Photo of Dr. Estes

Jacob D. Estes, Ph.D.

PI/Principal Scientist, Retroviral Immunopathology Section
Head, Tissue Core Analysis Core

Leidos Biomedical Research, Inc.
Frederick National Laboratory for Cancer Research
Frederick, MD 21702-1201

Tel: 301-846-7641
Fax: 301-846-5588
Email: estesj@mail.nih.gov

Biography

Jacob D. Estes, Ph.D., is a Principal Scientist/Principal Investigator in the AIDS and Cancer Virus Program (ACVP) at the Frederick National Laboratory for Cancer Research operated by Leidos Biomedical Research, Inc., and currently heads both the Retroviral Immunopathology Section and Tissue Analysis Core within the ACVP. Dr. Estes obtained his Ph.D. at Brigham Young in the laboratory of Dr. Gregory Burton studying the contributions of follicular dendritic cells and the germinal center microenvironment to HIV pathogenesis. Dr. Estes continued his work as a postdoctoral fellow in the laboratory of Dr. Ashley Haase in the Department of Microbiology at the University of Minnesota, focusing on the in vivo immunopathogology of lentiviral infections in lymphoid tissues in both human patient cohorts and non-human primate models. Dr. Estes joined the AIDS and Cancer Virus Program in 2007.

Research Description for Retroviral Immunopathology Section

The Retroviral Immunopathology Section (RIPS) studies various aspects of lentiviral mucosal transmission and pathogenesis using state-of-the art tissue analysis capabilities (i.e. immunofluorescence, immunohistochemistry, in situ hybridization, quantitative image analysis, laser capture microdissection, etc.) to better understand in vivo the host-viral interactions following mucosal infection and the immunopathologenic mechanisms and processes of disease progression. Dr. Estes' major research aims are focused on: i) understanding and further elucidating the biology, mechanisms and barriers to lentiviral mucosal transmission and viral dissemination in order to better guide preventative strategies; ii) understanding and identifying the establishment, tissue sanctuaries and cellular sources of persistent lentiviral reservoirs utilizing novel NHP and viral systems; and iii) understanding the factors driving systemic immune activation and disease progression to guide adjunctive therapeutic intervention strategies that can be used to ameliorate immune activation and its associated pathologic consequences.

Tissue Analysis Core Description

The Tissue Analysis Core (TAC) provides state-of-the art tissue analysis capabilities (i.e. immunofluorescence, immunohistochemistry, in situ hybridization, quantitative image analysis, laser capture microdissection) for ACVP directed studies and in support of intramural and extramural investigators working on collaborative studies relevant to key questions in HIV/AIDS research, with an emphasis on analysis of specimens from non-human primate (NHP) models. The Tissue Analysis Core is working with ACVP investigators and a network of collaborators to better understand HIV/SIV mucosal transmission, reservoir biology, pathogenesis and therapeutic intervention strategies. To accomplish the diverse array of collaborative studies, the Tissue Analysis Core has invested extensive time and resources to develop and optimize novel next-generation, highly sensitive in situ hybridization strategies for detection of lentiviruses in fixed tissue samples. In addition, Tissue Analysis Core has partnered with the Pathology and Histotechnology Laboratory (PHL) at the FNLCR to generate, produce and make available innovative lineage specific viral RNA riboprobe reagents for in situ hybridization detection of an array viruses in tissue samples (i.e. HIV-1 clades A, B, C, D and CRF01_AE, SIVmac239 lineage 8, SIVsmE660 lineage1, SIVsmM946 lineage 2, SIVsmFTq lineage 5, SIVsmD215 lineage 6, SIVsmSL92B and SIVagm).

