Photo of Dr. Lifson

Jeffrey D. Lifson, M.D.

Retroviral Pathogenesis Section

SAIC-Frederick, Inc
Frederick National Laboratory for Cancer Research
Building 535, Suite 510
Frederick, MD 21702-1201

Tel: 301-846-1408
Fax: 301-846-5588
Email: lifsonj@mail.nih.gov

Biography

Dr. Lifson received his M.D. from Northwestern University Medical School in 1982, then pursued residency and research fellowship training in the Department of Pathology at the Stanford University School of Medicine. He became involved in AIDS-related research in 1983, playing a key role in establishing the first program in the United States to try to prevent transfusion-mediated transmission of AIDS through laboratory testing, while also conducting basic in vitro studies of AIDS pathogenesis. After several years of continuing research in AIDS pathogenesis while working in the biotechnology industry, Dr. Lifson moved to the Frederick National Laboratory for Cancer Research in 1995, establishing the Retroviral Pathogenesis Section within the AIDS Vaccine Program. His work there has focused on the continuing development and application of quantitative virological and immunological methods for understanding retroviral pathogenesis and evaluating approaches for the prevention and treatment of retroviral infection and AIDS. In 2002, Dr. Lifson was named the director of the AIDS Vaccine Program, which became the AIDS and Cancer Virus Program in 2008.

Research Description

The Retroviral Pathogenesis Section conducts both in vitro and in vivo studies aimed at improving our understanding of the basis of lentiviral pathogenesis, particularly those aspects relevant to the development and evaluation of effective means of preventing and treating HIV infection and AIDS. The work spans a broad scope from in vitro studies of the structure of viral molecules involved in infection, to the interaction of viral particles with immune system cells, to in vitro studies, to in vivo studies in non-human primate models. The work emphasizes both applied studies such as the in vitro and in vivo evaluation of candidate vaccine and treatment approaches (immunogens, adjuvants, modes of immunization) and more basic studies aimed at characterizing fundamental processes of virus/host interactions potentially relevant to prevention and treatment. Areas of particular interest include development of improved non-human primate models involving minimally chimeric HIV strains, non-human primate models for evaluating virus suppressive antiretroviral drug treatment and approaches for targeting residual virus and latently infected reservoirs in treated individuals, the dynamics of virus/host interactions during primary infection, the mechanistic basis and consequences of chronic generalized immune activation in pathogenic primate lentiviral infection, and characterization of the virus/host interactions associated with situations of effective host control of replication, including vaccine induced protection.

Key Collaborators

  • Marcus Altfeld, Harvard Medical School/Ragon Institute
  • Cristian Apetrei, University of Pittsburgh
  • Nina Bhardwaj, New York University
  • Paul Bieniasz, HHMI/Rockefeller University/ADARC
  • Norbert Bischofberger, Gilead Sciences
  • Jason Brenchley, NIAID/NIH
  • Mary Carrington, NCI Frederick
  • Ron Desrosiers, Harvard Medical School/NENPRC
  • Danny Douek, VRC/NIAID/NIH
  • Romas Geleziunas, Gilead Sciences
  • Ashley Haase, University of Minnesota
  • Beatrice Hahn, University of Pennsylvania
  • Theodora Hatziioannou, ADARC
  • Daria Hazuda, Merck Research Laboratories
  • Vanessa Hirsch, NIAID/NIH
  • Jim Hoxie, University of Pennsylvania
  • R. Paul Johnson, Harvard Medical School/ NENPRC
  • Vineet KewalRamani, HIV-DRP/NCI
  • Mal Martin, NIAID/NIH
  • Chris Miller, University of California, Davis/CNPRC
  • Louis Picker, OHSU/VGTI/ONPRC
  • Melissa Robbiani, The Population Council
  • Tim Schacker, University of Minnesota
  • Joern Schmitz, Harvard Medical School/ BIDMC
  • Bob Seder, VRC/NIAID/NIH
  • George Shaw, University of Pennsylvania
  • Guido Silvestri, Emory University
  • Sriram Subramaniam, NCI
  • Ron Veazey, Tulane University/TNPRC

