Therapeutic strategy to target epithelial stem cell specific epigenetic regulation
Project/Area Number |
17K16332
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Dermatology
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Research Institution | Kanazawa University |
Principal Investigator |
hazawa masaharu 金沢大学, 新学術創成研究機構, 助教 (40622460)
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2019: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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Keywords | 核膜孔複合体 / エピジェネティクス / 腫瘍生物学 / 分子細胞生物学 / 扁平上皮癌 / 遺伝子発現 / 上皮分化 / 皮膚組織幹細胞 / 癌 / 遺伝子 / ゲノム / 細胞・組織 |
Outline of Final Research Achievements |
This study aims to unmask stem-cell specific epigenetics regulation by nuclear pore complex (NPC). I found that NPCs-mediated spatial-regulation of genomic DNA resulted in activation of oncogene-expression. Further, interacting mode between NPC and transcription environment was identified. These results gives annotation spatio-temporal information of transcription regulators and its target genes. Further study of NPC-mediated genomic structure and function will unmask how NPC regulates cell-fate determination mechanisms and cancer initiation-/progression.
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Academic Significance and Societal Importance of the Research Achievements |
遺伝子発現制御は細胞の形質決定に関わる機構である。これまでに幹細胞や癌細胞で中心的役割を担う転写制御因子とこれらの標的遺伝子の解明がなされてきたが、核内における構造・機能相関の解明は未だなされていかった。 本研究により、NPCが核内ゲノムの配置・機能制御に関与すること、さらにNPCとゲノムの相互作用機序の一部を解明できた。本研究により明らかにされた、NPC-ゲノム相互作用阻害により、人為的な遺伝子発現操作をできる可能性があり、再生医療や癌治療への応用が期待される。
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Report
(4 results)
Research Products
(17 results)
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[Journal Article] Co-activation of super-enhancer-driven CCAT1 by TP63 and SOX2 promotes squamous cancer progression.2018
Author(s)
Jiang Y, Jiang YY, Xie JJ, Mayakonda A, Hazawa M, Chen L, Xiao JF, Li CQ, Huang ML, Ding LW, Sun QY, Xu L, Kanojia D, Jeitany M, Deng JW, Liao LD, Soukiasian HJ, Berman BP, Hao JJ, Xu LY, Li EM, Wang MR, Bi XG, Lin DC, Koeffler HP.
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Journal Title
Nat Commun.
Volume: 9
Issue: 1
Pages: 3619-3619
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Rock-dependent phosphorylation of NUP62 regulates p63 nuclear transport and cell fate of squamous cell carcinoma.2018
Author(s)
Hazawa M, Lin D, Kobayashi A, Jiang YY, Dewi FRP, Mohamed MS, Hartono H, Nakada S, Meguro-Horike M, Horike S, Koeffler H and Wong RW
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Journal Title
EMBO Rep.
Volume: 19
Issue: 1
Pages: 73-88
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] High-Speed Atomic Force Microscopy Reveals Loss of Nuclear Pore Resilience as a Dying Code in Colorectal Cancer Cells.2017
Author(s)
Mohamed MS, Kobayashi A, Taoka A, Watanabe-Nakayama T, Kikuchi Y, Hazawa M, Minamoto T, Fukumori Y, Kodera N, Uchihashi T, Ando T, Wong RW
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Journal Title
ACS Nano.
Volume: 11(6)
Issue: 6
Pages: 5567-5578
DOI
Related Report
Peer Reviewed / Open Access
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