Jacob D. Estes, Ph.D.

Uncontrolled inflammation generates significant morbidity and mortality in many non-infectious (e.g. inflammatory bowel disease) and infectious (e.g. HIV) diseases. The central focus of Dr. Estes's research seeks to understand how immune response dysregulation leads to tissue pathology, disease progression, and in the context of infectious diseases, pathogen persistence with the goal to develop and test effective therapeutic strategies that prevent disease and restores immune function. Towards that end, we utilize non-human primate models of several highly relevant human diseases, with a strong emphasis on models of HIV infection and disease, to elucidate determinants of local and systemic inflammation and to test therapeutics that modulate the immune landscape, restore immune homeostasis, and reduce viral reservoirs. We capitalize on the full power of our pre-clinical models by performing cutting-edge in vivo and in situ tissue analyses, including our pioneering work with next-generation in situ hybridization and immunohistochemistry, to generate comprehensive characterizations of the host-pathogen interactions, including the cellular and inflammatory immune landscapes present within relevant tissue microenvironments. Our studies invite collaboration, and we work with academic, government and industry partners around the globe on a wide range of projects from intestinal dysbiosis to the distribution of Zika virus within the host.

Current projects in the laboratory include:

  1. The contribution of GI tract epithelial barrier dysfunction and damage to local and systemic inflammation during HIV/SIV infection, and subsequent tissue pathology and viral reservoir persistence. Moreover, we are testing the therapeutic administration of novel immune modulating agents, in collaboration with industry partners, to target proinflammatory cytokines in order to restore GI tract immune homeostasis and mitigate pathology.
  2. Characterization of the HIV/SIV reservoirs in pharmacologic "sanctuary" sites such as lymphoid tissue B cell follicles, gut associated lymphoid tissues, and the central nervous system, with a two-pronged goal of understanding the factors that contribute to HIV/SIV persistence and developing novel therapies to reduce the size of the reservoir as part of the broader HIV cure strategy.
  3. Elucidating mechanisms controlling inflammatory bowel disease and intestinal fibrosis to identify original therapeutic targets, by utilizing the first nonhuman primate model of experimental acute and chronic colitis in conjunction with a novel, non-invasive MRI-based method for quantifying intestinal inflammation and disease progression.
  4. The development of new, sensitive in vivo and in situ tissue visualization techniques to advance our understanding of pathogen persistence and tissue pathology.


Dr. Estes graduated from Brigham Young University with a B.S. in Microbiology and Molecular Biology in 1999. He continued his graduate education at Brigham Young University and obtained his Ph.D. in Immunology and HIV Pathogenesis in 2003 in the laboratory of Dr. Gregory Burton. From 2003 to 2007, he was 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 immunopathology of lentiviral infections. Following postdoctoral training, Dr. Estes joined the AIDS and Cancer Virus Program at the Frederick National Laboratory for Cancer Research, and was a Principal Investigator of the Retroviral Immunopathology Section and Senior Principal Scientist and Head of the Tissue Analysis Core. Dr. Estes was appointed an Adjunct Professor in the School of Health and Biomedical Sciences in the College of Science, Engineering and Health at RMIT University in Melbourne, Australia in 2017. In 2017, Dr. Estes accepted a dual appointment as Professor within the Vaccine and Gene Therapy Institute (VGTI) and Chief of the Division of Pathobiology &Immunology in the Oregon National Primate Research Center (ONPRC) at OHSU.

Lab members

  • Kathleen Busman-Sahay, Ph.D.
  • Chi Ngai Chan, Ph.D.
  • Leslie Johnston, B.S.
  • Michael Nekorchuk, Ph.D.

Select publications

  • Ortiz AM, Flynn JK, DiNapoli SR, Vujkovic-Cvijin I, Starke CE, Lai SH, Long ME, Sortino O, Vinton CL, Mudd JC, Johnston L, Busman-Sahay K, Belkaid Y, Estes JD, Brenchley JM. Experimental microbial dysbiosis does not promote disease progression in SIV-infected macaques. Nat Med. 2018 Jul 30. doi: 10.1038/s41591-018-0132-5. [Epub ahead of print] PubMed PMID: 30061696.