Recent Publications

  1. Rodriguez-Garcia M, Porichis F, deJong OG, Diefenbach TJ, Lifson JD, Freeman GJ, Walker BD, Kaufmann DE, Kavanagh DG: Expression of PD-L1 and PD-L2 on human macrophages is up-regulated by HIV-1 and differentially modulated by IL-10. J Leukoc Biol 89(4):507-515, 2011. Epub 2010 Nov 19. PMID: 21097698
  2. Zeng M, Smith AJ, Wietgrefe SW, Southern PJ, Schacker TW, Reilly CS, Estes JD, Burton GF, Silvestri G, Lifson JD, Carlis JV, Haase AT. Cumulative mechanisms of lymphoid tissue fibrosis and T cell depletion in HIV-1 and SIV infections. J Clin Invest 121(3):998-1008, 2011. 2011 Mar 1. PMID: 21393864
  3. Chang J, Lindsay RJ, Kulkarni S, Lifson JD, Carrington M, Altfeld M: Polymorphisms in interferon regulatory factor 7 reduce interferon-α responses of plasmacytoid dendritic cells to HIV-1. AIDS 25(5):715-17, 2011. 2011 Mar 13. PMID: 21297422
  4. Shankar EM, Che KF, Messmer D, Lifson JD, Larsson M: Expression of a broad array of negative costimulatory molecules and blimp-1 in T-cells following priming by HIV-1 pulsed dendritic cells. Mol Med 17(3-4):229-240, 2011. doi: 10.2119/molmed.2010.00175. Epub 2010 Nov 17. PMID: 21103670
  5. Kenney J, Aravantinou M, Singer R, Hsu M, Rodriguez A, Kizima L, Abraham CJ, Menon R, Seidor S, Chudolij A, Gettie A, Blanchard J, Lifson JD, Piatak M Jr, Fernandez-Romero JA, Zydowsky TM, Robbiani M: An antiretroviral/zinc combination gel provides 24 hours of complete protection against vaginal SHIV infection in macaques. PLoS One 6(1):e15835, 2011. PMID: 21246052
  6. Garcia F, Climent N, Assoumou L, Gil C, González N, Alcamí J, León A, Romeu J, Dalmau J, Martínez-Picado J, Lifson J, Autran B, Costagliola D, Clotet B, Gatell JM, Plana M, Gallart T; for the DCV2/MANON07- AIDS Vaccine Research Objective Study Group: A therapeutic dendritic cell-based vaccine for HIV-1 infection. J Infect Dis 203(4):473-478, 2011. Epub 2011 Jan 13. PMID: 21233310
  7. Kearney M, Spindler J, Shao W, Maldarelli F, Palmer S, Hu SL, Lifson JD, Kewalramani VN, Mellors JW, Coffin JM, Ambrose Z: Genetic diversity of Simian Immunodeficiency Virus encoding HIV-1 reverse transcriptase (RT-SHIVmne) persists in macaques despite antiretroviral therapy. J Virol 85(2):1067-1076, 2011. Epub 2010 Nov 17. PMID: 21084490
  8. Sabado RL, O'Brien M, Subedi A, Qin L, Hu N, Taylor E, Dibben O, Stacey A, Fellay J, Shianna KV, Siegal F, Shodell M, Shah K, Larsson M, Lifson J, Nadas A, Marmor M, Hutt R, Margolis D, Garmon D, Markowitz M, Valentine F, Borrow P, Bhardwaj N: Evidence of dysregulation of dendritic cells in primary HIV infection. Blood 116(19):3839-3852, 2010. Epub 2010 Aug 6. PMID: 20693428.
  9. Vagenas P, Aravantinou M, Williams VG, Jasny E, Piatak M, Lifson JD, Salazar AM, BlanchardJL, Gettie A, Robbiani M: A tonsillar polyICLC/AT-2 SIV therapeutic vaccine maintains low viremia following antiretroviral therapy cessation. PLoS One 5(9):e12891, 2010. Epub 2010 Sep 21. PMID: 20877632.
  10. Estes JD, Harris LD, Klatt NR, Tabb B, Pittaluga S, Paiardini M, Barclay GR, Smedley J, Pung R, Oliveira KM, Hirsch VM, Silvestri G, Douek DC, Miller CJ, Haase AT, Lifson J, Brenchley JM: Damaged intestinal epithelial integrity linked to microbial translocation in pathogenic simian immunodeficiency virus infections. PLoS Pathog 6(8):e1001052, 2010. Epub 2010 Aug 19. PMID: 20808901.
