Annual Report 2022
Division of Cancer RNA Research
Akihide Yoshimi, Asuka Kawachi, Marimu Sakumoto, Takahiro Nishino, Kazuki Nishimura, Atsuhito Nakayama, Guzhanuer Ailiken, Michiko Kurikawa, Hirofumi Yamauchi, Atsuro Oishi, Mayumi Hanzawa, Natsuko Shinohara, Ayano Go, Kota Otsuki
Introduction
In September 2022, we were promoted from the Cancer RNA Research Unit to the Division of Cancer RNA Research. In this new role, we have been advancing research on the mechanisms of cancer through abnormal RNA splicing, focusing on nucleic acid therapeutics-based drug development, drug discovery rooted in orphan receptors, and biomarker exploration across cancers through multi-omics approaches. In addition, we have initiated an ancillary study related to the "Phase 2 physician-initiated trial of EZH2 inhibitor (E7438) for patients with epithelioid sarcoma at four national facilities." Research projects led by Akihide Yoshimi have earned recognition through various grants and awards including the AMED Drug Discovery Foundation Promotion Research Project, AMED Next-Generation Cancer Medical Acceleration Research Project, AMED Bridging Research Seed A and Adjustment Funds, JST Emergent Research Support Project, and the American Society of Hematology (ASH) Global Research Award. Each of these awards has allowed us to commence research in their respective areas.
The Team and What We Do
Our lab members include one staff member, five graduate students, one student from the main hospital at the NCC, one external research staff, three technicians, one trainee and one office administrator. Our team aims to understand and target aberrant RNA splicing in cancers.
Research Activities
Through a multi-omics analysis of a bladder cancer cohort, we identified biomarkers that can predict treatment responsiveness. Given their challenging nature to detect using conventional methods, we are aiming to develop simpler detection techniques in the future. Furthermore, within the same cohort's multi-omics analysis, we discovered that cases positive for fusion genes or genetic mutations in the FGFR3 gene exhibited a certain characteristic, indicating the efficacy of immune checkpoint inhibitors. Through close collaboration with the Institute's Genomic Analysis Platform Development Division, we developed IRAVNet, a tool that comprehensively detects variants causing splicing abnormalities within the gene itself. By analyzing around 230,000 data points, we successfully identified approximately 27,000 variants. In addition, we have published two review articles and authored five books. Furthermore, Akihide Yoshimi delivered 15 invited lectures and received awards such as the Biotechnology Industry Organization Encouragement Award, the American Society of Hematology (ASH) Global Research Award, the Japanese Cancer Association JCA-Mauvernay Award, and the RIKEN Research Award.
Education
Continuing from the previous fiscal year, we welcomed trainees from the Central Hospital Laboratory and offered guidance in basic experiments. One foreign student was selected as a Japan Society for the Promotion of Science (JSPS) Foreign Special Research Fellow, one doctoral program graduate student became a JSPS Special Research Fellow (DC1), and another doctoral program graduate student was awarded the scholarship from the Futaba Electronics Memorial Foundation. These students have commenced their research in our laboratory.
Furthermore, we have been mentoring graduate students from various institutions: two from the University of Tokyo Graduate School, one from Tokyo Medical and Dental University Graduate School, and another from Tokyo Jikei University School of Medicine Graduate School. We have also welcomed a trainee from Osaka Medical and Pharmaceutical University. The training initiative for students from Tokyo Biotechnology Technical School, started in the 2021 fiscal year, concluded successfully at the end of this fiscal year, with these students graduating. Akihide Yoshimi has assumed the position of Visiting Professor at the Graduate School of Science at Kitasato University, contributing to talent development and education as a collaborating faculty member between Kitasato University and NCC. In April 2022, Akihide Yoshimi served as an organizing committee member for the Institute's Open Campus event, overseeing its execution. He also served as the organizer and chair of the "Advantages of Studying Abroad" session at the annual meeting of the Japan Society for Molecular Biology.
Future Prospects
In 2023, with the addition of two senior researchers, a Japan Society for the Promotion of Science (JSPS) Postdoctoral Fellow (PD), and two graduate students, we aim to create an even more enriching research environment. Building upon our cumulative research efforts, we intend to advance cancer research across various domains. Notably, the identification of novel, effective cross-cancer biomarkers from our research in the fiscal year 2022 has inspired us to further collaborate with the Central Hospital. This collaboration will serve to drive our research forward.
Furthermore, in 2023, we plan to propose physician-initiated trials originating from our research institute. We also aspire to enhance collaboration between the research institute and the Central Hospital, as well as forging stronger connections across our campuses in Kashiwa and Tsuruoka.
List of papers published in 2022
Journal
1. Shiraishi Y, Okada A, Chiba K, Kawachi A, Omori I, Mateos RN, Iida N, Yamauchi H, Kosaki K, Yoshimi A. Systematic identification of intron retention associated variants from massive publicly available transcriptome sequencing data. Nature communications, 13:5357, 2022
2. Yamauchi H, Nishimura K, Yoshimi A. Aberrant RNA splicing and therapeutic opportunities in cancers. Cancer science, 113:373-381, 2022
3. Hai Y, Kawachi A, He X, Yoshimi A. Pathogenic Roles of RNA-Binding Proteins in Sarcomas. Cancers, 14:3812, 2022
4. Oishi A, Jockers R. Measuring Protein-Protein Interactions of Melatonin Receptors by Bioluminescence Resonance Energy Transfer (BRET). Methods in molecular biology (Clifton, N.J.), 2550:207-218, 2022
5. Oishi A, Jockers R. Recent advances in orphan GPCRs research and therapeutic potential. GPCRs as Therapeutic Targets, 1:20-59, 2022
Book
1. Kurikawa M, Sakumoto M, Yoshimi A. 5. Perspective Chapter: RNA Therapeutics for Cancers. In: Vlasova I (ed), RNA therapeutics-history, design, manufacturing, and applications, US, IntechOpen, 2023