Updated on 2022/11/25

写真b

 
HIGUCHI Maiko
 
*Items subject to periodic update by Rikkyo University (The rest are reprinted from information registered on researchmap.)
Affiliation*
College of Science Department of Life Science
Graduate School of Science Doctoral Program in Life Science
Graduate School of Science Master's Program in Life Science
Title*
Associate Professor
Degree
博士(工学) ( 東京大学 )
Research Theme*
  • 細胞増殖・細胞運動は様々な生命現象において重要な役割を果たしている。私達は、動物培養細胞とゼブラフィッシュをモデル系として細胞増殖・細胞運動の制御メカニズムを明らかにすることにより、「1つの受精卵から複雑な生命体が形成される仕組み」「ヒトが様々な病気に罹患する仕組み」を解き明かすことを目指している。

  • Campus Career*
    • 4 2021 - Present 
      College of Science   Department of Life Science   Associate Professor
    • 4 2021 - Present 
      Graduate School of Science   Master's Program in Life Science   Associate Professor
    • 4 2021 - Present 
      Graduate School of Science   Doctoral Program in Life Science   Associate Professor
    • 11 2017 - 3 2021 
      College of Science   Assistant Professor
     

    Research Areas

    • Life Science / Cell biology

    Research History

    • 4 2021 - Present 
      Rikkyo University   College of Science

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    • 11 2017 - 3 2021 
      RIKKYO UNIVERSITY   College of Science   Assistant Professor

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    • 4 2014 - 10 2017 
      東京大学   薬学部   助教

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    • 1 2013 - 3 2014 
      Max Planck Institute for Heart and Lung Research   研究員

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    • 1 2012 - 12 2012 
      University of California, San Francisco   研究員

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    • 4 2007 - 12 2011 
      東京大学   分子細胞生物学研究所   助教

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    • 9 2005 - 3 2007 
      東京大学   分子細胞生物学研究所   助手

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    • 4 2003 - 8 2005 
      東京大学   分子細胞生物学研究所   研究員

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    Education

    • - 3 2003 
      The University of Tokyo   Graduate School, Division of Engineering

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      Country: Japan

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    • - 3 2000 
      The University of Tokyo   Graduate School, Division of Engineering

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      Country: Japan

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    • - 3 1998 
      The University of Tokyo   Faculty of Engineering

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      Country: Japan

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    Papers

    • Maternal stress suppresses cell proliferation in the forebrain of zebrafish larvae Peer-reviewed

      Maiko Higuchi

      Genes to Cells25 ( 5 ) 350 - 357   2020

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

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    • PDK1-Akt pathway regulates radial neuronal migration and microtubules in the developing mouse neocortex Peer-reviewed

      Yasuhiro Itoh, Maiko Higuchi, Koji Oishi, Yusuke Kishi, Tomohiko Okazaki, Hiroshi Sakai, Takaki Miyata, Kazunori Nakajima, Yukiko Gotoh

      PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA113 ( 21 ) E2955 - E2964   5 2016

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      Language:English   Publishing type:Research paper (scientific journal)   Publisher:NATL ACAD SCIENCES  

      Neurons migrate a long radial distance by a process known as locomotion in the developing mammalian neocortex. During locomotion, immature neurons undergo saltatory movement along radial glia fibers. The molecular mechanisms that regulate the speed of locomotion are largely unknown. We now show that the serine/threonine kinase Akt and its activator phosphoinositide-dependent protein kinase 1 (PDK1) regulate the speed of locomotion of mouse neocortical neurons through the cortical plate. Inactivation of the PDK1-Akt pathway impaired the coordinated movement of the nucleus and centrosome, a microtubule-dependent process, during neuronal migration. Moreover, the PDK1-Akt pathway was found to control microtubules, likely by regulating the binding of accessory proteins including the dynactin subunit p150(glued). Consistent with this notion, we found that PDK1 regulates the expression of cytoplasmic dynein intermediate chain and light intermediate chain at a posttranscriptional level in the developing neocortex. Our results thus reveal an essential role for the PDK1-Akt pathway in the regulation of a key step of neuronal migration.

