| Project/Area Number |
16K09872
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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 |
Hematology
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| Research Institution | International University of Health and Welfare (2017-2018)
Osaka University (2016) |
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Principal Investigator |
ORITANI KENJI 国際医療福祉大学, 医学部, 教授 (70324762)
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| Co-Investigator(Kenkyū-buntansha) |
前田 哲生 大阪大学, 医学系研究科, 助教 (00403064)
金倉 譲 大阪大学, 医学系研究科, 教授 (20177489)
一井 倫子 大阪大学, 医学系研究科, 寄附講座助教 (30633010)
戸田 淳 大阪大学, 医学部附属病院, 医員 (90770834)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | STAP / アダプター蛋白 / 免疫応答 / 慢性骨髄性白血病 / 移植片対宿主病 / 造血幹細胞移植 / 免疫反応 / 腫瘍化 / シグナル伝達 / 炎症反応 / GVHD / T細胞受容体 / 遺伝子 / 蛋白質 / 免疫学 / 内科 |
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| Outline of Final Research Achievements |
We analyzed functional mechanisms of adaptor protein STAP and possible involvement in disease development.
We newly found positive regulation of T-cell receptor signals by STAP through its binding to LCK and CD3-ITAM. We also showed that STAP is involved in maintenance of chronic myelocytic leukemia stem cells. We established GVHD experimental model using STAP-transgenic mouse, and found that over-expression of STAP in T-lymphocytes highly enhanced clinical symptoms of graft-versus-host disease.
Therefore, we could show potential of clinical utilities of STAP-inhibitors in the fields of the elimination of chronic myelocytic leukemia stem cells and the prevention and treatment of graft-versus-host disease after allogenic hematopoietic stem cell transplantation.
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| Academic Significance and Societal Importance of the Research Achievements |
STAPアダプター蛋白の免疫応答への関与を明らかにするとともに、慢性骨髄性白血病や移植片宿主病の病因・病態へのSTAPの関与を明らかにした。このことは、自己免疫疾患などの難治性疾患や一部の腫瘍において、STAP人為的操作による治療の可能性を示唆するものである。STAP阻害剤開発後の治療対象疾患の縛り込みに成功した。
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