Integrative understanding of gastrointestinal disease phenotypes using organoid library

2021 Fiscal Year Final Research Report

• Project/Area Number: 17H06176
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: Keio University
• Principal Investigator: SATO Toshiro 慶應義塾大学, 医学部(信濃町), 教授 (70365245)
• Project Period (FY): 2017-05-31 – 2022-03-31
• Keywords: 大腸がん / 膵がん / 胃がん / オルガノイド / Wntシグナル / 幹細胞

Outline of Final Research Achievements

Digestive tissues are subject to a variety of diseases, including tumors. However, due to the lack of analytical platforms, our understanding of the pathogenesis of human gastrointestinal tissues has lagged behind. We have been working to understand the pathogenesis of diseases and to develop new therapies using organoid technology, which enables in vitro cultivation of tissues with gastrointestinal diseases. We have established organoids from various gastrointestinal disease tissues, including ulcerative colitis, gastric cancer, colorectal cancer, pancreatic cancer, and endocrine cell carcinoma, and constructed a biobank such that researchers can utilize them. In addition, molecular profiling of disease organoids elucidated the biological mechanism underlying the diseases. We also employed genome editing technology and animal models to gain a better understanding of new gastrointestinal diseases.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

消化器疾患は、近年増加の一途にある潰瘍性大腸炎や本邦のがん死亡原因の大部分を占めており、病態の理解と治療法開発が急務である。本研究成果は、ヒト疾患組織を直接的に研究するアプローチをとっており、従来の動物モデル研究とは一線を画す研究を展開した。 研究代表者らは、疾患組織の生物学的な形質に着目し、その遺伝子変異や遺伝子発現ネットワークレベルでの理解を深めた。研究成果はNature, Cellなどの一流誌に掲載され、国内外での高い評価を受けた。さらに、培養技術や治療方法などの知財を取得し、今後の本邦の研究開発に資するという観点から社会的なインパクトも大きい。