2021 Fiscal Year Research-status Report
tRNA epitranscriptome in regulating glioma therapeutic resistance
| Project/Area Number |
20KK0338
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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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| Keywords | Glioma / tRNA / CRISPR / Chemotherapy / Epigenetics |
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| Outline of Annual Research Achievements |
Joined the Dedon Laboratory in MIT starting February 2022 as intended in the research plan. Currently focusing on techniques related to tRNA modification analysis and how to apply these techniques to study glioma in basic and clinical research. In this project, I identified 2 tRNA methylation modifications that play important role in glioma pathogenesis, m1A and m7G. Either modification impacted glioma cell proliferation, protein synthesis, and response to ferroptosis and chemotherapy. The enzyme responsible for m1A modifications in glioma is currently being studied using animal models of glioma, cell model systems, and in silico screening for drug discovery. The enzyme responsible for m7G modifications is currently being studied using cell culture systems and animal models of glioma.
In a separate effort, I Identified epitranscriptional factors that regulate ferroptosis in glioma. The article is currently under review.
I also conducted genome wide CRISPR screening to identify regulators of ferroptosis in glioma cells. The screen led to the identifications of translational processes such as Ribosome collision and tRNA aminoacylation as important regulators of ferroptosis in glioma. These processes are currently under research.
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| Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
Identified various tRNA modifying enzymes that regulate tRNA pathology and response to therapy. Currently these enzymes are under study.
Submitted one article based on the work conducted in this R&D project.
Succeeded in using CRISPR screening to identify factors related to glioma ferroptosis sensitivity and identified various tRNA related processes.
Joined MIT as a visiting professor as planned in the research plan of this project.
Identified an enzyme target for therapy to be used in glioma therapy and currently planning to start identifying small molecule inhibitors for this enzyme.
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| Strategy for Future Research Activity |
Continuing the analysis of tRNA modifying enzymes and their role in glioma pathophysiology and ferroptosis resistance.
Plans for the analysis of tRNA expression and modifications using samples from glioma patients to supplement the findings of the basic research conducted.
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