Tago, Megumi

写真a

Affiliation

Faculty of Pharmacy, Department of Pharmacy 衛生化学講座 (Shiba-Kyoritsu)

Position

Professor
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Career 【 Display / hide 】

  • 2006.06
    -
    Present

    2003年4月～2006年5月 米国留学 2006年6月 共立薬科大学薬学部生化学講座　助手 (2007年４月より助教） 2008年4月 慶應義塾大学薬学部生化学講座　助教 2009年4月 慶應義塾大学薬学部生化学講座　専任講師 2014年4月 慶應義塾大学薬学部衛生化学講座 准教授

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Academic Background 【 Display / hide 】

  • 1998.03

    共立薬科大学, 薬学部, 薬学科

    University, Graduated

  • 2003.03

    共立薬科大学大学院, 薬学研究科, 分子生物学、生化学

    Graduate School, Completed, Doctoral course

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Academic Degrees 【 Display / hide 】

  • 博士（薬学）, 共立薬科大学, Coursework, 2003.03

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Research Areas 【 Display / hide 】

  • Life Science / Pharmaceutical hygiene and biochemistry (Biological System Pharmaceutical Science)

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Research Keywords 【 Display / hide 】

  • JAK2、STAT、erythropoietin、NF-kappaB

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Research Themes 【 Display / hide 】

  • Analysis of cytokine signaling pathway, 

    2006
    -
    Present

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Books 【 Display / hide 】

  • IL-33レセプターのシグナル伝達.

    笠原 忠、多胡めぐみ., 科学評論社, 2011.03

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Papers 【 Display / hide 】

  • The indispensable role of the RNA helicase DDX5 in tumorigenesis induced by the myeloproliferative neoplasm-associated JAK2V617F mutant

    Takeda K., Tago K., Funakoshi-Tago M.

    Cellular Signalling (Cellular Signalling)  102 2023.02

    ISSN  08986568

    　View Summary

    A point mutation (V617F) in the Janus kinase 2 (JAK2) gene results in the production of disorderly activated tyrosine kinase, which causes myeloproliferative neoplasms (MPN). We herein demonstrated that the RNA helicase DDX5 was highly expressed at the mRNA and protein levels through the activation of signal transducer and activator of transcription 5 (STAT5) in Ba/F3 cells expressing a JAK2V617F mutant and erythropoietin receptor (V617F/EpoR cells) and MPN patient-derived HEL cells. A treatment with the JAK1/2 inhibitor, ruxolitinib and STAT5 inhibitor, pimozide significantly inhibited DDX5 mRNA expression and enhanced the degradation of DDX5 in these cells, suggesting that the JAK2V617F mutant positively regulates DDX5 mRNA expression and DDX5 protein stability by activating STAT5. The knockdown of DDX5 specifically inhibited the activation of mechanistic target of rapamycin (mTOR) in V617F/EpoR cells and HEL cells and significantly suppressed the proliferation of these cells. Furthermore, the knockdown of DDX5 markedly suppressed tumorigenesis, splenomegaly, and liver hypertrophy caused by an inoculation of V617F/EpoR cells in nude mice. Collectively, these results revealed that JAK2V617F exhibits transforming activity by inducing the expression of DDX5 in a STAT5-dependent manner, indicating the potential of the JAK2V617F/STAT5/DDX5 axis as a therapeutic target in the treatment of MPN.

  • Identification of DDX5 as an indispensable activator of the glucocorticoid receptor in adipocyte differentiation.

    Hokimoto S, Funakoshi-Tago M, Tago K.

    FEBS J.   2022.09

    Research paper (scientific journal), Joint Work, Corresponding author, Accepted

  • Coffee ingredients, hydroquinone, pyrocatechol, and 4-ethylcatechol exhibit anti-inflammatory activity through inhibiting NF-κB and activating Nrf2

    Funakoshi-Tago M., Matsutaka M., Hokimoto S., Kobata K., Tago K., Tamura H.

    Journal of Functional Foods (Journal of Functional Foods)  90 2022.03

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  17564646

    　View Summary

    Pyrocatechol is a coffee ingredient that exhibits anti-inflammatory activity. We herein identified hydroquinone and 4-ethylcatechol as novel coffee ingredients inhibiting LPS-induced inflammatory responses. Similar to pyrocatechol, hydroquinone and 4-ethylcatechol significantly inhibited LPS-induced nitric oxide (NO) production and CCL2 secretion by suppressing the mRNA expression of iNOS and CCL2 in murine macrophage-like RAW264.7 cells. These ingredients also inhibited the LPS-induced activation of NF-κB, a pivotal transcription factor in inflammation, by preventing its nuclear localization, and induced the expression of Nrf2, a transcription factor negatively regulating LPS-induced inflammation. By utilizing Keap1−/−MEFs reconstituted with Keap1 mutants in which major cysteine residues were substituted, we found that Cys151 in Keap1 was a critical sensor for pyrocatechol, hydroquinone, and 4-ethylcatechol to induce Nrf2 expression. However, the amounts of hydroquinone and 4-ethylcatechol in the coffee decoction were markedly lower than that of pyrocatechol, suggesting that pyrocatechol is the main coffee ingredient exhibiting anti-inflammatory activity.

  • A bis-pyridinium fullerene derivative induces apoptosis through the generation of ROS in BCR-ABL-positive leukemia cells

    Sumi K., Tago K., Nakazawa Y., Takahashi K., Ohe T., Mashino T., Funakoshi-Tago M.

