| Project/Area Number |
20KK0338
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| Research Category |
Fund for the Promotion of Joint International Research (Fostering Joint International Research (A))
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 50010:Tumor biology-related
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| Research Institution | Tohoku University |
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Principal Investigator |
RASHAD Sherif 東北大学, 医学系研究科, 助教 (00824088)
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| Project Period (FY) |
2020 – 2022
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥14,040,000 (Direct Cost: ¥10,800,000、Indirect Cost: ¥3,240,000)
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| Keywords | tRNA modifications / Glioma / Ferroptosis / mRNA translation / Codon usage / LC-MS / Bioinformatics / Mass spectrometry / tRNA / CRISPR / Chemotherapy / Epigenetics |
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| Outline of Research at the Start |
Studying Glioma epitranscriptome is a novel field of research. Here, I will study the dynamic tRNA epitranscriptome involved in Glioma chemotherapeutic responses to evaluate tRNA dynamics that influence this process and to develop future therapies for Glioma. Glioma cell lines will be exposed to various chemotherapeutic agents and studied for changes in tRNA levels and modifications using mass spectrometry and sequencing. Moreover, CRISPR screens will be used to identify potential targets for therapy that will be explored via genetic approaches.
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| Outline of Final Research Achievements |
During my overseas stay, I was able to learn methods for tRNA modifications analysis using a newly designed LC-MS-based high throughput method. Using this method, I analyzed tRNA modifications in a number of systems we used to study tRNA modifying enzymes. Using CRISPR KO, the impact of tRNA modifications was elucidated in cancer cells, and their impact on mRNA translation was further characterized via Ribosome profiling. In addition, I improved my bioinformatics skills via learning methods to study codon usage and bias and correlate these changes with distinct tRNA modifications signatures. I was able to use these new skills to study the translational impact of ferroptosis and tRNA modifying enzyme ALKBH1 in glioma cells (Rashad et al, Neuroscience, 2022)
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| Academic Significance and Societal Importance of the Research Achievements |
This work will open the doors for discovery of novel targets for cancer therapy that center on mRNA translation control. The first targets have been identified and currently under further studies. Using this system of analysis, novel biomarkers for various diseases can also be elucidated.
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