Kyushu University Academic Staff Educational and Research Activities Database
List of Papers
Takahiro Maeda Last modified date:2020.04.13

Professor / Division of Precision Medicine / Department of Clinical Medicine / Faculty of Medical Sciences


Papers
1. Takuji Yamauchi,Takeshi Masuda,Matthew C. Canver,Michael Seiler,Yuichiro Semba, Mohammad Shboul,Mohammed Al-Raqad,Manami Maeda,Vivien A.C. Schoonenberg,Mitchel A. Cole,Claudio Macias-Trevino,Yuichi Ishikawa,Qiuming Yao,Michitaka Nakano,Fumio Arai,Stuart H. Orkin,Bruno Reversade,Silvia Buonamici,Luca Pinello,Koichi Akashi,Daniel E. Bauer and Takahiro Maeda , Genome-wide CRISPR-Cas9 Screen Identifies Leukemia-Specific Dependence on a Pre-mRNA Metabolic Pathway Regulated by DCPS, Cancer Cell, 2018.03, [URL], To identify novel targets for acute myeloid leukemia (AML) therapy, we performed genome-wide CRISPR-Cas9 screening using AML cell lines, followed by a second screen in vivo. Here, we show that the mRNA decapping enzyme scavenger (DCPS) gene is essential for AML cell survival. The DCPS enzyme interacted with components of pre-mRNA metabolic pathways, including spliceosomes, as revealed by mass spec- trometry. RG3039, a DCPS inhibitor originally developed to treat spinal muscular atrophy, exhibited anti-leukemic activity via inducing pre-mRNA mis-splicing. Humans harboring germline biallelic DCPS loss- of-function mutations do not exhibit aberrant hematologic phenotypes, indicating that DCPS is dispensable for human hematopoiesis. Our findings shed light on a pre-mRNA metabolic pathway and identify DCPS as a target for AML therapy..
2. Takeshi Masuda, Xin Wang, Manami Maeda, Matthew C. Canver, Falak Sher, Alister P. W. Funnell, Chris Fisher, Maria Suciu, Gabriella E. Martyn, Laura J. Norton, Catherine Zhu, Ryo Kurita, Yukio Nakamura, Jian Xu, Douglas R. Higgs, Merlin Crossley, Daniel E. Bauer, Stuart H. Orkin, Peter V. Kharchenko, Takahiro Maeda, Transcription factors LRF and BCL11A independently repress expression of fetal hemoglobin., Science, 2016.01, [URL], Genes encoding human β-type globin undergo a developmental switch from embryonic- to fetal- to adult-type. Mutations in the adult forms cause inherited hemoglobinopathies, or globin disorders, including sickle cell disease (SCD) and thalassemia, which some have suggested could be treated by re-induction of fetal-type hemoglobin (HbF). However, mechanisms that repress HbF in adults remain unclear. Here, we show that the LRF/ZBTB7A transcription factor occupies fetal γ-globin genes and maintains nucleosome density necessary for γ-globin gene silencing in adults. LRF confers its repressive activity through a NuRD repressor complex independent of the fetal globin repressor BCL11A. Our study may provide additional opportunities for therapeutic targeting in the treatment of hemoglobinopathies..