  • Marshall VA, Labo N, Hao XP, Holdridge B, Thompson M, Miley W, Brands C, Coalter V, Kiser R, Anver M, Golubeva Y, Warner A, Jaffe ES, Piatak M Jr, Wong SW, Ohlen C, MacAllister R, Smedley J, Deleage C, Del Prete GQ, Lifson JD, Estes JD, Whitby D. Gammaherpesvirus infection and malignant disease in rhesus macaques experimentally infected with SIV or SHIV. PLoS Pathog. 2018 Jul 12;14(7):e1007130. doi: 10.1371/journal.ppat.1007130. eCollection 2018 Jul. PubMed PMID: 30001436; PubMed Central PMCID: PMC6042791.
  • Estes JD, Wong SW, Brenchley JM. Nonhuman primate models of human viral infections. Nat Rev Immunol. 2018 Jun;18(6):390-404. doi: 10.1038/s41577-018-0005-7. Review. PubMed PMID: 29556017; PubMed Central PMCID: PMC5970954.
  • Peterson CW, Wang J, Deleage C, Reddy S, Kaur J, Polacino P, Reik A, Huang ML, Jerome KR, Hu SL, Holmes MC, Estes JD, Kiem HP. Differential impact of transplantation on peripheral and tissue-associated viral reservoirs: Implications for HIV gene therapy. PLoS Pathog. 2018 Apr 19;14(4):e1006956. doi: 10.1371/journal.ppat.1006956. eCollection 2018 Apr. PubMed PMID: 29672640; PubMed Central PMCID: PMC5908070.
  • Estes JD, LeGrand R, Petrovas C. Visualizing the Immune System: Providing Key  Insights into HIV/SIV Infections. Front Immunol. 2018 Mar 2;9:423. doi: 10.3389/fimmu.2018.00423. eCollection 2018. Review. PubMed PMID: 29552017; PubMed Central PMCID: PMC5840205.
  • Deleage C, Chan CN, Busman-Sahay K, Estes JD. Next-generation in situ hybridization approaches to define and quantify HIV and SIV reservoirs in tissue  microenvironments. Retrovirology. 2018 Jan 9;15(1):4. doi: 10.1186/s12977-017-0387-9. Review. PubMed PMID: 29316956; PubMed Central PMCID: PMC5761108.
  • Estes JD, Kityo C, Ssali F, Swainson L, Makamdop KN, Del Prete GQ, Deeks SG, Luciw PA, Chipman JG, Beilman GJ, Hoskuldsson T, Khoruts A, Anderson J, Deleage C, Jasurda J, Schmidt TE, Hafertepe M, Callisto SP, Pearson H, Reimann T, Schuster J, Schoephoerster J, Southern P, Perkey K, Shang L, Wietgrefe SW, Fletcher CV, Lifson JD, Douek DC, McCune JM, Haase AT, Schacker TW. Defining total-body AIDS-virus burden with implications for curative strategies. Nat Med. 2017 Nov;23(11):1271-1276. doi: 10.1038/nm.4411. Epub 2017 Oct 2. PubMed PMID: 28967921; PubMed Central PMCID: PMC5831193.
  • McGary CS, Deleage C, Harper J, Micci L, Ribeiro SP, Paganini S, Kuri-Cervantes L, Benne C, Ryan ES, Balderas R, Jean S, Easley K, Marconi V, Silvestri G, Estes JD, Sekaly RP, Paiardini M. CTLA-4(+)PD-1(-) Memory CD4(+) T Cells Critically Contribute to Viral Persistence in Antiretroviral Therapy-Suppressed, SIV-Infected Rhesus Macaques. Immunity. 2017 Oct 17;47(4):776-788.e5. doi: 10.1016/j.immuni.2017.09.018. PubMed PMID: 29045906; PubMed Central PMCID: PMC5679306.
