2021 Fiscal Year Final Research Report
Development of Therapeutic Modality for Cancers by Reviving Ancient Signal Pathways That Human Has Lost During Evolution
Project/Area Number |
20K20464
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Project/Area Number (Other) |
19H05554 (2019)
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Research Category |
Grant-in-Aid for Challenging Research (Pioneering)
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Allocation Type | Multi-year Fund (2020) Single-year Grants (2019) |
Review Section |
Medium-sized Section 49:Pathology, infection/immunology, and related fields
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Research Institution | The University of Tokyo |
Principal Investigator |
Katoh Hiroto 東京大学, 大学院医学系研究科(医学部), 准教授 (60446549)
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Project Period (FY) |
2019-06-28 – 2022-03-31
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Keywords | 機能ゲノミクス・スクリーニング / 微生物ゲノム / がん治療 / 次世代シーケンス / 合成生物学 |
Outline of Final Research Achievements |
In this research project, I established lentivirus libraries consisting of global microbial ORFs in a format that is able to be overexpressed in mammalian cells. Then, I established an experimental protocol by which single microbial gene is integrated into one human cancer cell. The heterogenous human cancer cell populations after lentivirus infection were implanted into mice; then, resultant in vivo tumors were subjected to DNA purification and NGS analysis. By counting population sizes of the microbial gene clones in the tumors of heterogenous human cancer cells, candidate microbial genes that could inhibit cell growth or induce cell death in human cancer cells were explored. I succeeded in identifying multiple microbial genes by this screening. Taken together, I developed a highly original method of functional genomics screening which successfully covers an extremely wide screening space.
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Free Research Field |
ゲノム科学を基盤としたがん研究
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Academic Significance and Societal Importance of the Research Achievements |
がん細胞はその生存・増殖のために特異的な遺伝子変異やシグナル異常に依存していることが多く、そのような特異的な変異遺伝子や異常シグナルの阻害を狙った分子標的治療の開発が活発に進められている。ところが、がん細胞にみられる遺伝子異常やシグナル伝達異常についての多くの知見が得られているにもかかわらず、有効な分子標的治療薬の開発は困難なままである。がんに対する有効な分子標的治療薬の開発は社会的に求められており、新しいタイプの分子標的候補の同定は重要な研究課題といえる。本研究は、新規がん治療標的候補の探索を目的として、新しいがん分子標的探索スクリーニング法の開発を計画したものである。
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