| Project/Area Number |
24689036
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Partial Multi-year Fund |
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| Research Field |
Gastroenterology
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| Research Institution | Keio University |
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Principal Investigator |
SATO Toshiro 慶應義塾大学, 医学部, 特任准教授 (70365245)
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| Research Collaborator |
MATANO Mami 慶應義塾大学, 医学部, 研究員 (20439889)
TAKANO Ai 慶應義塾大学, 医学部, 研究員 (50647584)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥25,740,000 (Direct Cost: ¥19,800,000、Indirect Cost: ¥5,940,000)
Fiscal Year 2013: ¥12,090,000 (Direct Cost: ¥9,300,000、Indirect Cost: ¥2,790,000)
Fiscal Year 2012: ¥13,650,000 (Direct Cost: ¥10,500,000、Indirect Cost: ¥3,150,000)
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| Keywords | 大腸がん / 幹細胞 / 腸管上皮幹細胞 / WNT / LGR5 |
|---|
| Research Abstract |
We have established intestinal organoids from human intestinal epithelium and applied genome engineering system to organoids. With this approach, we introduced multiple driver mutations into human intestinal organoids to elucidate the mechanism of colorectal carcinogenesis. Furthermore, we knocked-in reporter to LGR5 locus of intestinal organoids using genome editing. Owing to the genetic silencing of Lgr5 promoter, we are attempting to employ other stem cell genetic markers. We also established xenotransplantation system with engineered organoids or colorectal cancer organoids. The organoids were readily engrafted and form tumor recapitulating clinical colorectal cancer. Our results suggest that engineered organoid system provide new insights into the understanding of human colorectal cancer. The platform will be useful not only to elucidate cell biological mechanism of colorectal cancer stem cells but also to apply genetic mutation based drug discovery and personalized medicine.
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