Tago, Megumi

写真a

Affiliation

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

Position

Professor

E-mail Address

E-mail address

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

Academic Background 【 Display / hide

  • 1998.03

    共立薬科大学, 薬学部, 薬学科

    JAPAN, 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

    JAPAN, Graduate School, Completed, Doctoral course

Academic Degrees 【 Display / hide

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

 

Research Areas 【 Display / hide

  • Biological pharmacy (Biological System Pharmaceutical Science)

Research Keywords 【 Display / hide

  • JAK2、STAT、erythropoietin、NF-kappaB

Research Themes 【 Display / hide

  • Analysis of cytokine signaling pathway, 

    2006
    -
    Present

 

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

Papers 【 Display / hide

  • 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

    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.

  • K15 promoter-driven enforced expression of NKIRAS exhibits tumor suppressive activity against the development of DMBA/TPA-induced skin tumors

    Tago K., Ohta S., Aoki-Ohmura C., Funakoshi-Tago M., Sashikawa M., Matsui T., Miyamoto Y., Wada T., Oshio T., Komine M., Matsugi J., Furukawa Y., Ohtsuki M., Yamauchi J., Yanagisawa K.

    Scientific Reports (Scientific Reports)  11 ( 1 )  2021.12

     View Summary

    NKIRAS1 and NKIRAS2 (also called as κB-Ras) were identified as members of the atypical RAS family that suppress the transcription factor NF-κB. However, their function in carcinogenesis is still controversial. To clarify how NKIRAS acts on cellular transformation, we generated transgenic mice in which NKIRAS2 was forcibly expressed using a cytokeratin 15 (K15) promoter, which is mainly activated in follicle bulge cells. The ectopic expression of NKIRAS2 was mainly detected in follicle bulges of transgenic mice with NKIRAS2 but not in wild type mice. K15 promoter-driven expression of NKIRAS2 failed to affect the development of epidermis, which was evaluated using the expression of K10, K14, K15 and filaggrin. However, K15 promoter-driven expression of NKIRAS2 effectively suppressed the development of skin tumors induced by treatment with 7,12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol 13-acetate (TPA). This observation suggested that NKIRAS seemed to function as a tumor suppressor in follicle bulges. However, in the case of oncogenic HRAS-driven cellular transformation of murine fibroblasts, knockdown of NKIRAS2 expression drastically suppressed HRAS-mutant-provoked cellular transformation, suggesting that NKIRAS2 was required for the cellular transformation of murine fibroblasts. Furthermore, moderate enforced expression of NKIRAS2 augmented oncogenic HRAS-provoked cellular transformation, whereas an excess NKIRAS2 expression converted its functional role into a tumor suppressive phenotype, suggesting that NKIRAS seemed to exhibit a biphasic bell-shaped enhancing effect on HRAS-mutant-provoked oncogenic activity. Taken together, the functional role of NKIRAS in carcinogenesis is most likely determined by not only cellular context but also its expression level.

  • Capsaicin attenuates TGFβ2-induced epithelial-mesenchymal-transition in lens epithelial cells in vivo and in vitro

    Sugiyama Y., Nakazawa Y., Sakagami T., Kawata S., Nagai N., Yamamoto N., Funakoshi-Tago M., Tamura H.

    Experimental Eye Research (Experimental Eye Research)  213 2021.12

    ISSN  00144835

     View Summary

    Posterior capsule opacification (PCO), the most common complication of cataract surgery occurring in 20–50% of patients after 2–5 years of cataract surgery, is a major problem in the aging society. The epithelial-mesenchymal transition (EMT) of lens epithelial cells after cataract surgery has been proposed as a major cause of PCO. Capsaicin, widely used as a food additive and analgesic agent, is a major pungent ingredient in red pepper. Although the effect of capsaicin on EMT has been reported in cancer cells, the biological reaction of capsaicin was unique in each cell type, and there have been no reports describing its effects on EMT earlier. In this study, we demonstrated that treatment with capsaicin inhibited TGFβ2-induced EMT in vitro lens epithelial cells and ex vivo explant lens epithelial cells. Furthermore, eye drops of capsaicin inhibited the PCO model mice in vivo. Finally, we showed that capsaicin inhibited non-canonically induced Smad2/3 activation via suppression of EGFR activation and ERK phosphorylation. Our findings indicate that capsaicin and its derivatives are good candidate compounds for preventing PCO after cataract surgery.

