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Stephen Arnoff

Earl Henderson, PhD

 

Professor, Microbiology and Immunology

Professor, Fels Institute for Cancer Research and Molecular Biology

Telephone:  215-707- 3583

Fax:  215-707-7788

Email: eehender@temple.edu

 

Department of Microbiology and Immunology

Fels Institute for Cancer Research and Molecular Biology

Center for Substance Abuse Research

 

Educational Background:

 

University of Chicago, PhD

 

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Research Interests:

 

Dr. Henderson's major research interests are revolving around several projects. The first involves the etiology and evolution of EBV-associated T cell lymphomas in patients with AIDS. AIDS-related Epstein-Barr virus (EBV)-associated T cell lymphomas are emerging as a new, distinct histopathological entity. The pathway whereby EBV infects T cells as well as the initial EBV transcriptional program in T cells has not been established. Dr. Henderson's laboratory is actively working to characterize these pathways. Demonstration of EBV mRNA transcripts encoding immediate-early transcriptional transactivators in EBV-infected T cells provides the first evidence for a possible mechanism whereby EBV could contribute to T cell proliferation and EBV-associated T cell malignancies. Identification of EBV transcripts in T cell lymphomas will lead to improved therapy and prevention of these lymphomas.

 

The second research project is related to Herpesvirus saimiri. Human T lymphocytes are transformed by this virus in vitro to continuous proliferation. It has been previously shown that H. saimiri-transformed human T cell lines are a permissive system for HIV-1 and -2 replication and are highly susceptible to infection by HIV-1 and 2. Two proteins of H. saimiri, StpC and Tip, are required for T cell transformation and are unique to this herpesvirus. The successful transduction of human T cells with retroviral vectors expressing H. saimiri proteins StpC and Tip has allowed us to extend the before-mentioned observations and investigate the role of StpC and Tip in replication of HIV 1 T-tropic strains (IIIB, MN and RF) in human T cell lines. StpC expression in Molt4 dramatically enhanced HIV-1 replication. In contrast, Tip expression in Molt4 cells inhibited HIV-1 replication and cytopathic effects relative to Molt4 cells transduced with the empty vector alone. A better understanding of the effects of Tip and StpC proteins on the biology of human hemopoietic stem cells may lead to novel therapeutic interventions for the treatment of AIDS.

 

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PUBMED PUBLICATIONS :


Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)

18006034. Smirnova EV, Collingwood TS, Bisbal C, Tsygankova OM, Bogush M, Meinkoth JL, Henderson EE, Annan RS, Tsygankov AY, TULA proteins bind to ABCE-1, a host factor of HIV-1 assembly, and inhibit HIV-1 biogenesis in a UBA-dependent fashion. Virology 372:1(10-23)2008 Mar 1

17266559. Raymond AD, Hasham M, Tsygankov AY, Henderson EE, Herpesvirus saimiri terminal membrane proteins modulate HIV-1 replication by altering Nef and Tat functions. Curr HIV Res 5:1(79-86)2007 Jan

17263642. Dimitrova DI, Reichenbach NL, Yang X, Pfleiderer W, Charubala R, Gaughan JP, Suh B, Henderson EE, Suhadolnik RJ, Rogers TJ, Inhibition of HIV type 1 replication in CD4+ and CD14+ cells purified from HIV type 1-infected individuals by the 2-5A agonist immunomodulator, 2-5A(N6B). AIDS Res Hum Retroviruses 23:1(123-34)2007 Jan

16891001. Turner LS, Tsygankov AY, Henderson EE, StpC-based gene therapy targeting latent reservoirs of HIV-1. Antiviral Res 72:3(233-41)2006 Dec

16780912. Raymond AD, Hasham M, Tsygankov AY, Henderson EE, H. saimiri tyrosine-kinase interacting protein inhibits Tat function: a prototypic strategy for restricting HIV-1-induced cytopathic effects in immune cells. Virology 352:2(253-67)2006 Sep 1

15957958. Dimitrova DI, Yang X, Reichenbach NL, Karakasidis S, Sutton RE, Henderson EE, Rogers TJ, Suhadolnik RJ, Lentivirus-mediated transduction of PKR into CD34(+) hematopoietic stem cells inhibits HIV-1 replication in differentiated T cell progeny. J Interferon Cytokine Res 25:6(345-60)2005 Jun

15183053. Raymond AD, Hasham MG, Tsygankov AY, Henderson EE, Herpesvirus saimiri-encoded proteins Tip and StpC modulate human immunodeficiency virus type 1 replication in T-cell lines and lymphocytes independently of viral tropism. Virology 324:1(60-6)2004 Jun 20

12972507. Szabo I, Wetzel MA, Zhang N, Steele AD, Kaminsky DE, Chen C, Liu-Chen LY, Bednar F, Henderson EE, Howard OM, Oppenheim JJ, Rogers TJ, Selective inactivation of CCR5 and decreased infectivity of R5 HIV-1 strains mediated by opioid-induced heterologous desensitization. J Leukoc Biol 74:6(1074-82)2003 Dec

