Atsushi Mizoguchi, MD, PhD
Associate Immunologist, non-clinical
Massachusetts General Hospital
Associate Professor of Pathology
Harvard Medical School
Inflammatory bowel disease (IBD) is a group of chronic, relapsing and remitting inflammatory conditions that affect individuals throughout the life. My laboratory has explored the immune mechanism involved in the development/progression of IBD by using genetically engineered mouse models, and is currently developing a novel rationale for applying cell-specific and tissue-specific therapy to diverse disease conditions in the digestive tract ranging from IBD to cancer. In addition to research activity, I have served as Editorial Board Members in Gastroenterology, Journal of Immunology, and Journal of Gastroenterology.
IL-22: An IL-10 cytokine family, IL-22 serves as a specific activator of innate immune responses through signal transducer and activator of transcriptions (STAT) 3. My laboratory recently identified the therapeutic potential of IL-22 in murine models of IBD (J Clin Invest 2008,118:534). The importance of this finding from mice is highlighted by more recent human genetic studies identifying IL-22 and its receptor as IBD susceptibility genes. My laboratory is currently studying how IL-22 suppresses colitis and if intestine-specific IL-22 gene therapy can be used for treatment of IBD particularly ulcerative colitis.
Tissue-specific and cell-specific therapy: Over one million patients each year are newly diagnosed with digestive diseases, such as IBD and colorectal cancer. Digestive tracts are relatively easily accessible by endoscopy for diagnosis and therapy. In collaboration with Dr. Andy Yun, we are currently developing an endoscopic optical image-guided immobile-cell delivery system that can non-invasively make an in vivo diagnosis of digestive diseases at the microscopic resolution (Nat Method 2010,7:303) and can simultaneously perform the tissue-specific and cell-specific biological therapy through immobile cell- and mesenchimal stem cell-mediated gene delivery systems that are designed to specifically targets either, but not both, of adaptive or innate immune cells.
Breg: My laboratory, in collaboration with Dr. Atul Bhan, previously identified a regulatory B cell subset we have termed Breg, which produces large amounts of IL-10 and improves ongoing intestinal inflammation (Immunity 2002,16:219). The last three years have seen enormous progress in this area. Breg has now been confirmed to exist in diverse inflammatory conditions ranging from IBD to GVHD. My laboratory has recently expanded our initial observations to the discovery of an alternative pathway of B cell maturation in the intestine that gives rise to a tissue-specific B cell subset that we believe represents a precursor of Breg (J Exp Med 2008,205:1357). We are currently studying how these unique intestinal B cells differentiate into Breg and whether the cell-based therapy utilizing Breg precursors can be applied to IBD.
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