      DOI: 10.1073/pnas.1516321113

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    • The ASK family kinases differentially mediate induction of type I interferon and apoptosis during the antiviral response Peer-reviewed

      Tomohiko Okazaki, Maiko Higuchi, Kohsuke Takeda, Kiyoko Iwatsuki-Horimoto, Maki Kiso, Makoto Miyagishi, Hideyuki Yanai, Atsushi Kato, Mitsutoshi Yoneyama, Takashi Fujita, Tadatsugu Taniguchi, Yoshihiro Kawaoka, Hidenori Ichijo, Yukiko Gotoh

      SCIENCE SIGNALING8 ( 388 ) ra78   8 2015

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      Language:English   Publishing type:Research paper (scientific journal)   Publisher:AMER ASSOC ADVANCEMENT SCIENCE  

      Viral infection activates host defense mechanisms, including the production of type I interferon (IFN) and the apoptosis of infected cells. We investigated whether these two antiviral responses were differentially regulated in infected cells. We showed that the mitogen-activated protein kinase (MAPK) kinase kinase (MAPKKK) apoptosis signal-regulating kinase 1 (ASK1) was activated in cells by the synthetic double-stranded RNA analog polyinosinic: polycytidylic acid [poly(I:C)] and by RNA viruses, and that ASK1 played an essential role in both the induction of the gene encoding IFN-beta (IFNB) and apoptotic cell death. In contrast, we found that the MAPKKK ASK2, a modulator of ASK1 signaling, was essential for ASK1-dependent apoptosis, but not for inducing IFNB expression. Furthermore, genetic deletion of either ASK1 or ASK2 in mice promoted the replication of influenza A virus in the lung. These results indicated that ASK1 and ASK2 are components of the antiviral defense mechanism and suggested that ASK2 acts as a key modulator that promotes apoptosis rather than the type I IFN response. Because ASK2 is selectively present in epithelium-rich tissues, such as the lung, ASK2-dependent apoptosis may contribute to an antiviral defense in tissues with a rapid repair rate in which cells could be readily replaced.

      DOI: 10.1126/scisignal.aab1883

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    • NEDDylation controls the target specificity of E2F1 and apoptosis induction Peer-reviewed

      I. Aoki, M. Higuchi, Y. Gotoh

      ONCOGENE32 ( 34 ) 3954 - 3964   8 2013

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      Language:English   Publishing type:Research paper (scientific journal)   Publisher:NATURE PUBLISHING GROUP  

      The transcription factor E2F1 has pivotal roles in both cell proliferation and cell death, and is an important molecular target in cancer. Under proliferative conditions E2F1 induces the expression of genes that promote cell cycle progression, such as E2F2, whereas under proapoptotic conditions E2F1 induces expression of genes such as p73 that lead to apoptosis. The mechanism by which the apoptotic function of E2F1 is activated remains unclear, however. We now show that members of the E2F family are covalently conjugated with the ubiquitin-like modifier NEDD8. Overexpression of SENP8, a NEDD8-specific cysteine protease, resulted in deNEDDylation of E2F1 and promoted its transactivation activity at the p73 gene but not at the E2F2 gene. Knockdown of SENP8, on the other hand, attenuated p73 expression and apoptosis induced by E2F1 or by DNA damage. SENP8 also promoted the interaction between E2F1 and its cofactor Microcephalin 1, which is required for p73 induction. These results suggest that NEDDylation is a molecular trigger that modifies the target specificity of E2F1, and could have important implications for E2F1 regulation of apoptosis.

      DOI: 10.1038/onc.2012.428

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    • Mitochondrial localization of the antiviral signaling adaptor IPS-1 is important for its induction of caspase activation Peer-reviewed

      Tomohiko Okazaki, Maiko Higuchi, Yukiko Gotoh

      Genes to Cells18 ( 6 ) 493 - 501   6 2013

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

      The RIG-I-like receptor (RLR) family of intracellular receptors detects viral nucleic acids and transmits an antiviral signal through the adaptor IPS-1. IPS-1 activation triggers host defense mechanisms, including rapid production of type I interferon (IFN), such as IFN-β, and induction of apoptosis. IPS-1 is mainly localized to mitochondria, and this localization has been proposed to be essential for inducing production of type I IFN and IFN-stimulated genes (ISGs). However, the importance of this mitochondrial localization of IPS-1 in executing apoptosis has remained unclear. Here, using IPS-1 mutants that were directed to specific subcellular locations such as cytoplasm, plasma membrane and mitochondria, we found that IPS-1's localization to mitochondria is important to activate caspase, but not to signal for IFN-β gene induction. We also found that IPS-1 possesses a BH3-like motif, which is commonly found among members of the Bcl-2 family. Mutations within this motif promoted IPS-1-induced caspase activation, suggesting that this domain acts as an intrinsic inhibitor domain of apoptosis induction. These results establish that the mitochondrial location of IPS-1 is essential to its ability to induce apoptosis. © 2013 by the Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.

