Annual Report 2020
Laboratory of Cancer RNA Research
Akihide Yoshimi, Ikuko Omori, Xiaohui Song, Hanako Nakamura, Michiko Kurikawa, Hirofumi Yamauchi, Atsuro Oishi, Takahiro Nishino
Introduction
The history of our lab started on July 1st, 2020. Our basic research is focused on aberrant RNA splicing in cancers, deorphanization, and the structure of ALK family receptors.
The Team and What We Do
Our lab members include one postdoctoral fellow, three visiting scientists, one student from the main hospital at NCC, and two technicians. Our team aims to understand and target aberrant RNA splicing in cancers.
Research activities
We have almost done with the setup of our own lab to start our scientific journey to (1) understand and target aberrant RNA splicing in cancers, (2) deorphanize and target orphan receptors, and (3) clarify the structural basis of ALK family receptors and their ligands. In particular, we have successfully dissected the 3D structures of ALK family receptors and clarified how cancer-associated ALK mutations increase the sensitivity of its ligand based on the 3D structure of combined ALK and its ligand. This work will be accepted by Nature and will soon be published. We have also identified that mutations in gene X create global splicing alterations in gliomas although gene X has no direct correlation with splicing or RNA. We will address why these mutations cause global splicing alterations, whether these splicing changes are important for disease pathogenesis, and whether the alterations in splicing create therapeutic vulnerabilities in gliomas.
Education
We accepted one clinical fellow from the main hospital of the NCC.
Future Prospects
Our lab is ready to start our own projects focusing on aberrant RNA splicing in cancers as well as deorphanization of orphan receptors to identify novel pathogenic mechanisms across cancers and to therapeutically target cancers with aberrant splicing or cancers with activated orphan receptors.
List of papers published in 2020
Journal
1 Liu Z, Yoshimi A, Wang J, Cho H, Chun-Wei Lee S, Ki M, Bitner L, Chu T, Shah H, Liu B, Mato AR, Ruvolo P, Fabbri G, Pasqualucci L, Abdel-Wahab O, Rabadan R. Mutations in the RNA Splicing Factor SF3B1 Promote Tumorigenesis through MYC Stabilization. Cancer Discov. 2020 Jun;10(6):806-821. doi: 10.1158/2159-8290.CD-19-1330. PMID: 32188705.
2 Yoshimi A, Trippett TM, Zhang N, Chen X, Penson AV, Arcila ME, Pichardo J, Baik J, Sigler A, Harada H, Fajgenbaum DC, Dogan A, Abdel-Wahab O, Xiao W. Genetic basis for iMCD-TAFRO. Oncogene. 2020 Apr;39(15):3218-3225. doi: 10.1038/s41388-020-1204-9.
3 Takaoka K, Koya J, Yoshimi A, Toya T, Kobayashi T, Nannya Y, Nakazaki K, Arai S, Ueno H, Usuki K, Yamashita T, Imanishi D, Sato S, Suzuki K, Harada H, Manabe A, Hayashi Y, Miyazaki Y, Kurokawa M. Nationwide epidemiological survey of familial myelodysplastic syndromes/acute myeloid leukemia in Japan: a multicenter retrospective study. Leuk Lymphoma. 2020 Mar 11;1-7. doi: 10.1080/10428194.2020.1734595. PMID: 32157945.
4 Maki H, Yoshimi A, Shimada T, Arai S, Morita K, Kamikubo Y, Ikegawa M, Kurokawa M. Physical interaction between BAALC and DBN1 induces chemoresistance in leukemia. Exp Hematol. 2021 Feb;94:31-36. doi: 10.1016/j.exphem.2020.12.003. PMID: 33453340.