boston MA 02118
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