Recent Publications

  1. Del Prete GQ, Ailers B, Moldt B, Keele BF, Estes JD, Rodriguez A, Sampias M, Oswald K, Fast R, Trubey CM, Chertova E, Smedley J, LaBranche CC, Montefiori DC, Burton DR, Shaw GM, Markowitz M, Piatak M Jr, KewalRamani VN, Bieniasz PD, Lifson JD, Hatziioannou T: Selection of unadapted, pathogenic SHIVs encoding newly transmitted HIV-1 envelope proteins. Cell Host Microbe 16(3):412-418, 2014. doi: 10.1016/j.chom.2014.08.003.PMID: 25211081
  2. Del Prete GQ, Shoemaker R, Oswald K, Lara A, Trubey CM, Fast R, Schneider DK, Kiser R, Coalter V, Wiles A, Wiles R, Freemire B, Keele BF, Estes JD, Quiñones OA, Smedley J, Macallister R, Sanchez RI, Wai JS, Tan CM, Alvord WG, Hazuda DJ, Piatak M Jr, Lifson JD: Effect of SAHA administration on the residual virus pool in a model of combination antiretroviral therapy-mediated suppression in SIVmac239-infected Indian rhesus macaques. Antimicrob Agents Chemother. 2014 Sep 2. pii: AAC.03746-14. [Epub ahead of print] PMID: 25182644
  3. Sandler NG, Bosinger SE, Estes JD, Zhu RT, Tharp GK, Boritz E, Levin D, Wijeyesinghe S, Makamdop KN, Del Prete GQ, Hill BJ, Timmer JK, Reiss E, Yarden G, Darko S, Contijoch E, Todd JP, Silvestri G, Nason M, Norgren Jr RB, Keele BF, Rao S, Langer JA, Lifson JD, Schreiber G, Douek DC: Type I interferon responses in rhesus macaques prevent SIV infection and slow disease progression. Nature 511(7511):601-605, 2014. Epub 2014 Jul 9. PMID: 25043006
  4. Do T, Murphy G, Earl LA, Del Prete GQ, Grandinetti G, Estes JD, Rao P, Trubey CM, Thomas J, Li G, Spector J, Bliss D, Nath A, Lifson JD, Subramaniam S: Three-dimensional imaging of HIV-1 virological synapses reveals membrane architectures involved in virus transmission. J Virol 88(18):10327-10339, 2014. doi: 10.1128/JVI.00788-14. Epub 2014 Jun 25. PMID: 24965444
  5. Hatziioannou T, Del Prete GQ, Keele BF, Estes JD, McNatt MW, Bitzegeio J, Raymond A, Rodriguez A, Schmidt F, Mac Trubey C, Smedley J, Piatak M Jr, KewalRamani VN, Lifson JD, Bieniasz PD: HIV-1 induced AIDS in monkeys. Science 344(6190):1401-1405, 2014. doi: 10.1126/science.1250761. PMID: 24948736
  6. Del Prete GQ, Park H, Fennessey CM, Reid C, Lipkey L, Lewman L, Oswald K, Kahl C, Piatak M Jr, Quinones OA, Alvord WG, Smedley J, Estes JD, Lifson JD, Picker LJ, Keele BF: Molecularly tagged SIVmac239 synthetic swarm for tracking independent infection events. J Virol 88(14):8077-8090, 2014. doi: 10.1128/JVI.01026-14. Epub 2014 May 7. PMID: 24807714
  7. Smedley J, Turkbey IB, Bernardo ML, Del Prete GQ, Estes JD, Griffiths GL, Kobayashi H, Choyke PL, Lifson JD, Keele BF: Tracking the luminal exposure and lymphatic drainage pathways of intravaginal and intrarectal inocula used in nonhuman primate models of HIV transmission. PLoS One 9(3):e92830, 2014. doi: 10.1371/journal.pone.0092830. eCollection 2014. PMID: 24667371
  8. Shive CL, Mudd JC, Funderburg NT, Sieg SF, Kyi B, Bazdar DA, Mangioni D, Gori A, Jacobson JM, Brooks AD, Hardacre J, Ammori J, Estes JD, Schacker TW, Rodriguez B, Lederman MM: Inflammatory cytokines drive CD4 T cell cycling and impaired responsiveness to Interleukin-7: Implications for immune failure in HIV disease. J Infect Dis 2014 Feb 28. [Epub ahead of print] PMID: 24585897
  9. Sereti I, Estes JD, Thompson WL, Fischl M, Croughs T, Beq S, Lafaye de Micheaux S, Yao MD, Ober A, Wilson EMP, Natarajan V, Imamichi H, Boulassel MR, Lederman MM, Routy J-P: Decreases in colonic and systemic inflammation in chronic HIV infection after IL-7 administration. PLoS Pathog 10(1):e1003890, 2014. doi: 10.1371/journal.ppat.1003890. PMID:24497828, PMCID: PMC3907377
  10. Ault A, Tennant SM, Gorres JP, Eckhaus M, Sandler NG, Roque A, Livio S, Bao S, Foulds K, Kao S-F, Roederer M, Schmidlein P, Boyd MA, Pasetti MF, Douek DC, Estes JD, Nabel GJ, Levine MM, Rao SS: Safety and tolerability of a live oral salmonella typhimurium vaccine candidate in SIV-infected nonhuman primates. Vaccine 31(49):5879-5888, 2013. doi: 10.1016/j.vaccine.2013.09.041. Epub 2013 Oct 5. PMID: 24099872
  11. Hansen SG, Piatak M Jr, Ventura AB, Hughes CM, Gilbride RM, Ford JC, Oswald K, Shoemaker R, Li Y, Lewis MS, Gilliam AN, Xu G, Whizin N, Burwitz BJ, Planer SL, Turner JM, Legasse AW, Axthelm MK, Nelson JA, Fruh K, Sacha JB, Estes JD, Keele BF, Edlefsen PT, Lifson JD, Picker LJ: Immune clearance of highly pathogenic SIV infection. Nature 502(7469):100-104, 2013. DOI: 10.1038/nature12519. PMID: 24025770. Published: 2013-09-01
