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Human T cells play a central role in the human response to tuberculosis and in efforts to develop better vaccines. For decades, it was thought that T cells only that recognize antigens in the context of a diverse array of presentation molecules such that an epitope could be considered private, or restricted to each patient or human donor. Therefore, broad detection or alteration of T cell responses to one kind of antigen in all humans was viewed as technologically impossible. Over the past decade “Donor Unrestricted T cells” (DURT) that recognize their antigens through highly conserved molecules that are present among all humans have been discovered. The CTVD DURT research community seeks to harness these donor unrestricted T cell responses to MR1, CD1 and HLA-E proteins for improved vaccines against TB.

The DURT research community is comprised of individuals from different Institutions worldwide and includes the following members:​​


Dr Tom Ottenhoff

Co-Chair

My mission is to dissect immunological and host-genetic mechanisms of protective and pathologic immunity to mycobacterial infections, in order to design more effective intervention strategies, including novel vaccination strategies, innovative diagnostics and anti-microbial treatments.

Tuberculosis research is a major theme in my research programs. This work is fundamental, preclinical, translational as well as clinical in nature. Our efforts aim to develop better vaccines, as well as diagnostic, immunologic, transcriptomic and metabolic “biomarker signatures”. My group's work has led to a number of first-in-man clinical studies with new, molecularly defined synthetic TB vaccines. Systems biology, chemical genetics, transcriptomics, metabolomics and immunomics approaches are used to identify key cellular signalling pathways in host defense to intracellular pathogens in general, and M. tuberculosis and Salmonellae in particular. Correlates of protection and prospective correlates of risk of developing TB are being identified. Moreover, there is strong interest in co-infections (Helminth-infections; HIV) and co-morbidities including type-2 diabetes, a major TB-risk factor. Using technologies developed in the TB research program, recent work also enabled identification of biomarkers of Ebola-vaccine induced human responses. Extensive international collaborative networks have been established, which include leading partners from EU, US and TB endemic areas/countries. Host-directed therapeutic targets and compounds are being studied aiming a improved, adjunct treatment for TB, including DR-TB.​

Co-chair

Chetan Seshadri

Dr. Seshadri is Associate Professor in the Division of Allergy and Infectious Disease at the University of Washington. He studied biomedical engineering as an undergraduate at Rutgers University in NJ and then attended New Jersey Medical School. As a medical resident at Duke University, he conducted field-based research in HIV and TB co-infection in Tanzania. He then spent a year working for Doctors Without Borders in Malawi. He completed his clinical infectious diseases fellowship at the Massachusetts General Hospital and then joined Branch Moody’s lab as a post-doctoral fellow. He moved to Seattle in 2009 and joined Tom Hawn’s lab to pursue a second post-doc in human genetics. In 2013 he started his own lab, which is using approaches in human genetics and immunology to understand the importance of lipid-specific T cells.


Members

John Altman

Erin Adams
Yueh-Hsiu Chien
Dan Hoft​
Mitch Kronenberg​
Dave Lewinsohn
Branch Moody
Jonah Sacha
​Steffen Stenger
​Emmanuel Treiner
Ildiko Van Rhijn ​