Dr. Emiko Mizoguchi's Research

Emiko Mizoguchi, M.D. Ph.D.
Assistant Professor of Medicine,
Harvard Medical School

Address:

Massachusetts General Hospital
Jackson 702
55 Fruit Street
Boston, MA 02114

Phone: (617) 724-2172
E-Mail: emizoguchi@partners.org

Major Research Interests:

Lab Members:

Research Projects:

My research interest is to investigate the basic cellular and molecular mechanisms involved in the functional modulation of colonic epithelial cells (CEC) during the development of inflammatory bowel disease (IBD). The study includes identifying the key molecules which are regulating the CEC/microorganism interaction, CEC/lamina proprial cell interaction, and intestinal epithelial cell barrier function.

Our research group has utilized experimental models of IBD to understand the mechanisms in the pathogenesis of chronic colitis, which include T cell receptor alpha chain (TCRa) knockout (KO) mice, CD45RBhi cell transfer mice, IL-10 KO mice, IL-2 KO mice, and dextran sulfate sodium induced colitis models (Inflammatory Bowel Disease, 2003, 9:246-259).

My laboratory currently focuses on studying the functional role of tumor necrosis factor receptor type-I (TNFR1) and type-II (TNFR2) on CEC in colitis. TNFR1 protein is constitutively expressed on the wide variety of cell types, but TNFR2 only expressed on the highly activated cells. It has been well characterized that the dual signaling pathways (cell death and cell proliferation) are stimulated by TNFR1 and TNFR2 in T cells. Recently, we have identified that TNFR2 expression is induced on the surface of CEC under inflammatory conditions seen in human IBD as well as several murine models of colitis (Gastroenterology, 2002, 122:134-144). Recently, we identified that TNFR1-signaling cascade in colonic myeloid lineage cells contributes to the suppression of acute damage associated mortality by controlling CEC homeostasis (Gastroenterol, 2008, 134:470-480). Although it is clear that TNFa/TNFRs interactions in T cells play a crucial pathogenic role in colitis, the effects of TNFa/TNFRs interactions on CEC function have not been fully defined yet. Our studies will help clarify the distinct roles of TNFRs in the pathogenesis of colitis and providing new therapeutic approach based on the modification of TNFa/TNFRs interactions in human IBD.

Recently, by employing DNA microarray analysis (Gastroenterology, 2003, 125:148-161) using dextran sulfate sodium colitis model, we unexpectedly discovered significantly upregulated gene expression of Chitinase 3-like-1 (CHI3L1) molecule in colonic mucosa (mainly expressed in CEC and macrophages). The subsequent studies defined that CHI3L1 upregulation is a common feature of intestinal inflammation as indicated by the upregulation of this molecule in acute and chronic colitis models as well as human IBD. The CHI3L1 was upregulated after pro-inflammatory cytokines stimulation and enhanced the adhesion and internalization of intracellular bacteria in epithelial cells. Most importantly, in vivo neutralization of CHI3L1 activity significantly suppressed the development of acute colitis by dramatically decreasing the bacterial invasion into intestinal mucosa. Our present study provides a novel insight into the physiological role of mammalian chitinases in host/microbial interactions (Gastroenterology, 2006, Immunologic Research, 2007, 37:47-60, Lab Invest, 2008, in press). We will expand the study of CHI3L1 and the other members of mammalian chitinases (e.g., acidic mammalian chitinase and chitotriosidase) to acute and chronic colitis in animal models as well as human IBD. Chitinase-like molecules are most likely a potential therapeutic target that can be manipulated to control IBD and other forms of inflammatory disorders.

Former Lab Members:

Recent Publications:

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