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

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.