Development of novel therapeutic drugs targeting the mechanism of differentiation abnormality for tuberous sclerosis complex
| Project/Area Number |
26460398
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Juntendo University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
小池 正人 順天堂大学, 医学(系)研究科(研究院), 教授 (80347210)
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| Co-Investigator(Renkei-kenkyūsha) |
TADA Norihiro 順天堂大学, 医学研究科, 准教授 (50338315)
SUNAHORI Takehiko 順天堂大学, 医学部, 助教 (00407115)
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| Research Collaborator |
NISHIKAWA Keiko 順天堂大学, 医学研究科
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| Project Period (FY) |
2014-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 結節性硬化症 / モデル動物 / ES細胞 / 細胞分化 / Tsc2遺伝子 / 腫瘍 / mTORC1 / ラパマイシン / 胚性幹細胞 |
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| Outline of Final Research Achievements |
To develop novel therapeutic target molecules for tuberous sclerosis complex (TSC), a hereditary intractable disease, we focused on the abnormal differentiation caused by deficiency of TSC gene (TSC1、TSC2). As a new cellular differentiation model, we established ES cell lines from the Eker rat (Tsc2 mutant). We confirmed that Tsc2-deficient (homozygous mutant) ES cells had an ability to differentiate into various cells from three different germ layers. However, we found that Tsc2-deficient ES cells developed abnormal tissue structures in teratoma formation experiments. We also identified differential gene expression between Tsc2-deficient- and wild-type ES cells. As a candidate for the molecular basis of aberrant differentiation and gene expression in Tsc2-deficient ES cells, we identified difference in epigenetic modification between Tsc2-deficient- and wild-type ES cells. These will be clues to find new target molecules for TSC therapy.
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Report
(5 results)
Research Products
(10 results)