    European Journal of Pharmacology (European Journal of Pharmacology)  916 2022.02

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  00142999

    　View Summary

    A fusion protein, Breakpoint cluster region-Abelson (BCR-ABL) is responsible for the development of chronic myeloid leukemia (CML) and acute lymphocytic leukemia (ALL). Inhibitors against BCR-ABL are effective for the treatment of leukemia; however, a gatekeeper mutation (T315I) in BCR-ABL results in resistance to these inhibitors, which markedly impedes their efficacy. We herein demonstrated that a bis-pyridinium fullerene derivative (BPF) significantly induced apoptosis in human CML-derived K562 cells and ALL-derived SUP-B15 cells via the generation of reactive oxygen species (ROS). BPF reduced the expression of Bcr-Abl mRNA by inhibiting expression of c-Myc through ROS production. BPF also accelerated protein degradation of BCR-ABL through ROS production. Furthermore, BPF down-regulated the expression of not only BCR-ABL but also T315I-mutated BCR-ABL in ROS-dependent manner. As a result, BPF effectively induced apoptosis in transformed Ba/F3 cells expressing both BCR-ABL and T315I-mutated BCR-ABL. Collectively, these results indicate the potential of BPF as an effective leukemia drug that overcomes resistance to BCR-ABL inhibitors.

  • Novel Mechanism by a Bis-Pyridinium Fullerene Derivative to Induce Apoptosis by Enhancing the MEK-ERK Pathway in a Reactive Oxygen Species-Independent Manner in BCR-ABL-Positive Chronic Myeloid Leukemia-Derived K562 Cells.

    Sumi K, Tago K, Nakazawa Y, Takahashi K, Ohe T, Mashino T, Funakoshi-Tago M.

    Int J Mol Sci. 23 ( (2) ) 749 2022.01

    Research paper (scientific journal), Last author, Corresponding author, Accepted

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Papers, etc., Registered in KOARA 【 Display / hide 】

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Reviews, Commentaries, etc. 【 Display / hide 】

  • 炎症メディエーターと細胞 IL-1.

    笠原 忠、多胡めぐみ.

    炎症・再生医学事典(松島綱治、西脇徹編) (朝倉書店)  0   52-54 2009.04

    Article, review, commentary, editorial, etc. (scientific journal), Joint Work

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Presentations 【 Display / hide 】

  • Anti-cataract effect of coffee intake on selenite-induced cataract in rat

    TAGO Megumi

    日本薬学会第136年会（横浜）, 

    2016.03
    , 

    Poster presentation

  • Inhibitory effect of ParvifloronE on TNFa signaling pathway

    TAGO Megumi

    日本薬学会第136年会（横浜）, 

    2016.03
    , 

    Poster presentation

  • Anti-inflammatory activity of Coffee extract

    TAGO Megumi

    日本薬学会第136年会（横浜）, 

    2016.03
    , 

    Poster presentation

  • The role of DDX5 in JAK2 V617F mutant – induced transformation.

    TAGO Megumi

    日本薬学会第136年会（横浜）, 

    2016.03
    , 

    Poster presentation

  • Mechanism of NPM-ALK positive cells apoptosis induced by crizotinib

    TAGO Megumi

    日本薬学会第136年会（横浜）, 

    2016.03
    , 

    Poster presentation

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

  • Elucidation of pathogenesis of anaplastic large cell lymphoma via STAT3 target genes

    2023.04
    -
    2026.03

    基盤研究(C), Principal investigator

  • エリスロポエチン受容体結合分子を介した慢性骨髄増殖性腫瘍の発症機序の解明

    2020.04
    -
    2023.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator

  • エリスロポエチン受容体のリン酸化を介した慢性骨髄増殖性腫瘍の発症機序の解明

    2017.04
    -
    2020.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator

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Awards 【 Display / hide 】

  • 柿内三郎記念奨励研究賞第11回（2014年）

    多胡　めぐみ, 2014.10, 日本生化学会, 「定量的リン酸化プロテオミクスによる慢性骨髄増殖性腫瘍の発症機構の解析」

    Type of Award： Award from Japanese society, conference, symposium, etc.

  • 第11回(2014年）柿内三郎記念奨励研究賞

    多胡　めぐみ, 2014.10, 日本生化学会, 定量的リン酸化プロテオミクスによる慢性骨髄増殖性腫瘍の発症機構の解析

  • 平成22年度関東支部奨励賞

    Tago M., 2012.10, 日本薬学会, JAK2 変異体のシグナル伝達解析による真性赤血球増加症発症機構の解明.

  • FEBS Letters Young Group Leader Award 2011

    Tago M., 2012.09, FEBS Letters, FEBS Letters Young Group Leader Award 2012.

  • 2012 FEBS Letters Young Group Leader Award

    TAGO MEGUMI, 2012.09, FEBS, Aurora kinase A critically contributes to the resistance to anti-cancer drug cisplatin in JAK2 V617F mutant-induced transformed cells

    Type of Award： International academic award (Japan or overseas)

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Courses Taught 【 Display / hide 】

  • TOXICOLOGICAL SCIENCES

    2024

  • STUDY OF MAJOR FIELD: (HYGIENIC CHEMISTRY)

    2024

  • SEMINAR: (HYGIENIC CHEMISTRY)

    2024

  • RESEARCH FOR BACHELOR'S THESIS 1

    2024

  • PUBLIC HEALTH

    2024

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Memberships in Academic Societies 【 Display / hide 】

  • 日本薬学会、日本生化学会、日本分子生物学会

    　
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Committee Experiences 【 Display / hide 】

  • 2012.04
    -
    2014.03

    トピックス小委員, 日本薬学会

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