Keywords
Last Name

Andrew J. Henderson, PhD

TitleAssociate Professor
InstitutionBoston University School of Medicine
DepartmentMedicine
DivisionInfectious Diseases
Address650 Albany St Evans Biomed Research Ctr
Boston MA 02118
Phone(617) 414-5240
ORCID ORCID Icon0000-0002-9299-5302
Other Positions
TitleAssistant Dean
InstitutionBoston University School of Medicine, Division of Graduate Medical Sciences

TitleGraduate Faculty (Primary Mentor of Grad Students)
InstitutionBoston University School of Medicine, Division of Graduate Medical Sciences

TitleAssociate Professor
InstitutionBoston University School of Medicine
DepartmentMicrobiology

InstitutionBoston Medical Center

 Research Expertise & Professional Interests
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.

 Self-Described Keywords
  • HIV
  • kinases
  • macrophages
  • RNA polymerase II
  • signal transduction
  • T cells
  • transcription
  • transcription factors
 Publications
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.
List All   |   Timeline
  1. 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. PMID: 27639573.
    View in: PubMed
  2. 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. 2016 Jun 27. PMID: 27346827.
    View in: PubMed
  3. Agosto LM, Gagne M, Henderson AJ. Impact of Chromatin on HIV Replication. Genes (Basel). 2015; 6(4):957-76. PMID: 26437430.
    View in: PubMed
  4. Kaczmarek Michaels K, Wolschendorf F, Schiralli Lester GM, Natarajan M, Kutsch O, Henderson AJ. RNAP II processivity is a limiting step for HIV-1 transcription independent of orientation to and activity of endogenous neighboring promoters. Virology. 2015 Dec; 486:7-14. PMID: 26379089.
    View in: PubMed
  5. Kaczmarek Michaels K, Natarajan M, Euler Z, Alter G, Viglianti G, Henderson AJ. Blimp-1, an intrinsic factor that represses HIV-1 proviral transcription in memory CD4+ T cells. J Immunol. 2015 Apr 1; 194(7):3267-74. PMID: 25710909.
    View in: PubMed
  6. Collins MH, Henderson AJ. Transcriptional regulation and T cell exhaustion. Curr Opin HIV AIDS. 2014 Sep; 9(5):459-63. PMID: 25010896.
    View in: PubMed
  7. Kaczmarek K, Morales A, Henderson AJ. T Cell Transcription Factors and Their Impact on HIV Expression. Virology (Auckl). 2013 Sep 24; 2013(4):41-47. PMID: 24436634.
    View in: PubMed
  8. Cary DC, Clements JE, Henderson AJ. RON receptor tyrosine kinase, a negative regulator of inflammation, is decreased during simian immunodeficiency virus-associated central nervous system disease. J Immunol. 2013 Oct 15; 191(8):4280-7. PMID: 24043899.
    View in: PubMed
  9. Natarajan M, Schiralli Lester GM, Lee C, Missra A, Wasserman GA, Steffen M, Gilmour DS, Henderson AJ. Negative elongation factor (NELF) coordinates RNA polymerase II pausing, premature termination, and chromatin remodeling to regulate HIV transcription. J Biol Chem. 2013 Sep 6; 288(36):25995-6003. PMID: 23884411.
    View in: PubMed
  10. Katarzyna Kaczmarek, Ayana Morales and Andrew J. Henderson. T Cell Transcription Factors and Their Impact on HIV Expression. Virology: Research and Treatment. 2013; 4:41-47.
  11. Schiralli Lester GM, Akiyama H, Evans E, Singh J, Gummuluru S, Henderson AJ. Interleukin 2-inducible T cell kinase (ITK) facilitates efficient egress of HIV-1 by coordinating Gag distribution and actin organization. Virology. 2013 Feb 5; 436(1):235-43. PMID: 23260110.
    View in: PubMed
