Kyushu University Academic Staff Educational and Research Activities Database
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Takahiro Maeda Last modified date:2019.06.19

Associate Professor / Department of Medicine and Biosystemic Science
Center for Cellular and Molecular Medicine
Kyushu University Hospital


Graduate School
Other Organization


Academic Degree
MD., Ph.D.
Country of degree conferring institution (Overseas)
No
Field of Specialization
Hematology/Oncology
ORCID(Open Researcher and Contributor ID)
orcid.org/0000-0003-4530-6460
Total Priod of education and research career in the foreign country
15years01months
Research
Research Interests
  • Goals of our research projects are to:
    1. Identify novel targets for acute myeloid leukemia (AML) therapy.
    2. Determine molecular mechanisms underlying fetal global repression in adult erythroid cells.
    3. Determine the role of the transcription factor LRF/ZBTB7A in hematopoietic cellular differentiation.
    keyword : Acute myeloid leukemia, Sickle cell disease, Differentiation of hematopoietic lineage cells
    2016.10.
Current and Past Project
  • Hemoglobinopathies, such as sickle cell disease (SCD) and thalassemia, are among the greatest public health concerns in the world. Although new therapeutic modalities, such as gene therapy, are currently being tested, there is a pressing need for pharmacologic approaches to treat general patient populations. Our long-term goal is to develop a compound(s) that induces fetal-type globin (HbF) production by targeting the transcriptional complex regulating globin switching. The objective of this application is to determine molecular mechanisms underlying the LRF-NuRD-mediated γ-globin silencing and identify a mean(s) to target them. Our central hypothesis is that the LRF-containing NuRD complex is a potential target for HbF reactivation therapy. The rationale for the proposed research is that understanding the LRF/NuRD-mediated globin regulation will provide greater understanding of the transcriptional complex regulating γ-globin repression and facilitate development of novel therapeutic strategies for HbF induction therapy.
  • Goal of this study is to identify novel targets for leukemia therapy using a genome-wide CRISPR/Cas9 screen.
Academic Activities
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..
Membership in Academic Society
  • Japan Society for Hematopoietic Cell Transplantation