Jacob Estes

  • Professor, VGTI-Vaccine and Gene Therapy Institute
  • Chief, Division of Pathobiology & Immunology, Oregon National Primate Research Center

Biography

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. Characterizing HIV/SIV reservoirs in pharmacologic "sanctuary" sites such as 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.

2. Developing and applying cutting-edge in situ multiplex spatial imaging techniques to advance our understanding of pathogen dissemination and persistence, as well as concomitant tissue pathology, especially during latent and active HIV and Mycobacterium tuberculosis infection.

3. Dampening GI-associated inflammation during HIV/SIV infection to mitigate tissue pathology and decrease viral reservoir persistence via therapeutic administration of novel immune modulating agents, in collaboration with industry partners.

4. Elucidating mechanisms controlling inflammatory bowel disease and intestinal fibrosis by utilizing the first nonhuman primate pre-clinical model of experimental acute and chronic colitis to identify and, ultimately, target novel therapeutic pathways.

Biography:

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. Scientific Program Manager
- Margaret Terry Laboratory Program Manager
- Chi Ngai Chan, Ph.D.
- Michael Nekorchuk, Ph.D.
- Stephen Bondoc, HLT(ASCP)
- Carly E. Starke, Ph.D.
- Madelyne Burcher
- Skyler Younger
- Jason Plyler, M.S.2
- Rachel Dannay

Education

  • Ph.D., 2003, Brigham Young University

Areas of interest

  • HIV/SIV immunopathology, reservoir persistence, inflammatory bowel disease, and lymphoid and intestinal fibrosis

Publications

Selected 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; PubMe
  • 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):127
  • 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 vi
  • 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.

Publications

  • {{ pub.journalAssociation.journal.name.text[0].value }}