  • Petrovas C, Ferrando-Martinez S, Gerner MY, Casazza JP, Pegu A, Deleage C,
    Cooper A, Hataye J, Andrews S, Ambrozak D, Del Río Estrada PM, Boritz E, Paris R, Moysi E, Boswell KL, Ruiz-Mateos E, Vagios I, Leal M, Ablanedo-Terrazas Y, Rivero A, Gonzalez-Hernandez LA, McDermott AB, Moir S, Reyes-Terán G, Docobo F, Pantaleo G, Douek DC, Betts MR, Estes JD, Germain RN, Mascola JR, Koup RA. Follicular CD8  T cells accumulate in HIV infection and can kill infected cells in vitro via bispecific antibodies. Sci Transl Med. 2017 Jan 18;9(373). pii: eaag2285. doi: 10.1126/scitranslmed.aag2285. PubMed PMID: 28100833; PubMed Central PMCID: PMC5497679.
  • Osuna CE, Lim SY, Deleage C, Griffin BD, Stein D, Schroeder LT, Omange RW, Best K, Luo M, Hraber PT, Andersen-Elyard H, Ojeda EF, Huang S, Vanlandingham DL, Higgs S, Perelson AS, Estes JD, Safronetz D, Lewis MG, Whitney JB. Zika viral dynamics and shedding in rhesus and cynomolgus macaques. Nat Med. 2016 Dec;22(12):1448-1455. doi: 10.1038/nm.4206. Epub 2016 Oct 3. Erratum in: Nat Med. 2017 Feb 7;23 (2):264. PubMed PMID: 27694931; PubMed Central PMCID: PMC5293594.
  • Leong YA, Chen Y, Ong HS, Wu D, Man K, Deleage C, Minnich M, Meckiff BJ, Wei  Y, Hou Z, Zotos D, Fenix KA, Atnerkar A, Preston S, Chipman JG, Beilman GJ, Allison CC, Sun L, Wang P, Xu J, Toe JG, Lu HK, Tao Y, Palendira U, Dent AL, Landay AL, Pellegrini M, Comerford I, McColl SR, Schacker TW, Long HM, Estes JD,  Busslinger M, Belz GT, Lewin SR, Kallies A, Yu D. CXCR5(+) follicular cytotoxic T cells control viral infection in B cell follicles. Nat Immunol. 2016 Oct;17(10):1187-96. doi: 10.1038/ni.3543. Epub 2016 Aug 3. PubMed PMID: 27487330.
  • Deleage C, Wietgrefe SW, Del Prete G, Morcock DR, Hao XP, Piatak M Jr, Bess J, Anderson JL, Perkey KE, Reilly C, McCune JM, Haase AT, Lifson JD, Schacker TW, Estes JD. Defining HIV and SIV Reservoirs in Lymphoid Tissues. Pathog Immun. 2016 Spring;1(1):68-106. PubMed PMID: 27430032; PubMed Central PMCID: PMC4943335.
  • Ortiz AM, Klase ZA, DiNapoli SR, Vujkovic-Cvijin I, Carmack K, Perkins MR, Calantone N, Vinton CL, Riddick NE, Gallagher J, Klatt NR, McCune JM, Estes JD, Paiardini M, Brenchley JM. IL-21 and probiotic therapy improve Th17 frequencies, microbial translocation, and microbiome in ARV-treated, SIV-infected macaques. Mucosal Immunol. 2016 Mar;9(2):458-67. doi: 10.1038/mi.2015.75. Epub 2015 Aug 19. PubMed PMID: 26286233; PubMed Central PMCID: PMC4760912.
  • Moysi E, Estes JD, Petrovas C. Novel Imaging Methods for Analysis of Tissue Resident Cells in HIV/SIV. Curr HIV/AIDS Rep. 2016 Feb;13(1):38-43. doi: 10.1007/s11904-016-0300-5. Review. PubMed PMID: 26830285.
