Annual Report 2022
TEAM YOKOYAMA
Akihiko Yokoyama, Yosuke Komata, Hagumu Sato, Ikuko Yokoyama, Ayako Yokoyama, Kanae Ito
Introduction
Our focus is on molecular pathology of childhood cancers such as refractory leukemia.
The Team and What We Do
Our team investigate the molecular mechanisms of leukemia and Wilms tumor using mouse disease models, proteomics approaches, and epigenome analytical tools. We aim to identify novel molecular targets for drug development by elucidating the molecular mechanisms by which oncoproteins cause aberrant self-renewal.
Research Activities
We have revealed mechanisms by which oncoproteins cause aberrant self-renewal. We particularly focused on the functions of MOZ and MLL, both of which activate expression of the genes previously expressed in mother cells, thereby promoting self-renewal. Based on our findings, we have proposed novel therapeutic targets for refractory leukemia. Moreover, a molecularly targeted drug which we developed by collaborating with a pharmaceutical company is now in clinical trials in North America and Japan.
1. Becht DC, Klein BJ, Kanai A, Jang SM, Cox KL, Zhou BR, Phanor SK, Zhang Y1, Chen RW, Ebmeier CC, Lachance C, Galloy M, Fradet-Turcotte A, Bulyk ML, Bai Y, Poirier, MG, *Côté J, *Yokoyama A, and *Kutateladze TG. MORF and MOZ acetyltransferases target unmethylated CpG islands through the winged helix domain Nature Communications (2023)14:697
2. *Okuda H, Miyamoto M, Takahashi S, Kawamura T Ichikawa J, Harada I, Tamura T and *Yokoyama A. RNA-Binding Proteins of KHDRBS and IGF2BP families control the Oncogenic Activity of MLL-AF4 Nature Communications (2022) 13:6688
3. Shinriki S, Hirayama M, Nagamachi A, Yokoyama A, Kawamura T, Kanai A, Kawai H, Iwakiri J, Liu R, Maeshiro M, Tungalag S, Tasaki M, Ueda M, Tomizawa K, Kataoka N, Ideue T, Suzuki Y, Asai K, Tani T, Inaba T, and Matsui H. DDX41 coordinates RNA splicing and transcriptional elongation to prevent DNA replication stress in hematopoietic cells Leukemia (2022) 36:2605-2620
4. Isobe T, Takagi M, Sato-Otsubo A, Nishimura A, Nagae G, Yamagishi C, Tamura M, Tanaka Y, Asada S, Takeda R, Tsuchiya A, Wang X, Yoshida K, Nannya Y, Ueno H, Akazawa R, Kato I, Mikami T, Watanabe K, Sekiguchi M, Seki M, Kimura S, Hiwatari M, Kato M, Fukuda S, Tatsuno K, Tsutsumi S, Kanai A, Inaba T, Shiozawa Y, Shiraishi Y, Chiba K, Tanaka H, Kotecha RS, Cruickshank MN, Ishikawa F, Morio T, Eguchi M, Deguchi T, Kiyokawa N, Arakawa Y, Koh K, Aoki Y, Ishihara T, Tomizawa D, Miyamura T, Ishii E, Mizutani S, Wilson NK, Göttgens B, Miyano S, Kitamura T, Goyama S, Yokoyama A, Aburatani H, Ogawa S, Takita J. Multi-omics analysis defines highly refractory RAS burdened immature subgroup of infant acute lymphoblastic leukemia Nature Communications (2022) 13:4501
5. Koyauchi T, Niida H, Motegi A, Sakai S, Uchida C, Ohata T, Iijima K, Yokoyama A, Suda T, Kitagawa M. Chromatin-remodeling factor BAZ1/ACF1 targets UV damage sites in an MLL1-dependent manner to facilitate nucleotide excision repair. BBA-Molecular Cell Research (2022) 1869(11),119332
6. Tanaka A, Nakano T, Nomura M, Yamazaki H, Bewersdorf J, Mulet-Lazaro R, Hogg S, Liu B, Penson A, Yokoyama A, Zang W, Havermans M, Koizumi M, Hayashi Y, Cho H, Kanai A, Lee S, Xiao M, Koike Y, Zhang Y, Fukumoto M, Aoyama Y, Konuma T, Kunimoto H, Inaba T, Nakajima H, Honda H, Kawamoto H, Dell R, Abdel-Wahab O, Inoue D. Aberrant EVI1 splicing contributes to EVI1-rearrange
Clinical Trials
A novel drug for leukemia that we developed with Sumitomo Pharma is now in the phase I/II clinical trial in Canada, the US, and Japan. Since we are a basic research team, we are not engaged in the clinical trials.
Education
Researchers and technicians are being trained.
Future Prospects
We aim to identify novel therapeutic targets, which may lead to development of new therapies, through the deep understanding of the molecular mechanisms of childhood cancer.