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.
Harper J, Gordon S, Chan CN, Wang H, Lindemuth E, Galardi C, Falcinelli SD, Raines SLM, Read JL, Nguyen K, McGary CS, Nekorchuk M, Busman-Sahay K, … Estes JD, Paiardini M. CTLA-4 and PD-1 dual blockade induces SIV reactivation without control of rebound after antiretroviral therapy interruption. Nature Medicine, 2020
Webb GM, Molden J, Busman-Sahay K, … Estes JD, Skinner PJ, Sacha JB. The human IL-15 superagonist N-803 promotes migration of virus-specific CD8+ T and NK cells to B cell follicles but does not reverse latency in ART-suppressed, SHIV-infected macaques. PLoS Pathogens, 2020
McBrien JB, Mavigner M, Franchitti L, Smith SA, White E, Tharp GK, Walum H, Busman-Sahay K, … Estes JD, Derdeyn CA, Garcia JV, Kulpa DA, Chahroudi A, Silvestri G. Robust and persistent reactivation of SIV and HIV by N-803 and depletion of CD8+ cells. Nature, 2020
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, … Schacker TW. Defining total-body AIDS-virus burden with implications for curative strategies. Nature Medicine, 2017
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.
Abdel-Mohsen M, … Estes JD, Hope TJ, Kostman J, Mounzer K, Caskey M, Fox L, Frank I, Riley JL, Tebas P, Montaner LJ; BEAT-HIV Delaney Collaboratory to Cure HIV-1 infection. Recommendations for measuring HIV reservoir size in cure-directed clinical trials. Nature Medicine, 2020 (Perspective)
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 (Review)
Deleage C, Wietgrefe SW, Del Prete G, Morcock DR, Hao XP, … Estes JD. Defining HIV and SIV Reservoirs in Lymphoid Tissues. Pathogens and Immunity, 2016
Estes JD, LeGrand R, Petrovas C. Visualizing the Immune System: Providing Key Insights into HIV/SIV Infections. Frontiers in Immunology, 2018 (Review)
Petrovas C, Ferrando-Martinez S, Gerner MY, Casazza JP, Pegu A, Deleage C, … 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. Science Translational Medicine, 2017
Moysi E, Estes JD, Petrovas C. Novel Imaging Methods for Analysis of Tissue Resident Cells in HIV/SIV. Current HIV/AIDS Reports, 2016 (Review)
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.
Raehtz KD, Barrenäs F, Xu C, Busman-Sahay K, … Estes JD, Apetrei C, Pandrea I. African green monkeys avoid SIV disease progression by preventing intestinal dysfunction and maintaining mucosal barrier integrity. PLoS Pathogens, 2020
Mudd JC, Busman-Sahay K, DiNapoli SR, Lai S, Sheik V, Lisco A, Deleage C, … Estes JD, Brenchley JM. Hallmarks of primate lentiviral immunodeficiency infection recapitulate loss of innate lymphoid cells. Nature Communications, 2018
Wang Y, Lifshitz L, Gellatly K, Vinton CL, Busman-Sahay K, … Estes JD, Brenchley JM, Garber M, Deeks SG, Luban J. HIV-1-induced cytokines deplete homeostatic innate lymphoid cells and expand TCF7-dependent memory NK cells. Nature Immunology, 2020
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. Nature Medicine, 2018
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. Journal of Infectious Disease, 2013
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 Pathogens, 2010
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.
McQueen P, Busman-Sahay K, Rieder F, Noël-Romas L, McCorrister S, Westmacott G, Estes JD, Burgener A. Intestinal proteomic analysis of a novel non-human primate model of experimental colitis reveals signatures of mitochondrial and metabolic dysfunction. Mucosal Immunology, 2019
Hao XP, Lucero CM, Turkbey B, Bernardo ML, Morcock DR, Deleage C, … Estes JD. Experimental colitis in SIV-uninfected rhesus macaques recapitulates important features of pathogenic SIV infection. Nature Communications, 2015
Exploring vaccination strategies and drug repurposing to target SARS-CoV-2
Aid M, Busman-Sahay K, Vidal SJ, Maliga Z, Bondoc S, Starke C, Terry M, … Estes JD, Barouch DH. Vascular Disease and Thrombosis in SARS-CoV-2-Infected Rhesus Macaques. Cell, 2020
Hoang TN, Pino M, Boddapati AK, Viox EG, Starke CE, Upadhyay AA, Gumber S, Nekorchuk M, Busman-Sahay K, … Estes JD, Vanderford TH, Schinazi RF, Bosinger SE, Paiardini M. Baricitinib treatment resolves lower airway macrophage inflammation and neutrophil recruitment in SARS-CoV-2-infected rhesus macaques. Cell, 2020
Tostanoski LH, Wegmann F, Martinot AJ, Loos C, McMahan K, Mercado NB, Yu J, Chan CN, Bondoc S, Starke CE, Nekorchuk M, Busman-Sahay K, … Estes JD, Schuitemaker H, Zahn R, Barouch DH. Ad26 vaccine protects against SARS-CoV-2 severe clinical disease in hamsters. Nature Medicine, 2020
Chandrashekar A, Liu J, Martinot AJ, McMahan K, Mercado NB, Peter L, Tostanoski LH, Yu J, Maliga Z, Nekorchuk M, Busman-Sahay K, Terry M, … Estes JD, Andersen H, Lewis MG, Barouch DH. SARS-CoV-2 infection protects against rechallenge in rhesus macaques. Science, 2020
Brook OR, Piper KG, Mercado NB, Gebre MS, Barouch DH, Busman-Sahay K, Starke CE, Estes JD, Martinot AJ, Wrijil L, Ducat S, Hecht JL. Feasibility and safety of ultrasound-guided minimally invasive autopsy in COVID-19 patients.Abdominal Radiology, 2020