12726730. Steele AD, Henderson EE, Rogers TJ, Mu-opioid modulation of HIV-1 coreceptor expression and HIV-1 replication. Virology 309:1(99-107)2003 Apr 25

12048358. Homan JW, Steele AD, Martinand-Mari C, Rogers TJ, Henderson EE, Charubala R, Pfleiderer W, Reichenbach NL, Suhadolnik RJ, Inhibition of morphine-potentiated HIV-1 replication in peripheral blood mononuclear cells with the nuclease-resistant 2-5A agonist analog, 2-5A(N6B). J Acquir Immune Defic Syndr 30:1(9-20)2002 May 1

11878903. Wetzel MA, Steele AD, Henderson EE, Rogers TJ, The effect of X4 and R5 HIV-1 on C, C-C, and C-X-C chemokines during the early stages of infection in human PBMCs. Virology 292:1(6-15)2002 Jan 5

11727782. Szabo I, Wetzel M, McCarthy L, Steele A, Henderson EE, Howard MZ, Oppenheim JJ, Rogers TJ, Interactions of opioid receptors, chemokines, and chemokine receptors. Adv Exp Med Biol 493:(69-74)2001

11086093. Wetzel MA, Steele AD, Eisenstein TK, Adler MW, Henderson EE, Rogers TJ, Mu-opioid induction of monocyte chemoattractant protein-1, RANTES, and IFN-gamma-inducible protein-10 expression in human peripheral blood mononuclear cells. J Immunol 165:11(6519-24)2000 Dec 1

10652585. Guan M, Romano G, Henderson EE, Epstein-Barr virus (EBV)-induced long-term proliferation of CD4+ lymphocytes leading to T lymphoblastoid cell lines carrying EBV. Anticancer Res 19:4B(3007-17)1999 Jul-Aug

10544137. Henderson EE, Tsygankov AY, Merlo JJ, Romano G, Guan M, Altered replication of human immunodeficiency virus type 1 (HIV-1) in T cell lines retrovirally transduced to express Herpesvirus saimiri proteins StpC and/or Tip. Virology 264:1(125-33)1999 Nov 10

9872325. Garriga J, Peng J, Parreño M, Price DH, Henderson EE, Graña X, Upregulation of cyclin T1/CDK9 complexes during T cell activation. Oncogene 17:24(3093-102)1998 Dec 17

9858880. Guan M, Romano G, Henderson EE, In situ RT-PCR detection of Epstein-Barr virus immediate-early transcripts in CD4+ and CD8+ T lymphocytes. Anticancer Res 18:5A(3171-80)1998 Sep-Oct

9712368. Salgame P, Guan MX, Agahtehrani A, Henderson EE, Infection of T cell subsets by HIV-1 and the effects of interleukin-12. J Interferon Cytokine Res 18:7(521-8)1998 Jul

9703884. Merlo JJ, Romano G, Gordon SS, Feshchenko EA, Peng G, Henderson EE, Tsygankov AY, Human T cells transduced by a retroviral vector to express Herpesvirus saimiri proteins TIP and STPC. Anticancer Res 18:4A(2389-96)1998 Jul-Aug

9344904. Romano G, Guan M, Long WK, Henderson EE, Differential effects on HIV-1 gene regulation by EBV in T lymphocytic and promonocytic cells transduced to express recombinant human CR2. Virology 237:1(23-32)1997 Oct 13

9171219. Guan M, Tudor G, Yang JY, Henderson EE, Structure and origin of HIV type 1 DNA in persistently infected B lymphoblastoid cell lines. AIDS Res Hum Retroviruses 13:9(751-7)1997 Jun 10

9007201. Zhang RD, Guan M, Park Y, Tawadros R, Yang JY, Gold B, Wu B, Henderson EE, Synergy between human immunodeficiency virus type 1 and Epstein-Barr virus in T lymphoblastoid cell lines. AIDS Res Hum Retroviruses 13:2(161-71)1997 Jan 20

8794395. Guan M, Zhang RD, Wu B, Henderson EE, Infection of primary CD4+ and CD8+ T lymphocytes by Epstein-Barr virus enhances human immunodeficiency virus expression. J Virol 70:10(7341-6)1996 Oct

7890727. Sobol RW, Henderson EE, Kon N, Shao J, Hitzges P, Mordechai E, Reichenbach NL, Charubala R, Schirmeister H, Pfleiderer W, Inhibition of HIV-1 replication and activation of RNase L by phosphorothioate/phosphodiester 2',5'-oligoadenylate derivatives. J Biol Chem 270:11(5963-78)1995 Mar 17

7856104. Mordechai E, Kon N, Henderson EE, Suhadolnik RJ, Activation of the interferon-inducible enzymes, 2',5'-oligoadenylate synthetase and PKR by human T-cell leukemia virus type I Rex-response element. Virology 206:2(913-22)1995 Feb 1

