Medical Sciences Group/Intra-University Cooperative LaboratoriesHirata Laboratory
(Division of Advanced Genome Medicine, IMS)

Our laboratory conducts comprehensive research on the diseases of digestive tract from the genome (human, mouse, bacteria, and virus) to the organ, or the individual. One of the main subjects of research are inflammatory diseases caused by pathogens, autoimmunity, and genetic abnormalities, such as gastritis, hepatitis, and colitis. Another subject is malignant tumors, such as gastric cancer, colon cancer, liver cancer, and pancreatic cancer. Based on clinical knowledge, we promote translational researches which aimed at elucidating the pathological mechanisms at the genetic and molecular level and developing new treatment methods using mouse models.

gastroenterology, inflammation, cancer, immunity, animal model
Development of mouse cancer model and new therapeutic strategy
  • Development and analysis of genetic engineered cancer model

Analysis of pathogenesis of inflammatory diseases of digestive system

There are various intractable and chronic inflammatory diseases in digestive systems, such as gastritis, colitis, cholangitis, etc. Some of them are caused by pathogens, others by autoimmune abnormalities, and the mechanisms of their onset and progression are largely unknown. Using mouse models, we aim to visualize the complex interactions between epithelial cells, immune cells, pathogens, and other organic structures that are involved in the pathogenesis of these inflammatory diseases. We will also try to develop new treatments base on the mechanisms elucidated by animal models.

  • Analysis of cellular interactions in colitis

  • Development of new gastrointestinal allergy model

  • 1. Hayata Y, Nakagawa H, Kurosaki S, Kawamura S, Matsushita Y, Hayakawa Y, Suzuki N, Hata M, Tsuboi M, Kinoshita H, Miyabayashi K, Mizutani H, Nakagomi R, Ikenoue T, Hirata Y, Arita J, Hasegawa K, Tateishi K, Koike K. Axin2+ Peribiliary Glands in the Periampullary Region Generate Biliary Epithelial Stem Cells That Give Rise to Ampullary Carcinoma. Gastroenterology. 2021 May;160(6):2133-2148.e6. doi: 10.1053/j.gastro.2021.01.028. Epub 2021 Jan 16. PMID: 33465373.
  • 2. Kinoshita H, Hayakawa Y, Konishi M, Hata M, Tsuboi M, Hayata Y, Hikiba Y, Ihara S, Nakagawa H, Ikenoue T, Ushiku T, Fukayama M, Hirata Y, Koike K. Three types of metaplasia model through Kras activation, Pten deletion, or Cdh1 deletion in the gastric epithelium. J Pathol. 2019 Jan;247(1):35-47. doi: 10.1002/path.5163. Epub 2018 Nov 27. PubMed PMID: 30168144.
  • 3. Ihara S, Hirata Y, Hikiba Y, Yamashita A, Tsuboi M, Hata M, Konishi M, Suzuki N, Sakitani K, Kinoshita H, Hayakawa Y, Nakagawa H, Ijichi H, Tateishi K, Koike K. Adhesive interactions between mononuclear phagocytes and intestinal epithelium perturb normal epithelial differentiation and serve as a therapeutic target in inflammatory bowel disease. J Crohns Colitis. 2018 Nov 9;12(10):1219-1231. doi:10.1093/ecco-jcc/jjy088. PubMed PMID: 29917067.
  • 4. Nakagawa H, Suzuki N, Hirata Y, Hikiba Y, Hayakawa Y, Kinoshita H, Ihara S, Uchino K, Nishikawa Y, Ijichi H, Otsuka M, Arita J, Sakamoto Y, Hasegawa K, Kokudo N, Tateishi K, Koike K. Biliary epithelial injury-induced regenerative response by IL-33 promotes cholangiocarcinogenesis from peribiliary glands. Proc Natl Acad Sci U S A. 2017 May;114(19):E3806-E3815. doi: 10.1073/pnas. 1619416114. [Epub ahead of print] PubMed PMID: 28439013.
  • 5. Ihara S, Hirata Y, Serizawa T, Suzuki N, Sakitani K, Kinoshita H, Hayakawa Y, Nakagawa H, Ijichi H, Tateishi K, Koike K. TGF-β Signaling in Dendritic Cells Governs Colonic Homeostasis by Controlling Epithelial Differentiation and the Luminal Microbiota. J Immunol. 2016 Jun 1;196(11):4603-13. doi: 10.4049/jimmunol.1502548. Epub 2016 Apr 22. PubMed PMID: 27183608.
  • 6. Hirata Y, Egea L, Dann S, Eckmann L, Kagnoff M. GM-CSF-facilitated dendritic cell recruitment and survival govern the intestinal mucosal response to a mouse enteric bacterial pathogen. Cell Host Microbe 2010;7:151-63.
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