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Annual Report 2021

Cancer RNA Research Unit

Guzhanuer Ailiken, Asuka Kawachi, Ikuko Omori, Xiaohui Song, Hanako Nakamura, Marimu Sakumoto, Atsuhito Nakayama, Michiko Kurikawa, Hirofumi Yamauchi, Kazuki Nishimura, Atsuro Oishi, Takahiro Nishino, Kota Otsuki

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

 Our lab members include one postdoctoral fellow, four graduate students, one student from the main hospital at the NCC, two technicians and one trainee. Our team aims to understand and target aberrant RNA splicing in cancers.

Research activities

 We have fully completed the setup of our own lab within two years to start our scientific journey toward (1) understanding and targeting aberrant RNA splicing in cancers (for which Akihide Yoshimi received the Global Research Award from the American Society of Hematolgy and Mauvernay Award from the Japanese Cancer Association), (2) deorphanizing and targeting orphan receptors, (3) clarifying the structural basis of ALK family receptors and their ligands, and (4) developing novel nucleic acid therapeutics for cancers (for which Akihide Yoshimi received the Japan Bioindustry Research Award from the Japan Bioindustry Association). We have successfully dissected the 3D structures of ALK family receptors and clarified how cancer-associated ALK mutations increase the sensitivity of their ligands based on the 3D structure of combined ALK and its ligands. This work was published in Nature. We have also identified that a splicing factor X causes global splicing alterations in gliomas. We will address whether these splicing changes are important for the disease pathogenesis, and whether the alterations in splicing create therapeutic vulnerabilities in gliomas.

Education

 We have accepted one clinical fellow from the main hospital of the NCC. In addition, we have four graduate students from the University of Tokyo, Jikei University, and Tokyo Medical and Dental University. One of them is a special fellow of the JSPS (Japan Society for the Promotion of Science, DC1) and another has received a research grant from the Japan Science Society. Furthermore, we have accepted a foreign researcher who is a foreign special fellow of the JSPS.

Future Prospects

 Our lab is fully ready to start our own projects focusing on aberrant RNA splicing in cancers as well as deorphanization of orphan receptors, development of nucleic acid therapeutics, and many other projects targeting cancers, all of which aim to identify novel pathogenic mechanisms across cancers and therapeutically target a variety of cancers.