8024587. Yang JY, Schwartz A, Henderson EE, Inhibition of 3'azido-3'deoxythymidine-resistant HIV-1 infection by dehydroepiandrosterone in vitro. Biochem Biophys Res Commun 201:3(1424-32)1994 Jun 30

7507284. Zhang RD, Henderson EE, CD4 mRNA expression in CD19-positive B cells and its suppression by the Epstein-Barr virus. Virology 198:2(709-13)1994 Feb

7692906. Yang JY, Schwartz A, Henderson EE, Inhibition of HIV-1 latency reactivation by dehydroepiandrosterone (DHEA) and an analog of DHEA. AIDS Res Hum Retroviruses 9:8(747-54)1993 Aug

8441681. Green AP, deRiel JK, Henderson EE, Structure/function analysis of the Ala116-->Lys121 region of endonuclease V by random targeted mutagenesis. Nucleic Acids Res 21:3(727-32)1993 Feb 11

8237587. Adler MW, Geller EB, Rogers TJ, Henderson EE, Eisenstein TK, Opioids, receptors, and immunity. Adv Exp Med Biol 335:(13-20)1993

1379369. Henderson EE, Tudor G, Yang JY, Inactivation of the human immunodeficiency virus type 1 (HIV-1) by ultraviolet and X irradiation. Radiat Res 131:2(169-76)1992 Aug

1708929. Henderson EE, Yang JY, Zhang RD, Bealer M, Altered HIV expression and EBV-induced transformation in coinfected PBLs and PBL subpopulations. Virology 182:1(186-98)1991 May

2155388. Seal G, Henderson EE, Sirover MA, Immunological alteration of the Bloom's syndrome uracil DNA glycosylase in Epstein-Barr virus-transformed human lymphoblastoid cells. Mutat Res 243:3(241-8)1990 Mar

2927423. Henderson EE, Valerie K, Green AP, de Riel JK, Host cell reactivation of CAT-expression vectors as a method to assay for cloned DNA-repair genes. Mutat Res 220:2-3(151-60)1989 Mar-May

2538121. Fronko GE, Long WK, Wu B, Papadopoulos T, Henderson EE, Relationship between methylation status and expression of an Epstein-Barr virus (EBV) capsid antigen gene. Biochem Biophys Res Commun 159:1(263-70)1989 Feb 28

2536010. Henderson EE, Franks C, Fronko G, Chemical carcinogen Epstein-Barr virus (EBV) synergism: EBV genome amplification and site-specific mutation during transformation. Int J Cancer 43:1(72-9)1989 Jan 15

2835490. Henderson EE, Physicochemical-viral synergism during Epstein-Barr virus infection: a review. J Natl Cancer Inst 80:7(476-83)1988 Jun 1

2837212. Fronko GE, Suhadolnik RJ, Vonderheid EC, Karikó K, Reichenbach NL, Chavin KD, Henderson EE, Decreased Epstein-Barr virus-induced transformation, and elevated 2-5A synthetase and RNase L activity in peripheral blood mononuclear cells from patients treated with recombinant interferon alfa 2b. Biochem Biophys Res Commun 153:1(448-53)1988 May 31

2446955. Valerie K, Fronko G, Long W, Henderson EE, Nilsson B, Uhlén M, de Riel JK, Production and detection of coliphage T4 endonuclease V polyclonal and monoclonal antibodies using staphylococcal protein-A hybrid proteins. Gene 58:1(99-107)1987

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graduate students :

 

Sean Roberts

Lorianne Turner

Filip Bednar (Co-advisor, Thomas J. Rogers, PhD)

David Kaminsky (Co-advisor, Thomas J. Rogers, PhD)

Certain Recent Graduates:


Adebimpe Afolabi, MD, MS

Émigré Physicians Program

New York College of Osteopathic Medicine of New York Institute of Technology


Michele Wetzel Kutzler, PhD

Postdoctoral Fellow, Department of Pathology and Laboratory Medicine

University of Pennsylvania


Andrea Raymond, PhD

Postdoctoral Fellow, Department of Medicine

University of Pennsylvania

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grant support :

 

Current or Recent Grant Support of Active Projects:

 

Earl Henderson, PhD as Co-Investigator:

National Institutes of Health, T32 A107101, C. D. Platsoucas, PhD, Principal Investigator/Program Director; Microbiology and Immunology Training Program

 

National Institutes of Health, P30 DA13429, M. W. Adler, PhD, Principal Investigator; Center on Intersystem Regulation by Drugs of Abuse

 

National Institutes of Health, 1 DA14230, T. J. Rogers, PhD, Principal Investigator; Interactions between Opioid and Chemokine Receptors Relative to HIV

 

National Institutes of Health, R01 DA06650, M. W. Adler, PhD, Principal Investigator; Opioids, Cannabinoids, Chemokines: Neuroimmune Interactions

 

National Institutes of Health, DA016544, T. J. Rogers, PhD, Principal Investigator; HIV Infection and Opioid-induced Immunoregulation

 

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