tRNA epitranscriptome in regulating glioma therapeutic resistance

2022 Fiscal Year Annual Research Report

• Project/Area Number: 20KK0338
• Research Institution: Tohoku University
• Principal Investigator: Rashad Sherif 東北大学, 医学系研究科, 助教 (00824088)
• Project Period (FY): 2020 – 2022
• Keywords: tRNA modifications / Glioma / Ferroptosis / mRNA translation / Codon usage / Bioinformatics / Mass spectrometry

Outline of Annual Research Achievements

During my stay with Prof Dedon, I was able to learn high throughput LC-MS method for the analysis of tRNA and RNA modifications. Using this method, I studied the impact of ferroptosis on glioma cells as well as the effect that some tRNA modifying enzymes have on glioma. I was able to identify various therapeutic targets. I also used this system to generate data on oxidative stress response, neural differentiation, and neurodegeneration. In addition, I learned methods for analysis of codon usage and bias in sequencing and proteomics datasets, which can be used to optimize gene constructs in genetic therapy approaches such as mRNA vaccines. Using this method I published a paper linking codon bias, ferroptosis, and tRNA modifications in glioma (Rashad et al, Neuroscience, 2022). Currently, there are 5 papers in preparation being written by myself or my students that are using data generated during my work at the Dedon lab.

Research Products

• [Int'l Joint Research] Massachusetts Institute of Technology,(米国) (2022)
  • Year and Date: 2022-02-15 – 2023-02-14
  • Country Name: U.S.A.
  • Counterpart Institution: Massachusetts Institute of Technology,
  • Co-investigator Overseas: Peter C Dedon
  • Department: Biological Engineering
  • Job Title: Professor
• [Journal Article] Accumulation of m6A exhibits stronger correlation with MAPT than beta-amyloid pathology in an APP NL-GF/MAPT P301S mouse model of Alzheimer's disease (2023)
  • Author(s): Lulu Jiang, Rebecca Roberts, Melissa Wong, Lushuang Zhang, Chelsea Joy Webber, Alper Kilci, Matthew Jenkins, Sherif Rashad, Jingjing Sun, Peter Dedon, Sarah Anne Daley, Weiming Xia, Alejandro Rondon Ortiz, Luke Dorrian, Takaomi C Sado, Takashi Saido, Benjamin Wolozin
  • Journal Title: Biorxiv preprint Volume: - Pages: 111-112
  • DOI: 10.1101/2023.03.28.534515
  • Int'l Joint Research
• [Journal Article] Codon Usage and mRNA Stability are Translational Determinants of Cellular Response to Canonical Ferroptosis Inducers (2022)
  • Author(s): Sherif Rashad, Shane R Byrne, Daisuke Saigusa, Jingdong Xiang, Yuan Zhou, Liyin Zhang, Thomas J Begley, Teiji Tominaga, Kuniyasu Niizuma
  • Journal Title: Neuroscience Volume: 501 Pages: 103-130
  • DOI: 10.1016/j.neuroscience.2022.08.009
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Neuronal sensitivity to oxidative stress is epitranscriptionally programmed (2022)
  • Author(s): Sherif Rashad, Yuan Zhou, Kuniyasu Niizuma
  • Organizer: The Society for Redox Biology and Medicine's 29th Annual Conference (SfRBM 2022)
  • Int'l Joint Research
• [Presentation] Codon usage and mRNA stability are translational determinants of cellular response to canonical ferroptosis inducers (2022)
  • Author(s): Sherif Rashad
  • Organizer: The Society for Redox Biology and Medicine's 29th Annual Conference (SfRBM 2022)
  • Int'l Joint Research