      DOI: 10.1111/gtc.12052

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    • Akt1 promotes focal adhesion disassembly and cell motility through phosphorylation of FAK in growth factor-stimulated cells Peer-reviewed

      Maiko Higuchi, Rina Kihara, Tomohiko Okazaki, Ichiro Aoki, Shiro Suetsugu, Yukiko Gotoh

      JOURNAL OF CELL SCIENCE126 ( 3 ) 745 - 755   2 2013

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      Language:English   Publishing type:Research paper (scientific journal)   Publisher:COMPANY OF BIOLOGISTS LTD  

      The crosstalk between spatial adhesion signals and temporal soluble signals is key in regulating cellular responses such as cell migration. Here we show that soluble growth factors enhance integrin signaling through Akt phosphorylation of FAK at Ser695 and Thr700. PDGF treatment or overexpression of active Akt1 in fibroblasts increased autophosphorylation of FAK at Tyr397, an essential event for integrin turnover and cell migration. Phosphorylation-defective mutants of FAK (S695A and T700A) underwent autophosphorylation at Tyr397 and promoted cell migration in response to the integrin ligand fibronectin, but importantly, not in response to PDGF. This study has unveiled a novel function of Akt as an 'ignition kinase' of FAK in growth factor signaling and may shed light on the mechanism by which growth factors regulate integrin signaling.

      DOI: 10.1242/jcs.112722

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    • Scaffolding function of PAK in the PDK1-Akt pathway Peer-reviewed

      Maiko Higuchi, Keisuke Onishi, Chikako Kikuchi, Yukiko Gotoh

      NATURE CELL BIOLOGY10 ( 11 ) 1356 - U257   11 2008

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      Language:English   Publishing type:Research paper (scientific journal)   Publisher:NATURE PUBLISHING GROUP  

      Many extracellular signals stimulate phosphatidylinositol-3- kinase, which in turn activates the Rac1 GTPase, the protein kinase Akt and the Akt Thr 308 upstream kinase PDK1. Active Rac1 stimulates a number of events, including substrate phosphorylation by a subgroup of the PAK family of kinases. The combined effects of Rac1, PDK1 and Akt are crucial for cell migration, growth, survival, metabolism and tumorigenesis. Here we show that Rac1 stimulates a second, kinase-independent function of PAK1. The PAK1 kinase domain serves as a scaffold to facilitate Akt stimulation by PDK1 and to aid recruitment of Akt to the membrane. PAK differentially activates subpopulations of Akt. These findings reveal scaffolding functions of PAK that regulate the efficiency, localization and specificity of the PDK1-Akt pathway.

      DOI: 10.1038/ncb1795

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    • JNK phosphorylates synaptotagmin-4 and enhances Ca2+-evoked release. Peer-reviewed

      Mori, Y, Higuchi, M, Hirabayashi, Y, Fukuda, M, Gotoh, Y

      EMBO J.27 ( 1 ) 76 - 87   9 1 2008

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      DOI: 10.1038/sj.emboj.7601935

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    • The PI3K-Akt pathway promotes microtubule stabilization in migrating fibroblasts. Peer-reviewed

      Onishi K, Higuchi M, Asakura T, Masuyama N, Gotoh Y

      Genes to cells : devoted to molecular & cellular mechanisms12 ( 4 ) 535 - 546   4 2007

    • Adenosine A2A receptor facilitates calcium-dependent protein secretion through the activation of protein kinase A and phosphatidylinositol-3 kinase in PC12 cells. Peer-reviewed

      Mori Y, Higuchi M, Masuyama N, Gotoh Y

      Cell structure and function29 ( 4 ) 101 - 110   12 2004

    • The phosphatidylinositol-3 kinase (PI3K)-Akt pathway suppresses neurite branch formation in NGF-treated PC12 cells. Peer-reviewed

      Higuchi M, Onishi K, Masuyama N, Gotoh Y

      Genes to cells : devoted to molecular & cellular mechanisms8 ( 8 ) 657 - 669   8 2003

    • Hydrolysis of Diribonucleoside Monophosphate Diesters Assisted by a Manganese(II) Complex Peer-reviewed

      Morio Yashiro, Maiko Higuchi, Makoto Komiyama, Youichi Ishii

      Bulletin of the Chemical Society of Japan76 ( 9 ) 1813 - 1817   2003

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    • Effect of Alkaline Earth Metal Ions on the Phosphodiester Hydrolysis of RNA Peer-reviewed

      Morio Yashiro, Maiko Higuchi, Yusuke Washizu, Makoto Komiyama

      Bulletin of the Chemical Society of Japan75 ( 8 ) 1843 - 1844   2002

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    • SWAP-70 is a guanine-nucleotide-exchange factor that mediates signalling of membrane ruffling Peer-reviewed International journal

      Masahiro Shinohara, Yoh Terada, Akihiro Iwamatsu, Azusa Shinohara, Naoki Mochizuki, Maiko Higuchi, Yukiko Gotoh, Sayoko Ihara, Satoshi Nagata, Hiroshi Itoh, Yasuhisa Fukui, Rolf Jessberger