  12. Schiralli Lester GM, Henderson AJ. Mechanisms of HIV Transcriptional Regulation and Their Contribution to Latency. Mol Biol Int. 2012; 2012:614120. PMID: 22701796.
    View in: PubMed
  13. Narayan V, Ravindra KC, Chiaro C, Cary D, Aggarwal BB, Henderson AJ, Prabhu KS. Celastrol inhibits Tat-mediated human immunodeficiency virus (HIV) transcription and replication. J Mol Biol. 2011 Jul 29; 410(5):972-83. PMID: 21763500.
    View in: PubMed
  14. Natarajan M, August A, Henderson AJ. Combinatorial signals from CD28 differentially regulate human immunodeficiency virus transcription in T cells. J Biol Chem. 2010 Jun 4; 285(23):17338-47. PMID: 20368329.
    View in: PubMed
  15. Kalantari P, Narayan V, Henderson AJ, Prabhu KS. 15-Deoxy-Delta12,14-prostaglandin J2 inhibits HIV-1 transactivating protein, Tat, through covalent modification. FASEB J. 2009 Aug; 23(8):2366-73. PMID: 19299483.
    View in: PubMed
  16. Kalantari P, Narayan V, Natarajan SK, Muralidhar K, Gandhi UH, Vunta H, Henderson AJ, Prabhu KS. Thioredoxin reductase-1 negatively regulates HIV-1 transactivating protein Tat-dependent transcription in human macrophages. J Biol Chem. 2008 Nov 28; 283(48):33183-90. PMID: 18835810.
    View in: PubMed
  17. Strasner AB, Natarajan M, Doman T, Key D, August A, Henderson AJ. The Src kinase Lck facilitates assembly of HIV-1 at the plasma membrane. J Immunol. 2008 Sep 1; 181(5):3706-13. PMID: 18714047.
    View in: PubMed
  18. Kalantari P, Harandi OF, Hankey PA, Henderson AJ. HIV-1 Tat mediates degradation of RON receptor tyrosine kinase, a regulator of inflammation. J Immunol. 2008 Jul 15; 181(2):1548-55. PMID: 18606710.
    View in: PubMed
  19. Readinger JA, Schiralli GM, Jiang JK, Thomas CJ, August A, Henderson AJ, Schwartzberg PL. Selective targeting of ITK blocks multiple steps of HIV replication. Proc Natl Acad Sci U S A. 2008 May 6; 105(18):6684-9. PMID: 18443296.
    View in: PubMed
  20. Klatt A, Zhang Z, Kalantari P, Hankey PA, Gilmour DS, Henderson AJ. The receptor tyrosine kinase RON represses HIV-1 transcription by targeting RNA polymerase II processivity. J Immunol. 2008 Feb 1; 180(3):1670-7. PMID: 18209063.
    View in: PubMed
  21. Zhang Z, Klatt A, Henderson AJ, Gilmour DS. Transcription termination factor Pcf11 limits the processivity of Pol II on an HIV provirus to repress gene expression. Genes Dev. 2007 Jul 1; 21(13):1609-14. PMID: 17606639.
    View in: PubMed
  22. Zhang Z, Klatt A, Gilmour DS, Henderson AJ. Negative elongation factor NELF represses human immunodeficiency virus transcription by pausing the RNA polymerase II complex. J Biol Chem. 2007 Jun 8; 282(23):16981-8. PMID: 17442680.
    View in: PubMed
  23. Peng HH, Liang S, Henderson AJ, Dong C. Regulation of interleukin-8 expression in melanoma-stimulated neutrophil inflammatory response. Exp Cell Res. 2007 Feb 1; 313(3):551-9. PMID: 17141217.
    View in: PubMed
  24. Gekonge BN, Schiralli G, Schlegel RA, Henderson AJ. Signal transduction induced by apoptotic cells inhibits HIV transcription in monocytes/macrophages. J Leukoc Biol. 2006 Oct; 80(4):953-60. PMID: 16885500.
    View in: PubMed
  25. Wilson RL, Fuentes SM, Wang P, Taddeo EC, Klatt A, Henderson AJ, He B. Function of small hydrophobic proteins of paramyxovirus. J Virol. 2006 Feb; 80(4):1700-9. PMID: 16439527.
    View in: PubMed
  26. Ragin MJ, Hu J, Henderson AJ, August A. A role for the Tec family kinase ITK in regulating SEB-induced interleukin-2 production in vivo via c-jun phosphorylation. BMC Immunol. 2005; 6:19. PMID: 16042784.