  11. Leone A, Rohankhedkar M, Okoye A, Legasse A, Axthelm MK, Villinger F, Piatak M Jr, Lifson JD, Assouline B, Morre M, Picker LJ, Sodora DL: Increased CD4+ T cell levels during IL-7 administration of antiretroviral therapy-treated simian immunodeficiency virus-positive macaques are not dependent on strong proliferative responses. J Immunol 185(3):1650-1659, 2010. Epub 2010 Jul 9. PMID: 20622118
  12. Harris LD, Klatt NR, Vinton C, Briant JA, Tabb B, Ladell K, Lifson J, Estes JD, Price DA, Hirsch VM, Brenchley JM: Mechanisms underlying {gamma}-{delta} T cell subset perturbations in SIV-infected Asian rhesus macaques. Blood 116(20):4148-4157, 2010. Epub 2010 Jul 26. PMID: 20660793
  13. White TA, Bartesaghi A, Borgnia MJ, Meyerson JR, de la Cruz MJ, Bess JW, Nandwani R, Hoxie JA, Lifson JD, Milne JL, Subramaniam S: Molecular architectures of trimeric SIV and HIV-1 envelope glycoproteins on intact viruses: strain-dependent variation in quaternary structure. PLoS Pathog 6(12):e1001249, 2010. PMID: 21203482
  14. Salisch NC, Kaufmann DE, Awad AS, Reeves RK, Tighe DP, Li Y, Piatak M Jr, Lifson JD, Evans DT, Pereyra F, Freeman GJ, Johnson RP: Inhibitory TCR coreceptor PD-1 is a sensitive indicator of low-level replication of SIV and HIV-1. J Immunol 184(1):476-87, 2010. Epub 2009 Nov 30. PMID: 19949078.
  15. Kim WK, Sun Y, Do H, Autissier P, Halpern EF, Piatak M Jr, Lifson JD, Burdo TH, McGrath MS, Williams K: Monocyte heterogeneity underlying phenotypic changes in monocytes according to SIV disease stage. J Leukoc Biol 87(4):557-567, 2010. Epub 2009 Oct 20. PMID: 19843579.
  16. Klatt NR, Harris LD, Vinton CL, Sung H, Briant JA, Tabb B, Morcock D, McGinty JW, Lifson JD, Lafont BA, Martin MA, Levine AD, Estes JD, Brenchley JM: Compromised gastrointestinal integrity in pigtail macaques is associated with increased microbial translocation, immune activation and IL-17 production in the absence of SIV infection. Mucosal Immunology 3(4):387-398, 2010. Epub 2010 Mar 31. PMID: 20357762.
  17. Harris LD, Tabb B, Sodora DL, Paiardini M, Klatt NR, Douek DC, Silvestri G, Muller-Trutwin M, Vasile-Pandrea I, Apetrei C, Hirsch V, Lifson JD, Brenchley JM, Estes JD: Downregulation of robust acute type I IFN responses distinguishes nonpathogenic SIV infection of natural hosts from pathogenic SIV infection of rhesus macaques. J Virol 84(15):7886-7891, 2010. Epub 2010 May 19. PMID: 20484518.
  18. Che KF, Sabado RL, Shankar EM, Tjomsland V, Messmer D, Bhardwaj N, Lifson JD, Larsson M: HIV-1 impairs in vitro priming of naïve T-cells and gives rise to contact-dependent suppressor T-cells. Eur J Immunol 40(8):2248-2258, 2010. PMID: 20455275
  19. Felts RL, Narayan K, Estes JD, Shi D, Trubey CM, Fu J, Hartnell LM, Ruthel GT, Schneider DK, Nagashima K, Bess JW Jr, Bavari S, Lowekamp BC, Bliss D, Lifson JD, Subramaniam S: 3D visualization of HIV transfer at the virological synapse between dendritic cells and T-cells. PNAS 107(3):13336-13341, 2010. Epub 2010 Jul 12. PMID: 206224966
