Annual Report 2023
Division of Cancer RNA Research
Akihide Yoshimi, Tomoya Muto, Masahiko Ajiro, Asuka Kawachi, Kazuki Nishimura, Atsuhito Nakayama, Guzhanuer Ailiken, Mina Yoshida, Rei Kudo, Hai Yu, Marimu Sakumoto, Mayumi Hanzawa, Natsuko Shinohara, Ayano Go, Kaori Sakuma, Ryoichi Maenosono, Michiko Kurikawa, Hirofumi Yamauchi, Atsuro Oishi, Satoshi Kaito, Takahiro Nishino, Tetsuro Takasaki, Kiyono Nobayashi
Introduction
We started our lab on July 1st, 2020, to focus on aberrant RNA splicing across cancers, deorphanization of G-protein coupled receptors, and the development of nucleic acid therapeutics for cancers.
The Team and What We Do
Two senior staff scientists, one special researcher (CPD) from the Japan Society for the Promotion of Science, three scientist researchers, and one graduate school student newly joined our laboratory. They promoted research in various areas including elucidation of the mechanisms of carcinogenesis due to RNA splicing abnormalities in cancer, development of nucleic acid therapeutics for cancer, omics analysis using large-scale patient cohort data, pathological analysis of hematologic tumors, and development of cancer therapies targeting GPCR. Additionally, Akihide Yoshimi's research project was selected for the Challenging Research (Pioneering) category by the Grants-in-Aid for Scientific Research (KAKENHI), and research has commenced. We continued to advance ongoing projects from the previous fiscal year, such as the AMED Drug Discovery Support Network Program, AMED Next-Generation Cancer Therapy Acceleration Research Project, AMED Translational Research Program Seed A, JST Emergent Research Support Project, and Basic Research (A) (KAKENHI).
Research Activities
Large-scale cohort analysis of bladder cancer revealed diversity in the tumor immune microenvironment among cases with FGFR3 mutations, identifying some types that are susceptible to immune checkpoint inhibitors. The findings were published in Molecular Cancer. Additionally, 12 academic papers were reported, and 6 books were published. The lab collectively delivered 40 presentations at academic conferences, including 10 invited lectures by Akihide Yoshimi. Tomoya Muto received the UJA Paper Award 2023, and Kazuki Nishimura received the Best Presentation Award at the 254th Kansai Regional Meeting of the Japanese Urological Association.
Education
One doctoral student was accepted as a Japan Society for the Promotion of Science Special Research Fellow (DC2) and began research in this laboratory. Additionally, one postgraduate doctoral student from the Jikei University Graduate School of Medicine was accepted and mentored. Akihide Yoshimi, continuing from the previous year, served as a visiting professor at the Graduate School of Science, Kitasato University, where he lectured students and supervised doctoral theses. This year, he was newly appointed as a collaborating professor at Hiroshima University, and he mentored voluntary trainees from the Hiroshima University School of Medicine. The student received an excellence award at the medical research training presentation after the training.
Future Prospects
In addition to various studies on cancer splicing anomalies that have been conducted so far, we plan to initiate new research in 2023 themed on the development of precision cancer immunotherapy. Furthermore, we aim to advance various research and development initiatives, including preclinical trials using the NCC J-PDX library, molecular biological analysis using live cells derived from the same PDX model, data utilization through the expansion of multiplex immunofluorescence staining data of the Pathology Department's Tissue microarray cohort, collaboration with a whole genome analysis project, joint research with the Kashiwa campus, and envisaging joint research with pharmaceutical companies.
