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Laboratory of Host Defenses

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Warren Strober, M.D.

Photo of Warren Strober, M.D.

Chief, Mucosal Immunity Section, LHD

Major Areas of Research

  • Basic studies of mucosal immunity, mucosal inflammation, and inflammatory bowel disease such as ulcerative colitis and Crohn’s disease
  • Studies of immunodeficiency such as common variable immunodeficiency and hyper-IgM syndrome
  • Studies of the immunobiology of inflammatory cytokines
  • Studies of innate immunity in the mucosal immune system
 

Program Description

The Mucosal Immunity Section (MIS) conducts a broad spectrum of studies on the immune system of mucosal surfaces. Over the years, the section has gained prominence for studies of basic mechanisms of the mucosal immune response and diseases resulting from disorders of these mechanisms.

In one major area of study, section scientists have made extensive use of experimental models to understand the complex cellular and molecular events governing mucosal inflammation. On the one hand this has led to new insights into the effector and regulatory mechanisms at play during gastrointestinal inflammation and, on the other hand, to the development of new approaches to the treatment of human counterpart diseases: Crohn’s disease and ulcerative colitis. In one such approach, the treatment of Th1/Th17-based mucosal inflammation with anti-IL-12p40 has shown promise as a treatment of Crohn’s disease in a human clinical trial conducted by members of the section. In another such approach, the treatment of NKT cell/IL-13 –based mucosal inflammation with anti-IL-13 agents has resulted in clinical studies of therapies for ulcerative colitis using agents that neutralize IL-13.

In related studies focusing on the molecular basis of mucosal inflammation, section scientists have conducted ground-breaking studies of the mechanism by which CARD15 (NOD2) polymorphisms cause Crohn’s disease. They have shown that NOD2 normally down-regulates innate immune responses via TLR signaling and that CARD15 polymorphisms in Crohn’s disease compromise this regulation and thus lead to excessive production of Th1/Th17 cytokine production.

In other basic studies of the mechanisms of mucosal inflammation, section scientists have elucidated the effector mechanisms underlying regulatory T cell activity and have conducted extensive studies of the molecular regulation of cytokine synthesis.

Finally, scientists in the section couple their interests in diseases related to mucosal immunity with interests in immunodeficiency diseases. This is evident in long-standing studies of common variable immunodeficiency, IgA deficiency, and other immunodeficiency states.

MIS has long been a breeding ground for highly regarded immunologists, and this teaching tradition is alive and well in the section. Fellows are given well-defined and independent projects and are encouraged to be creative within their assigned areas (or outside of their assigned areas, at times).

Biography

Dr. Strober obtained his medical degree from the University of Rochester and completed an internship and residency at Strong Memorial Hospital. He has served as NIAID deputy scientific director and as the interim scientific director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Dr. Strober is a leader in the study of mucosal antibody responses, oral tolerance, and gastroenterological diseases caused by immunologic abnormalities. His discoveries concerning the mucosal immune system have formed the basis of our knowledge of IgA B cell development and the mechanisms of mucosal inflammation.

Dr. Strober is the recipient of numerous awards, including the Distinguished Achievement Award of the American Gastroenterological Association and the PHS Distinguished Achievement Medal. In addition, he has been awarded an Honorary Doctorate from the Humboldt University, Berlin. Dr Strober has provided leadership to the scientific community as chair of the American Board of Allergy and Immunology and as president of the Society for Mucosal Immunity.

Research Group

Other permanent members of the Mucosal Immunity Section include Dr. Ivan Fuss and Dr. Atsushi Kitani. Dr. Fuss is a staff clinician in the section and has a distinguished research record in the study of murine models of inflammation; in addition, Dr. Fuss has been a leader in the conduct of clinical trials of new agents for the treatment of inflammatory bowel disease. Dr. Kitani is a staff scientist in the section and has played a prominent role in the conduct of studies focusing on the molecular mechanisms underlying mucosal inflammation. He has vast experience in the use of molecular constructs both as research tools and as therapeutic modalities.

Selected Publications

Fuss IJ, Friend J, Yang Z, He JP, Hooda L, Boyer J, Xi L, Raffeld M, Kleiner DE, Heller T, Strober W. Nodular regenerative hyperplasia in common variable immunodeficiency. J Clin Immunol. 2013 May;33(4):748-58.

Strober W. Adherent-invasive E. coli in Crohn disease: bacterial "agent provocateur". J Clin Invest. 2011 Mar;121(3):841-4.

Watanabe T, Asano N, Kitani A, Fuss IJ, Chiba T, Strober W. NOD1-Mediated Mucosal Host Defense against Helicobacter pylori. Int J Inflam. 2010 Jul 15;2010:476482.

Strober W. The LTi cell, an immunologic chameleon. Immunity. 2010 Nov 24;33(5):650-2.

Strober W. Inside the microbial and immune labyrinth: Gut microbes: friends or fiends? Nat Med. 2010 Nov;16(11):1195-7.

Xu L, Kitani A, Stuelten C, McGrady G, Fuss I, Strober W. Positive and negative transcriptional regulation of the Foxp3 gene is mediated by access and binding of the Smad3 protein to enhancer I. Immunity. 2010 Sep 24;33(3):313-25.

Visit PubMed for a complete publication listing.

Last Updated June 12, 2014