Updated on 2024/12/24

写真a

 
MAGARI Masaki
 
Organization
Faculty of Interdisciplinary Science and Engineering in Health Systems Assistant Professor
Position
Assistant Professor
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Degree

  • Doctor(Engineering) ( Okayama University )

Research Interests

  • B cell

  • Follicular dendritic cell

  • Cell Biology

  • Immunology

  • Germinal center

  • 細胞生物学

  • 機能生物学

  • Functional Biochemistry

  • 免疫学

Research Areas

  • Life Science / Functional biochemistry

  • Life Science / Immunology

  • Manufacturing Technology (Mechanical Engineering, Electrical and Electronic Engineering, Chemical Engineering) / Biofunction and bioprocess engineering

Education

  • Okayama University    

    - 2002

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  • Okayama University   自然科学研究科   システム科学専攻

    - 2002

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    Country: Japan

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  • Okayama University    

    - 1998

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  • Okayama University   工学部   生物応用工学科

    - 1998

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    Country: Japan

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Research History

  • - Assistant Professor,Graduate School of Natural Science and Technology,Okayama University

    2002

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  • - 岡山大学自然科学研究科 助教

    2002

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Professional Memberships

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Papers

  • Development of a novel AAK1 inhibitor via Kinobeads-based screening. Reviewed International journal

    Akari Yoshida, Satomi Ohtsuka, Fumiya Matsumoto, Tomoyuki Miyagawa, Rei Okino, Yumeya Ikeda, Natsume Tada, Akira Gotoh, Masaki Magari, Naoya Hatano, Ryo Morishita, Ayano Satoh, Yukinari Sunatsuki, Ulf J Nilsson, Teruhiko Ishikawa, Hiroshi Tokumitsu

    Scientific reports   14 ( 1 )   6723 - 6723   2024.3

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    Language:English   Publishing type:Research paper (scientific journal)  

    A chemical proteomics approach using Ca2+/calmodulin-dependent protein kinase kinase (CaMKK) inhibitor-immobilized sepharose (TIM-063-Kinobeads) identified main targets such as CaMKKα/1 and β/2, and potential off-target kinases, including AP2-associated protein kinase 1 (AAK1), as TIM-063 interactants. Because TIM-063 interacted with the AAK1 catalytic domain and inhibited its enzymatic activity moderately (IC50 = 8.51 µM), we attempted to identify potential AAK1 inhibitors from TIM-063-derivatives and found a novel AAK1 inhibitor, TIM-098a (11-amino-2-hydroxy-7H-benzo[de]benzo[4,5]imidazo[2,1-a]isoquinolin-7-one) which is more potent (IC50 = 0.24 µM) than TIM-063 without any inhibitory activity against CaMKK isoforms and a relative AAK1-selectivity among the Numb-associated kinases family. TIM-098a could inhibit AAK1 activity in transfected cultured cells (IC50 = 0.87 µM), indicating cell-membrane permeability of the compound. Overexpression of AAK1 in HeLa cells significantly reduced the number of early endosomes, which was blocked by treatment with 10 µM TIM-098a. These results indicate TIM-063-Kinobeads-based chemical proteomics is efficient for identifying off-target kinases and re-evaluating the kinase inhibitor (TIM-063), leading to the successful development of a novel inhibitory compound (TIM-098a) for AAK1, which could be a molecular probe for AAK1. TIM-098a may be a promising lead compound for a more potent, selective and therapeutically useful AAK1 inhibitor.

    DOI: 10.1038/s41598-024-57051-9

    PubMed

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  • Transcriptional, biochemical, and immunohistochemical analyses of CaMKKβ/2 splice variants that co-localize with CaMKIV in spermatids Reviewed

    Satomi Ohtsuka, Yumi Miyai, Hiroyuki Mima, Masaki Magari, Yoichi Chiba, Futoshi Suizu, Hiroyuki Sakagami, Masaki Ueno, Hiroshi Tokumitsu

    Cell Calcium   102820 - 102820   2024.1

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    Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    DOI: 10.1016/j.ceca.2023.102820

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  • Rapid detection of calmodulin/target interaction via the proximity biotinylation method. Reviewed International journal

    Kento Nlandu Nakamura, Haruki Yamauchi, Hiroyuki Mima, Yerun Chen, Satomi Ohtsuka, Masaki Magari, Ryo Morishita, Hiroshi Tokumitsu

    Biochemical and biophysical research communications   659   29 - 33   2023.4

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    Language:English   Publishing type:Research paper (scientific journal)  

