Professor Ottenhof is full Professor in Immunology, in particular the immunology and Immunogenetics of mycobacterial infectious diseases. He is also Head Laboratory of the Dept. of Infectious Diseases and Head of the Group Immunology and Immunogenetics of Bacterial Infectious Diseases.

More information about Thomas Ottenhoff

Professor Ottenhof is full Professor in Immunology, in particular the immunology and Immunogenetics of mycobacterial infectious diseases. He is also Head Laboratory of the Dept. of Infectious Diseases and Head of the Group Immunology and Immunogenetics of Bacterial Infectious Diseases.

Brief research profile and mission statement

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

Tuberculosis research is a major theme in my research programs. Its TB research is fundamental, preclinical, translational as well as clinical in nature and includes partly humanized animal models of TB. Research efforts aim to develop better vaccines, as well as  diagnostic, immunologic, transcriptomic and metabolic “biomarker signatures”. This 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 (SA, Gambia, Gabon, Ethiopia, Indonesia, Brazil, China, etc.).  The group has a strong international reputation, and an extensive portfolio of external competitive projects. 

Some contributions

We have established an internationally esteemed research programme in the field of human immunology, cell biology and immunogenetics of mycobacterial infectious diseases.  Amongst some of our scientific contributions, we discovered the first specific antigens for mycobacterium reactive T-cells in humans, were involved in identifying the first Thelper-1 cells in humans, discovered a new human immunodeficiency due to genetic mutations in the receptor for interleukin-12, cloned the first monoclonal T-regulatory cells in humans, have been involved in many human genetic studies that identified, with excellent collaborators, multiple new genetic variants impacting on risk of tuberculosis and leprosy, together with prof. Jacques Neefjes identified a new human PKB/Akt1 controlled signaling pathway that is manipulated by Salmonella and Mtb to inhibit phagosomal-lysosomal fusion, identified receptor tyrosine kinasese to be new targets for host directed therapy in TB (Nat Comm, in press), and executed several clinical phase I/IIa trials testing safety and long-term immunogenicity of new TB subunit vaccines.  Our scientific mission is to dissect immunological and host-genetic mechanisms of protective and pathologic immunity to mycobacterial infections and related infectious diseases, in order to design more effective intervention strategies.  One focus is on the role of T cell subsets (T-helper, T-regulatory), macrophage subsets, intracellular signaling networks, cellular function and systems biology.  A second, more translation-oriented focus is on Mtb antigen discovery, TB vaccine design, novel TB diagnostic test development and TB biomarker discovery. 

I have been a member of the advisory board of a LUMC Biotech spin off company, ISA Pharmaceuticals.

Training of postdocs and PhD students

I have had the privilege of working with many excellent students and researchers in the lab over the years.  I have supervised 18 PhD students theses, have been and am involved as adviser in others.  I have supervised >20 postdoctoral fellows. 

Training and Degrees

• 1982  MD degree, Leiden University Medical Center (LUMC)
• 1986 PhD (cum laude), Leiden University (“HLA class II immune response genes in leprosy”

Academic appointments

• 1982-1986 PhD training and Clinical Blood Bank Consultant in Transfusion Medicine at LUMC
• 1986-1988 Senior Scientist at Armauer Hansen Research Institute, Addis Ababa, Ethiopia
• 1989-1993 Honorary Huygens Fellowship Award (Netherlands Organization for Scientific Research); based at LUMC
• 1991-1993 Visiting Professor at the Cell Biology and Metabolism Branch, NICHD, NIH, Bethesda, MD
• 1994 Assistant Professor at LUMC
• 1998 Associate Professor at LUMC
• 2001 Full Professor at LUMC and Leiden University (Dept. Infectious Diseases, Center)
• 2008 Visiting Professor at Stanford University (Dept Microbiology and Immunology, prof. Gary Schoolnik, Stanford University School of Medicine), Palo Alto, CA.

Academic Honors and Indicators of Esteem

General

• Several personal awards (Eijkman Medal, Swierenga Medal, American Acad. Microbiology distinction).
• Regular presentations as invited speaker on international, national congresses and public meetings.
• Member of many large projects’ Steering Committees
• Participation in advisory boards (monitoring- and evaluation committees)
• Member Senior Management Team TBVI (since 2015)

Specific

• 1989-1993 C. and C. Huygens Fellowship Award (Netherlands Organization for Scientific Research)
• 1996 C.J. Kok Award, Leiden University
• 1999-2005 Member various Review Panels of Deutsche Forschungsgemeinschaft on Vaccine Projects
• 2002-2008 Member of the NWO-VENI Research Committee (Netherlands Organisation for Scientific Research, Innovation Research program) for promising young scientists
• 2003-2013 Member of the "Gezondheidsraad" (Netherlands Government Council of Health), Section Infection and Immunity.
• 2003-present Member Scientific Advisory Panel TB Vaccines for the World 2004, 2006, 2008, 2012
• 2003-2006 Member Editorial Board Infection and Immunity
• 2004-present Member Editorial Board Current Immunology Reviews.
• 2004 Guest Editor Current Opin. Immunol. (with Michael Bevan) on "Host Pathogen interactions".
• 2005 Guest Editor Microb. Infect. Issue on "Host Genetics and Mycobacterial Infectious Diseases"
• 2006-2010 Member of the "Gezondheidsraad" (Netherlands Government Council of Health), Expert Advisory Committee on BCG Vaccination.
• 2006-present Member Review Panel Deutsche Forschungsgemeinschaft on “Initiative for new German Centers of Excellence and Master Schools”.
• 2007-present Member Editorial Board The Open Microbiology Journal
• 2007-present Member of Stop TB Core Working Group on New Vaccines- Task Force Laboratory Assays
• 2007-2010 Member Working Group on Use of Infected Target Cells for Assessing Protective Efficacy of new TB Vaccines.  Organiser of the International Workshop/Symposium on Discovery of New Mtb Antigens Expressed on Infected Cells (WHO, Geneva).
• 2008 Co-founding Member Tuberculosis Vaccine Initiative (see www.tbvi.eu)
• 2008, 2012 Advisor to the Gates Foundation on TB Biomarkers
• 2008-2009 Member of the European Academies Science Advisory Council (EASAC)(on behalf of the Dutch Government), Working Group on Drug-resistant Tuberculosis
• 2008 Adviser to WHO and EC at "TDR-EC joint expert consultation meeting to evaluate the role of bio-surrogate markers in the management of HIV-infected and -uninfected TB patients
• 2010 Eurolife Distinguished Faculty Speaker, Trinity College, Dublin, Ireland
• 2011-present Member of the “Decade for Vaccines” R&D Working Group
• 2012-present Member Editorial Board American Journal of Clinical and Experimental Immunology
• 2013 Eijkman medal awarded
• 2012 Member of the Biomarker Core Working group, Aeras Foundation, Rockville USA
• 2014 Elected Fellow American Academy of Microbiology (an honorific society of microbiologists who have distinguished themselves in research, education, clinical science, or administration).
• 2014 J Swierenga medal awarded
• 2011-2018 Elected member of ERC starting grant evaluation panel LS6 (Infection and Immunity)
• 2018 Adviser to WHO at TDR consultation on TB Vaccines development.  

Publications