  20. Alpert MD, Rahmberg AR, Neidermyer W, Ng SK, Carville A, Camp JV, Wilson RL, Piatak M Jr, Mansfield KG, Li W, Miller CJ, Lifson JD, Kozlowski PA, Evans DT. Envelope-modified single-cycle simian immunodeficiency virus selectively enhances antibody responses and partially protects against repeated, low-dose vaginal challenge. J Virol 84(20):10748-64, 2010. Epub 2010 Aug 11. PMID: 20702641
  21. Pugach P, Krarup A, Gettie A, Kuroda M, Blanchard J, Piatak M Jr, Lifson JD, Trkola A, Robbiani M: In vivo binding and retention of CD4-specific DARPin 57.2 in macaques. PLoS One 5(8):e12455, 2010. Epub 2010 Aug 27. PMID: 20805996.
  22. Bolton DL, Minang JT, Trivett MT, Song K, Tuscher JJ, Li Y, Piatak M Jr, O’Connor D, Lifson JD, Roederer M, Ohlen C: Trafficking, persistence, and activation state of adoptively transferred allogeneic and autologous SIV-specific CD8+ T cell clones during acute and chronic infection of rhesus macaques. J Immunol 184(1):303-314, 2010. Epub 2009 Nov 30. PMID: 19949089.
  23. Minang JT, Trivett MT, Bolton DL, Trubey CM, Estes JD, Li Y, Smedley J, Pung R, Rosati M, Jalah R, Pavlakis GN, Felber BK, Piatak M Jr, Roederer M, Lifson JD, Ott D, Ohlen C: Distribution, persistence and efficacy of adoptively transferred central and effector memory-derived autologous SIV-specific CD8+ T cell clones in rhesus macaques during acute infection. J Immunol 184(1):315-326, 2010. Epub 2009 Nov 30. PMID: 19949091.
  24. Kader M, Wang X, Piatak M, Lifson J, Roederer M, Veazey R, Mattapallil JJ: Alpha4(+)beta7(hi)CD4(+) memory T cells harbor most Th-17 cells and are preferentially infected during acute SIV infection. Mucosal Immunol 2:439-449, 2009.
  25. Boukari H, Brichacek B, Stratton P, Mahoney SF, Lifson JD, Margolis L, Nossal R: Movements of HIV-virions in human cervical mucus. Biomarcomolecules 10(9):2482-2488, 2009. PMID: 19711976.
  26. Shao W, Kearney MF, Maldarelli F, Mellors JW, Stephens RM, Lifson JD, KewalRamani VN, Ambrose Z, Coffin JM, Palmer SE: RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. Retrovirology 6:101, 2009. PMID: 19889213.
  27. Crostarosa F, Aravantinou M, Akpogheneta OJ, Jasny E, Shaw A, Kenney J, Piatak M Jr, Lifson JD, Teitelbaum A, Hu L, Chudolij A, Zydowsky TM, Blanchard J, Gettie A, Robbiani M: A macaque model to study vaginal HSV-2/immunodeficiency virus co-infection and the impact of HSV-2 on microbicide efficacy. PLoS ONE 4(11):e8060, 2009. PMID: 20011586.
  28. Vagenas P, Williams VG, Piatak M Jr, Bess JW Jr, Lifson JD, Blanchard JL, Gettie A, Robbiani M: Tonsillar application of AT-2 SIV affords partial protection against rectal challenge with SIVmac239. JAIDS 52(4):433-442, 2009. PMID: 19779309.
  29. Huang J, Goedert JJ, Sundberg E, Cung TDH, Burke P, Martin MP, Lifson J, Lichterfeld M, Carrington M, Yu XG: HLA-B*35-Px-mediated acceleration of HIV-1 infection by increased inhibitory immunoregulatory impulses. J Exp Med 206(13):2959-2966, 2009. Epub 2009 Dec 14. PMID: 20008523.
  30. Kader M, Bixler S, Piatak M, Lifson J, Mattapallil JJ: Anti-retroviral therapy fails to restore the severe Th-17: Tc-17 imbalance observed in peripheral blood during SIV infection. J Med Primatol 38 Suppl 1:32-38, 2009. PMID: 19863676.

Staffing

  • Gregory Q. Del Prete, Ph.D., Scientist I
  • Robert Gorelick, Ph.D., Staff Scientist
  • Douglas K. Schneider, Research Associate II