    View in: PubMed
  27. Yang P, Henderson AJ. Nef enhances c-Cbl phosphorylation in HIV-infected CD4+ T lymphocytes. Virology. 2005 Jun 5; 336(2):219-28. PMID: 15892963.
    View in: PubMed
  28. Tsutsui S, Noorbakhsh F, Sullivan A, Henderson AJ, Warren K, Toney-Earley K, Waltz SE, Power C. RON-regulated innate immunity is protective in an animal model of multiple sclerosis. Ann Neurol. 2005 Jun; 57(6):883-95. PMID: 15929040.
    View in: PubMed
  29. Peng HH, Hodgson L, Henderson AJ, Dong C. Involvement of phospholipase C signaling in melanoma cell-induced endothelial junction disassembly. Front Biosci. 2005; 10:1597-606. PMID: 15769649.
    View in: PubMed
  30. Lee ES, Kalantari P, Tsutsui Section S, Klatt A, Holden J, Correll PH, Power Section C, Henderson AJ. RON receptor tyrosine kinase, a negative regulator of inflammation, inhibits HIV-1 transcription in monocytes/macrophages and is decreased in brain tissue from patients with AIDS. J Immunol. 2004 Dec 1; 173(11):6864-72. PMID: 15557181.
    View in: PubMed
  31. Callahan MK, Halleck MS, Krahling S, Henderson AJ, Williamson P, Schlegel RA. Phosphatidylserine expression and phagocytosis of apoptotic thymocytes during differentiation of monocytic cells. J Leukoc Biol. 2003 Nov; 74(5):846-56. PMID: 12960250.
    View in: PubMed
  32. Cook JA, Albacker L, August A, Henderson AJ. CD28-dependent HIV-1 transcription is associated with Vav, Rac, and NF-kappa B activation. J Biol Chem. 2003 Sep 12; 278(37):35812-8. PMID: 12842899.
    View in: PubMed
  33. Callahan MK, Popernack PM, Tsutsui S, Truong L, Schlegel RA, Henderson AJ. Phosphatidylserine on HIV envelope is a cofactor for infection of monocytic cells. J Immunol. 2003 May 1; 170(9):4840-5. PMID: 12707367.
    View in: PubMed
  34. Hodgson L, Henderson AJ, Dong C. Melanoma cell migration to type IV collagen requires activation of NF-kappaB. Oncogene. 2003 Jan 9; 22(1):98-108. PMID: 12527912.
    View in: PubMed
  35. Nonnemacher MR, Hogan TH, Quiterio S, Wigdahl B, Henderson A, Krebs FC. Identification of binding sites for members of the CCAAT/enhancer binding protein transcription factor family in the simian immunodeficiency virus long terminal repeat. Biomed Pharmacother. 2003 Jan; 57(1):34-40. PMID: 12642035.
    View in: PubMed
  36. Hogan TH, Nonnemacher MR, Krebs FC, Henderson A, Wigdahl B. HIV-1 Vpr binding to HIV-1 LTR C/EBP cis-acting elements and adjacent regions is sequence-specific. Biomed Pharmacother. 2003 Jan; 57(1):41-8. PMID: 12642036.
    View in: PubMed
  37. Lee ES, Sarma D, Zhou H, Henderson AJ. CCAAT/enhancer binding proteins are not required for HIV-1 entry but regulate proviral transcription by recruiting coactivators to the long-terminal repeat in monocytic cells. Virology. 2002 Jul 20; 299(1):20-31. PMID: 12167337.
    View in: PubMed
  38. Cook JA, August A, Henderson AJ. Recruitment of phosphatidylinositol 3-kinase to CD28 inhibits HIV transcription by a Tat-dependent mechanism. J Immunol. 2002 Jul 1; 169(1):254-60. PMID: 12077252.
    View in: PubMed
  39. Lee ES, Zhou H, Henderson AJ. Endothelial cells enhance human immunodeficiency virus type 1 replication in macrophages through a C/EBP-dependent mechanism. J Virol. 2001 Oct; 75(20):9703-12. PMID: 11559803.
    View in: PubMed
  40. Popernack PM, Truong LT, Kamphuis M, Henderson AJ. Ectopic expression of CCAAT/enhancer binding protein beta (C/EBPbeta) in long-term bone marrow cultures induces granulopoiesis and alters stromal cell function. J Hematother Stem Cell Res. 2001 Oct; 10(5):631-42. PMID: 11672509.