  • Hao XP, Lucero CM, Turkbey B, Bernardo ML, Morcock DR, Deleage C, Trubey CM, Smedley J, Klatt NR, Giavedoni LD, Kristoff J, Xu A, Del Prete GQ, Keele BF, Rao SS, Alvord WG, Choyke PL, Lifson JD, Brenchley JM, Apetrei C, Pandrea I, Estes JD. Experimental colitis in SIV-uninfected rhesus macaques recapitulates important features of pathogenic SIV infection. Nat Commun. 2015 Aug 18;6:8020. doi: 10.1038/ncomms9020. PubMed PMID: 26282376; PubMed Central PMCID: PMC4544774.
  • Estes JD, Reilly C, Trubey CM, Fletcher CV, Cory TJ, Piatak M Jr, Russ S, Anderson J, Reimann TG, Star R, Smith A, Tracy RP, Berglund A, Schmidt T, Coalter V, Chertova E, Smedley J, Haase AT, Lifson JD, Schacker TW. Antifibrotic therapy  in simian immunodeficiency virus infection preserves CD4+ T-cell populations and  improves immune reconstitution with antiretroviral therapy. J Infect Dis. 2015 Mar 1;211(5):744-54. doi: 10.1093/infdis/jiu519. Epub 2014 Sep 22. PubMed PMID: 25246534; PubMed Central PMCID: PMC4334805.
  • Fukazawa Y, Lum R, Okoye AA, Park H, Matsuda K, Bae JY, Hagen SI, Shoemaker R, Deleage C, Lucero C, Morcock D, Swanson T, Legasse AW, Axthelm MK, Hesselgesser J, Geleziunas R, Hirsch VM, Edlefsen PT, Piatak M Jr, Estes JD, Lifson JD, Picker LJ. B cell follicle sanctuary permits persistent productive simian immunodeficiency virus infection in elite controllers. Nat Med. 2015 Feb;21(2):132-9. doi: 10.1038/nm.3781. Epub 2015 Jan 19. PubMed PMID: 25599132; PubMed Central PMCID: PMC4320022.
  • Somsouk M, Estes JD, Deleage C, Dunham RM, Albright R, Inadomi JM, Martin JN, Deeks SG, McCune JM, Hunt PW. Gut epithelial barrier and systemic inflammation during chronic HIV infection. AIDS. 2015 Jan 2;29(1):43-51. doi: 10.1097/QAD.0000000000000511. PubMed PMID: 25387317; PubMed Central PMCID: PMC4444362.
  • Estes JD. Pathobiology of HIV/SIV-associated changes in secondary lymphoid tissues. Immunol Rev. 2013 Jul;254(1):65-77. doi: 10.1111/imr.12070. Review. PubMed PMID: 23772615; PubMed Central PMCID: PMC6066369.
  • 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. 2013 Mar 15;207(6):880-92. doi: 10.1093/infdis/jis643. Epub 2012 Oct 19. PubMed PMID: 23087435; PubMed Central PMCID: PMC3571439.
  • 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. 2013 Feb;123(2):903-7. doi: 10.1172/JCI66227. Epub 2013 Jan 16. PubMed PMID: 23321668; PubMed Central PMCID: PMC3561826.
  • 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. 2012 Nov 15;120(20):4172-81. doi: 10.1182/blood-2012-06-437608. Epub 2012 Sep 18. Erratum in: Blood. 2014 Jun 26;123(26):4152. PubMed PMID: 22990012; PubMed Central PMCID: PMC3501715.
  • Keele BF, Estes JD. Barriers to mucosal transmission of immunodeficiency viruses. Blood. 2011 Jul 28;118(4):839-46. doi: 10.1182/blood-2010-12-325860. Epub 2011 May 9. Review. PubMed PMID: 21555745; PubMed Central PMCID: PMC3148165.