List of papers published in 2023
Journal
1. Yamauchi H, Momoki M, Kamiyama Y, Gunji T, Yokoyama H, Saito T, Boutboul D, Oksenhendler E, Yano S. Hodgkin Lymphoma-related Inflammatory Modification-displayed Castleman Disease-like Histological Features and Positron Emission Tomography/Computed Tomography Usefulness for the Differential Diagnosis. Internal medicine (Tokyo, Japan), 63:993-998, 2024
2. Yamada M, Maeta K, Suzuki H, Kurosawa R, Takenouchi T, Awaya T, Ajiro M, Takeuchi A, Nishio H, Hagiwara M, Miya F, Matsuo M, Kosaki K. Successful skipping of abnormal pseudoexon by antisense oligonucleotides in vitro for a patient with beta-propeller protein-associated neurodegeneration. Scientific reports, 14:6506, 2024
3. Igarashi T, Mazevet M, Yasuhara T, Yano K, Mochizuki A, Nishino M, Yoshida T, Yoshida Y, Takamatsu N, Yoshimi A, Shiraishi K, Horinouchi H, Kohno T, Hamamoto R, Adachi J, Zou L, Shiotani B. An ATR-PrimPol pathway confers tolerance to oncogenic KRAS-induced and heterochromatin-associated replication stress. Nature communications, 14:4991, 2023
4. Komura K, Tokushige S, Ishida M, Hirosuna K, Yamazaki S, Nishimura K, Ajiro M, Ohno T, Nakamori K, Kinoshita S, Tsujino T, Maenosono R, Yoshikawa Y, Takai T, Tsutsumi T, Taniguchi K, Tanaka T, Takahara K, Inamoto T, Hirose Y, Ono F, Shiraishi Y, Yoshimi A, Azuma H. Tertiary lymphoid structure and neutrophil-lymphocyte ratio coordinately predict outcome of pembrolizumab. Cancer science, 114:4622-4631, 2023
5. Komura K, Hirosuna K, Tokushige S, Tsujino T, Nishimura K, Ishida M, Hayashi T, Ura A, Ohno T, Yamazaki S, Nakamori K, Kinoshita S, Maenosono R, Ajiro M, Yoshikawa Y, Takai T, Tsutsumi T, Taniguchi K, Tanaka T, Takahara K, Konuma T, Inamoto T, Hirose Y, Ono F, Shiraishi Y, Yoshimi A, Azuma H. The Impact of FGFR3 Alterations on the Tumor Microenvironment and the Efficacy of Immune Checkpoint Inhibitors in Bladder Cancer. Molecular cancer, 22:185, 2023
6. Yoshida M, Matsuda K, Taoka K, Honda A, Maki H, Masamoto Y, Jona M, Nishikawa M, Yatomi Y, Kurokawa M. Expansion of large granular lymphocytes after autologous hematopoietic stem cell transplantation. International journal of hematology, 117:839-844, 2023
7. Shibamiya A, Miyamoto-Nagai Y, Koide S, Oshima M, Rizq O, Aoyama K, Nakajima-Takagi Y, Kato R, Kayamori K, Isshiki Y, Oshima-Hasegawa N, Muto T, Tsukamoto S, Takeda Y, Koyama-Nasu R, Chiba T, Honda H, Yokote K, Iwama A, Sakaida E, Mimura N. The pathogenetic significance of exhausted T cells in a mouse model of mature B cell neoplasms. Cancer immunology, immunotherapy, 72:2635-2648, 2023
8. Muto T, Walker CS, Agarwal P, Vick E, Sampson A, Choi K, Niederkorn M, Ishikawa C, Hueneman K, Varney M, Starczynowski DT. Inactivation of p53 provides a competitive advantage to del(5q) myelodysplastic syndrome hematopoietic stem cells during inflammation. Haematologica, 108:2715-2729, 2023
9. Kurosawa R, Iida K, Ajiro M, Awaya T, Yamada M, Kosaki K, Hagiwara M. PDIVAS: Pathogenicity predictor for Deep-Intronic Variants causing Aberrant Splicing. BMC genomics, 24:601, 2023
10. Ma HL, Bizet M, Soares Da Costa C, Murisier F, de Bony EJ, Wang MK, Yoshimi A, Lin KT, Riching KM, Wang X, Beckman JI, Arya S, Droin N, Calonne E, Hassabi B, Zhang QY, Li A, Putmans P, Malbec L, Hubert C, Lan J, Mies F, Yang Y, Solary E, Daniels DL, Gupta YK, Deplus R, Abdel-Wahab O, Yang YG, Fuks F. SRSF2 plays an unexpected role as reader of m(5)C on mRNA, linking epitranscriptomics to cancer. Molecular cell, 83:4239-4254.e10, 2023
11. Maenosono R. Sex difference and immunosenescence affect transplantation outcomes. Frontiers in Transplantation, 2:2023