    View in: PubMed
  41. Ross HL, Nonnemacher MR, Hogan TH, Quiterio SJ, Henderson A, McAllister JJ, Krebs FC, Wigdahl B. Interaction between CCAAT/enhancer binding protein and cyclic AMP response element binding protein 1 regulates human immunodeficiency virus type 1 transcription in cells of the monocyte/macrophage lineage. J Virol. 2001 Feb; 75(4):1842-56. PMID: 11160683.
    View in: PubMed
  42. Montecino-Rodriguez E, Truong LT, Henderson AJ. Long-term bone marrow cultures provide access to early lymphoid progenitors. J Hematother Stem Cell Res. 2001 Feb; 10(1):107-14. PMID: 11276364.
    View in: PubMed
  43. Hodgson L, Qiu W, Dong C, Henderson AJ. Use of green fluorescent protein-conjugated beta-actin as a novel molecular marker for in vitro tumor cell chemotaxis assay. Biotechnol Prog. 2000 Nov-Dec; 16(6):1106-14. PMID: 11101341.
    View in: PubMed
  44. Henderson A, Calame K. Transcriptional regulation during B cell development. Annu Rev Immunol. 1998; 16:163-200. PMID: 9597128.
    View in: PubMed
  45. Henderson AJ, Calame KL. CCAAT/enhancer binding protein (C/EBP) sites are required for HIV-1 replication in primary macrophages but not CD4(+) T cells. Proc Natl Acad Sci U S A. 1997 Aug 5; 94(16):8714-9. PMID: 9238043.
    View in: PubMed
  46. Merrell K, Wells S, Henderson A, Gorman J, Alt F, Stall A, Calame K. The absence of the transcription activator TFE3 impairs activation of B cells in vivo. Mol Cell Biol. 1997 Jun; 17(6):3335-44. PMID: 9154832.
    View in: PubMed
  47. Henderson AJ, Connor RI, Calame KL. C/EBP activators are required for HIV-1 replication and proviral induction in monocytic cell lines. Immunity. 1996 Jul; 5(1):91-101. PMID: 8758898.
    View in: PubMed
  48. Cooper C, Henderson A, Artandi S, Avitahl N, Calame K. Ig/EBP (C/EBP gamma) is a transdominant negative inhibitor of C/EBP family transcriptional activators. Nucleic Acids Res. 1995 Nov 11; 23(21):4371-7. PMID: 7501458.
    View in: PubMed
  49. Henderson AJ, Zou X, Calame KL. C/EBP proteins activate transcription from the human immunodeficiency virus type 1 long terminal repeat in macrophages/monocytes. J Virol. 1995 Sep; 69(9):5337-44. PMID: 7636977.
    View in: PubMed
  50. Henderson AJ, Calame KL. Lessons in transcriptional regulation learned from studies on immunoglobulin genes. Crit Rev Eukaryot Gene Expr. 1995; 5(3-4):255-80. PMID: 8834227.
    View in: PubMed
  51. Henderson AJ, McDougall S, Leiden J, Calame KL. GATA elements are necessary for the activity and tissue specificity of the T-cell receptor beta-chain transcriptional enhancer. Mol Cell Biol. 1994 Jun; 14(6):4286-94. PMID: 8196665.
    View in: PubMed
  52. Henderson AJ, Narayanan R, Collins L, Dorshkind K. Status of kappa L chain gene rearrangements and c-kit and IL-7 receptor expression in stromal cell-dependent pre-B cells. J Immunol. 1992 Sep 15; 149(6):1973-9. PMID: 1381391.
    View in: PubMed
  53. Henderson AJ, Johnson A, Dorshkind K. Functional characterization of two stromal cell lines that support B lymphopoiesis. J Immunol. 1990 Jul 15; 145(2):423-8. PMID: 1694879.
    View in: PubMed
  54. Henderson AJ, Dorshkind K. In vitro models of B lymphocyte development. Semin Immunol. 1990 May; 2(3):181-7. PMID: 2129906.
    View in: PubMed
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