  12. Pallikkuth S, Micci L, Ende ZS, Iriele RI, Cervasi B, Lawson B, McGary CS, Rogers KA, Else JG, Silvestri G, Easley K, Estes JD, Villinger F, Pahwa S, Paiardini M: Maintenance of intestinal Th17 cells and reduced microbial translocation in SIV-infected rhesus macaques treated with Interleukin (IL)-21. PLoS Pathog 9(7): e1003471, 2013. DOI: 10.1371/journal.ppat.1003471. PMID: 23853592.
  13. Estes JD: Pathobiology of HIV/SIV-associated changes in secondary lymphoid tissues. Immunol Rev 254(1):65-77, 2013. doi: 10.1111/imr.12070. PMID:23772615
  14. Cubas RA, Mudd JC, Savoye AL, Perreau M, van Grevenynghe J, Metcalf T, Connick E, Meditz A, Freeman GJ, Abesada-Terk G Jr, Jacobson JM, Brooks AD, Crotty S, Estes JD, Pantaleo G, Lederman MM, Haddad EK: Inadequate T follicular cell help impairs B cell immunity during HIV infection. Nat Med 19(4):494-499, 2103. doi: 10.1038/nm.3109. Epub 2013 Mar 10. PMID:23475201
  15. Canary LA, Vinton CL, Morcock DR, Pierce JB, Estes JD, Brenchley JM, Klatt NR: Rate of AIDS progression is associated with gastrointestinal dysfunction in simian immunodeficiency virus-infected pigtail macaques. J Immunol 190(6):2959-2965, 2013. doi:10.4049/jimmunol.1202319. Epub 2013 Feb 11. PMID: 23401593
  16. Klatt NR, Canary LA, Sun X, Vinton CL, Funderburg NT, Morcock DR, Quiñones M, Deming CB, Perkins M, Hazuda DJ, Miller MD, Lederman MM, Segre JA, Lifson JD, Haddad EK, Estes JD, Brenchley JM: Probiotic/prebiotic supplementation of antiretrovirals improves gastrointestinal immunity in SIV-infected macaques. J Clin Invest 123(2):903-907, 2013. 2013 Jan 16. doi:pii: 66227. 10.1172/JCI66227. PMID: 23321668
  17. Tabb B, Morcock DR, Trubey CM, Quiñones OA, Hao XP, Smedley J, Macallister R, Piatak M Jr, Harris LD, Paiardini M, Silvestri G, Brenchley JM, Alvord WG, Lifson JD, Estes JD: Reduced inflammation and lymphoid tissue immunopathology in rhesus macaques receiving anti-tumor necrosis factor treatment during primary simian immunodeficiency virus infection. J Infect Dis 207(6):880-892, 2013 doi: 10.1093/infdis/jis643. Epub 2012 Oct 19. PMID: 23087435
  18. Brenchley JM, Vinton C, Tabb B, Hao XP, Connick E, Paiardini M, Lifson JD, Silvestri G, Estes JD: Differential infection patterns of CD4+ T cells and lymphoid tissue viral burden distinguish progressive and nonprogressive lentiviral infections. Blood 120(20):4172-4181, 2012. doi: 10.1182/blood-2012-06-437608. Epub 2012 Sep 18. PMID: 22990012
  19. Micci L, Cervasi B, Ende ZS, Iriele RI, Reyes-Aviles E, Vinton C, Else J, Silvestri G, Ansari AA, Villinger F, Pahwa S, Estes JD, Brenchley JM, Paiardini M: Paucity of IL-21-producing CD4+ T cells is associated with Th17 cell depletion in SIV infection of rhesus macaques. Blood 120(19):3925-3935, 2012. doi:10.1182/blood-2012-04-420240. Epub 2012 Sep 18. PMID: 22990011
  20. Klatt NR, Estes JD, Sun X, Ortiz AM, Barber JS, Harris LD, Cervasi B, Yokomizo LK, Pan L, Vinton CL, Tabb B, Canary LA, Dang Q, Hirsch VM, Alter G, Belkaid Y, Lifson JD, Silvestri G, Milner JD, Paiardini M, Haddad EK, Brenchley JM: Loss of mucosal CD103+ DCs and IL-17+ and IL-22+ lymphocytes is associated with mucosal damage in SIV infection. Mucosal Immunol 5(6):646-657, 2012. doi: 10.1038/mi.2012.38. Epub 2012 May 30. PMID: 22643849
  21. Estes JD: Enhancing immune responses to limit chronic immune activation during SIV. J Clin Invest 122(5):1611-1614, 2012. doi: 10.1172/JCI63389. Epub 2012 Apr 23. PMID: 22523060
  22. Del Prete GQ, Kearney MF, Spindler J, Wiegand A, Chertova E, Roser JD, Estes JD, Hao XP, Trubey CM, Lara A, Lee K, Chaipan C, Bess JW Jr, Nagashima K, Keele BF, Pung R, Smedley J, Pathak VK, Kewalramani VN, Coffin JM, Lifson JD: Restricted replication of xenotropic murine leukemia virus-related virus in pigtailed macaques. J Virol 86(6):3152-3166, 2012. Epub 2012 Jan 11. PMID: 22238316

Staffing – Retroviral Immunopathology Section

  • Claire Deleage, Ph.D., Postdoctoral Fellow
  • Carissa Lucero, Ph.D., Postdoctoral Fellow
  • David Morcock, M.S., Research Associate II
  • Xing-Pei (Harry) Hao, Dedicated PHL Support

Staffing – Tissue Analysis Core

  • Leslie A. Johnston, Research Associate, II