      Nature416 ( 6882 ) 759 - 763   2002

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

      Phosphoinositide-3-OH kinase (PI(3)K), activated through growth factor stimulation, generates a lipid second messenger, phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3). PtdIns(3,4,5)P3 is instrumental in signalling pathways that trigger cell activation, cytoskeletal rearrangement, survival and other reactions. However, some targets of PtdIns(3,4,5)P3 are yet to be discovered. We demonstrate that SWAP-70, a unique signalling protein, specifically binds PtdIns(3,4,5)P3. On stimulation by growth factors, cytoplasmic SWAP-70, which is dependent on PI(3)K but independent of Ras, moved to cell membrane rearrangements known as ruffles. However, mutant SWAP-70 lacking the ability to bind PtdIns(3,4,5)P3 blocked membrane ruffling induced by epidermal growth factor or platelet-derived growth factor. SWAP-70 shows low homology with Rac-guanine nucleotide exchange factors (GEFs), and catalyses PtdIns(3,4,5)P3-dependent guanine nucleotide exchange to Rac. SWAP-70-deficient fibroblasts showed impaired membrane ruffling after stimulation with epidermal growth factor, and failed to activate Rac fully. We conclude that SWAP-70 is a new type of Rac-GEF which, independently of Ras, transduces signals from tyrosine kinase receptors to Rac.

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    • Akt mediates Rac/Cdc42-regulated cell motility in growth factor-stimulated cells and in invasive PTEN knockout cells Peer-reviewed

      Maiko Higuchi, Norihisa Masuyama, Yasuhisa Fukui, Akira Suzuki, Yukiko Gotoh

      Current Biology11 ( 24 ) 1958 - 1962   2001

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    Misc.

    • Metatranscriptome analyses indicate resource partitioning between diatoms in the field (vol 112, pg E2182, 2015)

      Yasuhiro Itoh, Maiko Higuchi, Koji Oishi, Yusuke Kishi, Tomohiko Okazaki, Hiroshi Sakai, Takaki Miyata, Kazunori Nakajima, Yukiko Gotoh

      PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA113 ( 25 ) E3587 - E3587   6 2016

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      Language:English   Publishing type:Other   Publisher:NATL ACAD SCIENCES  

      DOI: 10.1073/pnas.1608043113

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    • PIキナーゼ-Akt経路 Invited

      樋口 麻衣子

      生体の科学   2015

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      Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

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    • 新規翻訳後修飾による抗ウイルス応答分子IPS-1の機能の使い分け

      岡崎朋彦, 樋口麻衣子, 後藤由季子

      生化学   2011

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    • 新規翻訳後修飾による抗ウイルス応答分子IPS-1の機能の使い分け

      岡崎朋彦, 樋口麻衣子, 後藤由季子

      日本Cell Death学会学術集会プログラム抄録集20th   2011

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    • JNK/p38MAPK経路によるウイルス応答制御メカニズム

      岡崎朋彦, 樋口麻衣子, 武田弘資, 宮岸真, 加藤篤, 米山光俊, 藤田尚志, 一條秀憲, 後藤由季子

      生化学   2009

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    • スキャフォールド分子PAKによるAktの選択的機能制御

      樋口 麻衣子, 大西 啓介, 後藤 由季子

      実験医学   2009

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    • Aktの活性化因子と哺乳類における機能

      樋口 麻衣子, 後藤 由季子

      実験医学   2005

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    • PI3K-Akt経路による癌の悪性化

      樋口 麻衣子, 後藤 由季子

      実験医学   2003

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    Research Projects

    • Akt-EB2/RP1による微小管動態の新規制御メカニズムと細胞極性制御

      日本学術振興会  科学研究費助成事業 

      樋口 麻衣子

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      4 2018

      Grant type:Competitive

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    • 原癌遺伝子Aktによる微小管安定化を介した細胞極性制御メカニズムの解明

      日本学術振興会  科学研究費助成事業 

      樋口 麻衣子

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      4 2015 - 3 2018

      Grant type:Competitive

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    • スーパー制限酵素を用いたゲノム・マニュピュレーション工学の創成

      日本学術振興会  科学研究費助成事業 

      小宮山 真

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      4 2010 - 3 2015

      Grant type:Competitive

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    • 原癌遺伝子Aktによる細胞極性制御メカニズムの解明

      日本学術振興会  科学研究費助成事業 

      樋口 麻衣子

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      4 2011 - 3 2012

      Grant type:Competitive

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    • 原癌遺伝子Aktの選択的機能制御と創薬への応用

      日本学術振興会  科学研究費助成事業 

      樋口 麻衣子

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      4 2008 - 3 2009

      Grant type:Competitive

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    • Akt経路のよる癌悪性化メカニズムの解明と創薬への応用

      日本学術振興会  科学研究費助成事業 

      樋口 麻衣子

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      4 2006 - 3 2007

      Grant type:Competitive

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