    Calmodulin (CaM) is known to function as a central signal transducer in calcium-mediated intracellular pathways. In this study, a fusion molecule of a recently developed proximity biotinylation enzyme (AirID) with rat CaM (AirID-CaM) was expressed and purified to near homogeneity using an E. coli expression system to examine the physical interactions between CaM and its target proteins by converting the interaction to biotinylation of CaM targets under nondenatured conditions. AirID-CaM catalyzed a Ca2+-dependent biotinylation of a target protein kinase (Ca2+/CaM-dependent protein kinase kinase α/1, CaMKKα/1) in vitro, which was suppressed by the addition of excess amounts of CaM, and AirID alone did not catalyze the biotinylation of CaMKKα/1, indicating that the biotinylation of CaMKKα/1 by AirID-CaM likely occurs in an interaction-dependent manner. Furthermore, we also observed the Ca2+-dependent biotinylation of GST-CaMKIα and GST-CaMKIV by AirID-CaM, suggesting that AirID-CaM can be useful for the rapid detection of CaM/target interactions with relatively high sensitivity.

    DOI: 10.1016/j.bbrc.2023.03.072

    PubMed

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  • The immunoreceptor SLAMF8 promotes the differentiation of follicular dendritic cell-dependent monocytic cells with B cell-activating ability. Reviewed International journal

    Masaki Magari, Miku Nishioka, Tomomi Hari, Sayaka Ogawa, Kaho Takahashi, Naoya Hatano, Naoki Kanayama, Junichiro Futami, Hiroshi Tokumitsu

    FEBS letters   2022.8

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    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    Follicular dendritic cells (FDCs) play a crucial role in generating high-affinity antibody-producing B cells during the germinal center (GC) reaction. Herein, we analysed the altered gene expression profile of a mouse FDC line, FL-Y, following lymphotoxin β receptor stimulation, and observed increased Slam-family member 8 (Slamf8) mRNA expression. Forced Slamf8 expression and SLAMF8-Fc addition enhanced the ability of FL-Y cells to induce FDC-induced monocytic cell (FDMC) differentiation. FDMCs accelerated GC-phenotype proliferation in cultured B cells, suggesting that they are capable of promoting GC responses. Furthermore, a pulldown assay showed that SLAMF8-Fc could bind to SLAMF8-His. Overall, the homophilic interaction of SLAMF8 promotes FDMC differentiation and SLAMF8 might act as a novel regulator of GC responses by regulating FDMC differentiation.

    DOI: 10.1002/1873-3468.14468

    PubMed

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  • Substrate recognition by Arg/Pro‐rich insert domain in calcium/calmodulin‐dependent protein kinase kinase for target protein kinases Reviewed

    Riku Kaneshige, Satomi Ohtsuka, Yuhei Harada, Issei Kawamata, Masaki Magari, Naoki Kanayama, Naoya Hatano, Hiroyuki Sakagami, Hiroshi Tokumitsu

    The FEBS Journal   2022.5

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    Publishing type:Research paper (scientific journal)   Publisher:Wiley  

    DOI: 10.1111/febs.16467

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MISC

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Presentations

  • BAFFはB細胞活性化能を有する単球系細胞の分化を促進する

    森 紀華, 中塚 梨沙, 大塚 里美, 徳光 浩, 曲 正樹

    第47回日本分子生物学会年会  2024.11.29 

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    Event date: 2024.11.27 - 2024.11.29

    Presentation type:Poster presentation  

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  • 濾胞樹状細胞の発現するSLAMF5によるB細胞の機能調節

    曲 正樹,高橋 佳歩,西岡 美玖,大塚 里美,徳光 浩

    第47回日本分子生物学会年会  2024.11.29 

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    Event date: 2024.11.27 - 2024.11.29

    Presentation type:Poster presentation  

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  • CaMKKオリゴマー形成の分子機構

    上野山 駿, 日多 勇人, 大塚 里美, 曲 正樹, 徳光 浩

    第47回日本分子生物学会年会  2024.11.27 

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    Event date: 2024.11.27 - 2024.11.29

    Presentation type:Poster presentation  

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  • B細胞活性化能を有する単球系細胞の分化機構の解明

    曲 正樹, 森 紀華, 西岡 美玖, 中塚 梨紗, 小川 紗也香, 大塚 里美, 徳光 浩

    第97回 日本生化学会大会  2024.11.8 

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    Event date: 2024.11.6 - 2024.11.8

    Presentation type:Poster presentation  

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  • CaMKKβの新たな酵素活性調節機構の解明に向けた生化学的解析