  • The indole-hydantoin derivative exhibits anti-inflammatory activity by preventing the transactivation of NF-κB through the inhibition of NF-κB p65 phosphorylation at Ser276

    Lin X., Tago K., Okazaki N., So T., Takahashi K., Mashino T., Tamura H., Funakoshi-Tago M.

    International Immunopharmacology (International Immunopharmacology)  100 2021.11

    ISSN  15675769

     View Summary

    Indole- and hydantoin-based derivatives both exhibit anti-inflammatory activity, suggesting that the structures of indole and hydantoin are functional for this activity. In the present study, we synthesized two types of indole-hydantoin derivatives, IH-1 (5-(1H-indole-3-ylmethylene) imidazolidine-2,4-dione) and IH-2 (5-(1H-indole-3-ylmethyl) imidazolidine-2,4-dione) and examined their effects on LPS-induced inflammatory responses in murine macrophage-like RAW264.7 cells. LPS-induced inflammatory responses were not affected by indole, hydantoin, or IH-2. In contrast, IH-1 significantly inhibited the LPS-induced production of nitric oxide (NO) and secretion of CCL2 and CXCL1 by suppressing the mRNA expression of inducible NO synthase (iNOS), CCL2, and CXCL1. IH-1 markedly inhibited the LPS-induced activation of NF-κB without affecting the degradation of IκBα or nuclear translocation of NF-κB. IH-1 markedly attenuated the transcriptional activity of NF-κB by suppressing the LPS-induced phosphorylation of the NF-κB p65 subunit at Ser276. Furthermore, IH-1 prevented the LPS-induced interaction of NF-κB p65 subunit with a transcriptional coactivator, cAMP response element-binding protein (CBP). Collectively, these results revealed the potential of the novel indole-hydantoin derivative, IH-1 as an anti-inflammatory drug.

  • Oral consumption of α-glucosyl-hesperidin could prevent lens hardening, which causes presbyopia

    Nakazawa Y., Aoki M., Doki Y., Morishita N., Endo S., Nagai N., Funakoshi-Tago M., Tamura H.

    Biochemistry and Biophysics Reports (Biochemistry and Biophysics Reports)  25 2021.03

    Research paper (scientific journal), Joint Work, Accepted

     View Summary

    © 2020 The Authors Presbyopia is one of the most well-known diseases of the eye, predominantly affecting the adult population after 50 years’. Due to hardening of the lens and failure of accommodative change, patients lose the ability to focus on near objects. This eye symptom is reported to be an early symptom of age-related nuclear cataract, and we have previously reported that hesperetin treatment could delay the onset of nuclear cataractogenesis induced by sodium selenite. In this study, we examined whether oral intake of α-glucosyl-hesperidin (G-Hsd), which has greater water solubility than hesperetin, could delay the onset of presbyopia. G-Hsd treatment protected lens elasticity, upregulated the mRNA expression of anti-oxidative enzymes like glutathione reductase and thioredoxin reductase 1 in the plasma and lens, and prevented premature cataract symptoms in selenite-induced cataract rat lens. Thus, the anti-presbyopic effects of G-Hsd were attributed, at least in part, to its antioxidant effects. G-Hsd represents the first oral treatment agent with anti-presbyopia and/or anti-cataract properties.

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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

    Introduction and explanation (scientific journal), Joint Work

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 (general)

  • Inhibitory effect of ParvifloronE on TNFa signaling pathway

    TAGO Megumi

    日本薬学会第136年会(横浜), 2016.03, Poster (general)

  • Anti-inflammatory activity of Coffee extract

    TAGO Megumi

    日本薬学会第136年会(横浜), 2016.03, Poster (general)

  • 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 (general)

  • 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 (general)

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

  • 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, 多胡 めぐみ, 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, 多胡 めぐみ, Grant-in-Aid for Scientific Research (C), Principal Investigator

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: Awards of National Conference, Council and Symposium

  • 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 Awards

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Courses Taught 【 Display / hide

  • TOXICOLOGICAL SCIENCES

    2021

  • STUDY OF MAJOR FIELD: (HYGIENIC CHEMISTRY)

    2021

  • SEMINAR: (HYGIENIC CHEMISTRY)

    2021

  • RESEARCH FOR BACHELOR'S THESIS 1

    2021

  • PUBLIC HEALTH

    2021

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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

     

Committee Experiences 【 Display / hide

  • 2012.04
    -
    2014.03

    トピックス小委員, 日本薬学会