Daniel Douek, M.D., Ph.D.

Human Immunology Section

Major Areas of Research

  • HIV disease acquisition and pathogenesis
  • Inflammation and the microbiome
  • Immune repertoire analysis and vaccine correlates
  • Preparedness against pandemic threats

Featured Research Program

Program Description

The Human Immunology Section (HIS) studies the processes that determine the course of human diseases in which the immune system plays a central role in their pathogenesis and outcome. We take a systems biology approach to generate multi-scale datasets. Our overriding philosophy is to address questions of human disease directly in humans and use the knowledge gained to initiate clinical studies of new therapeutic and vaccine approaches.

Our studies of HIV explore the cellular and molecular mechanisms by which the virus is acquired and disease progression is maintained, with an emphasis on host genetic and microbiological factors that render an individual vulnerable to infection. We explore the relationships among target cell types and availability as the reservoir for HIV, systemic inflammation, lymphoid tissue architecture, the gastrointestinal mucosal barrier and the individual's 'pathogen burden' in determining the rate of disease progression. We extend our understanding of the relationship between the host microbiome, systemic inflammation and immune system functionality to other infectious and non-infectious disease states and responses to vaccination.

Another major aspect of our work is to explore T cell and B cell receptor repertoire diversity in infectious disease and cancer. We have pioneered methods for next-generation sequencing and bioinformatic analysis of TCR and Ig repertoires, and high throughput isolation and functional testing of antigen-specific TCRs and Igs.

The laboratory is also performing virus discovery and global immune analysis of targeted human cohorts to detect reactivity against viruses which are potential pandemic threats. The premise of this project is to use virologic and immunologic screening for the discovery of tangible immunobiological countermeasures and to provide a platform to pre-emptively generate reagent and data resources for early detection and diagnosis.
 

Biography

Daniel Douek, M.D., Ph.D., is the Chief of the Genome Analysis Core (GAC). The GAC was established to develop and perform innovative sequencing techniques specifically targeted at immune respertoire analysis. These sequencing technologies are also being used to evaluate candidates for other vaccines, such as influenza and respiratory syncyticial virus, including those undertaken with VRC intra- and extramural collaborators.

Daniel Douek, M.D., Ph.D., is also the Chief of the Human Immunology Section (HIS). HIS studies the processes that determine the course of human diseases in which the immune system plays a central role in their pathogenesis and outcome. Our overriding philosophy is to address questions of human disease directly in humans. 

Selected Publications

Nganou-Makamdop K, Talla A, Sharma AA, Darko S, Ransier A, Laboune F, Chipman JG, Beilman GJ, Hoskuldsson T, Fourati S, Schmidt TE, Arumugam S, Lima NS, Moon D, Callisto S, Schoephoerster J, Tomalka J, Mugyenyi P, Ssali F, Muloma P, Ssengendo P, Leda AR, Cheu RK, Flynn JK, Morou A, Brunet-Ratnasingham E, Rodriguez B, Lederman MM, Kaufmann DE, Klatt NR, Kityo C, Brenchley JM, Schacker TW, Sekaly RP, Douek DC. Translocated microbiome composition determines immunological outcome in treated HIV infection. Cell. 2021 Jun 30;S0092-8674(21)00653-X.

Boritz EA, Darko S, Swaszek L, Wolf G, Wells D, Wu X, Henry AR, Laboune F, Hu J, Ambrozak D, Hughes MS, Hoh R, Casazza JP, Vostal A, Bunis D, Nganou-Makamdop K, Lee JS, Migueles SA, Koup RA, Connors M, Moir S, Schacker T, Maldarelli F, Hughes SH, Deeks SG, Douek DC. Multiple Origins of Virus Persistence during Natural Control of HIV Infection. Cell. 2016 Aug 11;166(4):1004-15.

Sandler NG, Bosinger SE, Estes JD, Zhu RTR, Tharp GK, Boritz E, Levin D, Wijeyesinghe S, Nganou Makamdop K, del Prete GQ, Hill BJ, Timmer JK, Reiss E, Yarden G, Darko S, Contijoch E, Todd JP, Silvestri G, Nason M, Norgren RB Jr., Keele BF, Rao S, Langer JA, Lifson JD, Schreiber G and Douek DC. Type I IFN responses in rhesus macaques prevent SIV infection and slow disease progression. Nature. 2014 Jul 31;511(7511):601-5.

Milner JD, Brenchley JM, Laurence A, Freeman AF, Hill BJ, Elias KM, Kanno Y, Spalding C, Elloumi HZ, Paulson ML, Davis J, Hsu A, Asher AI, O'Shea J, Holland SM, Paul WE, Douek DC. Impaired T(H)17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome. Nature. 2008 Apr 10;452(7188):773-6.

Brenchley JM, Price DA, Schacker TW, Asher TE, Silvestri G, Rao S, Kazzaz Z, Bornstein E, Lambotte O, Altmann D, Blazar BR, Rodriguez B, Teixeira-Johnson L, Landay A, Martin JN, Hecht FM, Picker LJ, Lederman MM, Deeks SG, Douek DC. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med. 2006 Dec;12(12):1365-71.

Douek DC, McFarland RD, Keiser PH, Gage EA, Massey JM, Haynes BF, Polis MA, Haase AT, Feinberg MB, Sullivan JL, Jamieson BD, Zack JA, Picker LJ, Koup RA. Changes in thymic function with age and during the treatment of HIV infection. Nature. 1998 Dec 17;396(6712):690-5.

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