  • 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. 2010 Aug 19;6(8):e1001052. doi: 10.1371/journal.ppat.1001052. PubMed PMID: 20808901; PubMed Central PMCID: PMC2924359.
  • Li Q, Estes JD, Schlievert PM, Duan L, Brosnahan AJ, Southern PJ, Reilly CS,  Peterson ML, Schultz-Darken N, Brunner KG, Nephew KR, Pambuccian S, Lifson JD, Carlis JV, Haase AT. Glycerol monolaurate prevents mucosal SIV transmission. Nature. 2009 Apr 23;458(7241):1034-8. doi: 10.1038/nature07831. Epub 2009 Mar 4.  PubMed PMID: 19262509; PubMed Central PMCID: PMC2785041.
  • Estes JD. Role of collagen deposition in lymphatic tissues and immune reconstruction during HIV-1 and SIV infections. Curr HIV/AIDS Rep. 2009 Feb;6(1):29-35. Review. PubMed PMID: 19149994.
  • Estes JD, Gordon SN, Zeng M, Chahroudi AM, Dunham RM, Staprans SI, Reilly CS, Silvestri G, Haase AT. Early resolution of acute immune activation and induction of PD-1 in SIV-infected sooty mangabeys distinguishes nonpathogenic from pathogenic infection in rhesus macaques. J Immunol. 2008 May 15;180(10):6798-807. PubMed PMID: 18453600; PubMed Central PMCID: PMC2596686.
  • Li Q, Estes JD, Duan L, Jessurun J, Pambuccian S, Forster C, Wietgrefe S, Zupancic M, Schacker T, Reilly C, Carlis JV, Haase AT. Simian immunodeficiency virus-induced intestinal cell apoptosis is the underlying mechanism of the regenerative enteropathy of early infection. J Infect Dis. 2008 Feb 1;197(3):420-9. doi: 10.1086/525046. PubMed PMID: 18199035.
  • Estes JD, Wietgrefe S, Schacker T, Southern P, Beilman G, Reilly C, Milush JM, Lifson JD, Sodora DL, Carlis JV, Haase AT. Simian immunodeficiency virus-induced lymphatic tissue fibrosis is mediated by transforming growth factor beta 1-positive regulatory T cells and begins in early infection. J Infect Dis. 2007 Feb 15;195(4):551-61. Epub 2007 Jan 8. PubMed PMID: 17230415.
  • Estes JD, Li Q, Reynolds MR, Wietgrefe S, Duan L, Schacker T, Picker LJ, Watkins DI, Lifson JD, Reilly C, Carlis J, Haase AT. Premature induction of an immunosuppressive regulatory T cell response during acute simian immunodeficiency virus infection. J Infect Dis. 2006 Mar 1;193(5):703-12. Epub 2006 Jan 30. PubMed PMID: 16453267.
  • Li Q, Duan L, Estes JD, Ma ZM, Rourke T, Wang Y, Reilly C, Carlis J, Miller CJ, Haase AT. Peak SIV replication in resting memory CD4+ T cells depletes gut lamina propria CD4+ T cells. Nature. 2005 Apr 28;434(7037):1148-52. PubMed PMID: 15793562.
  • Estes JD, Thacker TC, Hampton DL, Kell SA, Keele BF, Palenske EA, Druey KM, Burton GF. Follicular dendritic cell regulation of CXCR4-mediated germinal center CD4 T cell migration. J Immunol. 2004 Nov 15;173(10):6169-78. PubMed PMID: 15528354.
  • Estes JD, Keele BF, Tenner-Racz K, Racz P, Redd MA, Thacker TC, Jiang Y, Lloyd MJ, Gartner S, Burton GF. Follicular dendritic cell-mediated up-regulation of CXCR4 expression on CD4 T cells and HIV pathogenesis. J Immunol. 2002 Sep 1;169(5):2313-22. PubMed PMID: 12193696.