    大塚 里美, 波多野 直哉, 曲 正樹, 徳光 浩

    第97回 日本生化学会大会  2024.11.6 

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    Event date: 2024.11.6 - 2024.11.8

    Presentation type:Oral presentation (general)  

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Industrial property rights

  • B細胞の抗体遺伝子変異様式の転換方法

    大森 齊, 金山 直樹, 曲 正樹

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    Applicant:国立大学法人 岡山大学

    Application no:特願2007-231741  Date applied:2007.9.6

    Announcement no:特開2009-060850  Date announced:2009.3.26

    J-GLOBAL

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Awards

  • ベストティーチャー賞

    2024.3   岡山大学工学部  

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  • 社会貢献賞

    2023.3   岡山大学工学部  

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  • 科学技術賞

    2019   岡山工学振興会  

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  • 生物学研究奨励賞

    2019  

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  • 生物学研究奨励賞

    2015   両備てい園  

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    Country:Japan

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Research Projects

  • 抗体産生を促進する因子探索からワクチン強化技術への展開

    Grant number:24K08171  2024.04 - 2027.03

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    曲 正樹

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    Grant amount:\4680000 ( Direct expense: \3600000 、 Indirect expense:\1080000 )

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  • 抗体産生を増強する因子探索によるワクチン強化技術への展開

    2023.06 - 2025.05

    公益財団法人ウエスコ学術振興財団  研究助成金 

    曲 正樹

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\920000

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  • 抗体産生を増強する因子解明によるワクチン強化技術の開発

    2022.08 - 2023.03

    岡山大学大学院ヘルスシステム統合科学研究科  統合科学研究プロジェクト経費 

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    Authorship:Principal investigator 

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  • 免疫機能を内包する人工リンパ節の構築

    2021.06 - 2022.05

    公益財団法人ウエスコ学術振興財団  研究助成金 

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    Authorship:Coinvestigator(s) 

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  • リンパ節由来ストローマ細胞株を用いる人工リンパ節構築系の開発

    Grant number:21K04791  2021.04 - 2024.03

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    曲 正樹

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    Grant amount:\4160000 ( Direct expense: \3200000 、 Indirect expense:\960000 )

    リンパ節は,体内に侵入した病原体 (抗原) に対する免疫応答を活性化するために重要な二次リンパ組織である.リンパ球は,血管とリンパ管を通して全身のリンパ組織を循環しているが,病原体が侵入した際には感染部位近傍のリンパ節で活性化し,ストローマ細胞の制御のもと抗原への免疫応答を開始する.本課題では,体内に病原体が侵入した際のリンパ節での免疫応答の動的変化を解析するため,リンパ組織の支持細胞であるストローマ細胞を利用し,生体内に免疫能力を備えたリンパ節構造を構築できるシステムを開発することを目的とした.そのため,以前に樹立したストローマ細胞株(FL-Y)を利用した.
    本年度は,FL-Y細胞のリンパ球支持機能を強化するため,B細胞活性化因子(BAFF)および遊走因子(CXCL13)遺伝子を導入したFL-Y細胞株を樹立した.細胞培養系を用いて遺伝子導入したFL-Y細胞株のB細胞に対する作用を評価したいところ,B細胞の生存維持能力および遊走活性が増加していた.さらに,B細胞の抗体産生量も増加も見られた.これらの結果は,BAFFとCXCL13の発現によりFL-Y細胞のB細胞活性化能力が向上することを示している.
    次に,ストローマ細胞の活性化状態において発現変動する遺伝子を調査した.ストローマ細胞は,リンホトトキシンβ受容体(LTβR)からの刺激に応答して活性化するため,FL-Y細胞を抗LTβR抗体で刺激し,マイクロアレイにより網羅的に遺伝子発現変化を解析した.その結果,B細胞活性化に関わる可能性のあるいくつかの分子の発現上昇を見出した.

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Class subject in charge

  • Advanced Internship for Interdisciplinary Medical Sciences and Engineering (2024academic year) Year-round  - その他

  • Technical English for Interdisciplinary Medical Sciences and Engineering (2024academic year) Late  - その他

  • Research Works for Interdisciplinary Medical Sciences and Engineering (2024academic year) Year-round  - その他

  • Research Works for Interdisciplinary Medical Sciences and Engineering (2024academic year) Year-round  - その他

  • Biotechnology Experiment 1 (2024academic year) Third semester  - 火5~8,金5~8

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Media Coverage

  • 体内で高機能な抗体が作られる仕組みを解明し免疫能力の向上を目指す

    岡山大学記者発表  2022.9.29

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    Author:Myself