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The investigation of respiratory diseases and development of novel therapeutics using up-to-date molecular and cellular techniques

Research Project

Project/Area Number 16H02653
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionThe University of Tokyo

Principal Investigator

NAGASE TAKAHIDE  東京大学, 医学部附属病院, 教授 (40208004)

Project Period (FY) 2016-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥46,280,000 (Direct Cost: ¥35,600,000、Indirect Cost: ¥10,680,000)
Fiscal Year 2020: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Fiscal Year 2019: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Fiscal Year 2018: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Fiscal Year 2017: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Fiscal Year 2016: ¥12,090,000 (Direct Cost: ¥9,300,000、Indirect Cost: ¥2,790,000)
Keywords呼吸器内科学 / 呼吸器内科
Outline of Final Research Achievements

In respiratory diseases, there are several disorders to which very few pharmaceutical agents are currently effective. These disorders include ARDS, IPF, COPD and lung cancer. Recently, new research tools such as genetically-engineered mice have been widely used to study molecular mechanisms underlying human disorders. The purpose of this study is to investigate mechanism of respiratory diseases and develop novel therapeutics using these up-to-date cellular and molecular techniques including genetically-engineered mice. Our observations suggest that this strategy might provide a novel therapeutic approach to respiratory disorders such as ARDS, IPF and COPD and lung cancer.

Academic Significance and Societal Importance of the Research Achievements

本研究では、発生工学的手法を応用し、疾患発症機序を明らかにし治療標的を探索した。難治性呼吸器系疾患に対する治療薬剤の開発は目下、困難を極めている。最新アプローチを駆使した本プロジェクトは、文字通り「ベンチからベッドへ」という橋渡し的役割を果たすものであり、その成果は、薬剤開発のプロセスを短縮し、実用化に大きく寄与することが予想される。また、難治性呼吸器系疾患に対する治療薬の開発は、社会医学的にも医療福祉・医療経済的にも莫大な貢献をなすことが予想される。

Report

(6 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (33 results)

All 2020 2019 2018 2017 2016

All Journal Article (29 results) (of which Int'l Joint Research: 10 results,  Peer Reviewed: 29 results,  Open Access: 18 results,  Acknowledgement Compliant: 6 results) Presentation (4 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results)

  • [Journal Article] FOXL1 Regulates Lung Fibroblast Function via Multiple Mechanisms2020

    • Author(s)
      Miyashita Naoya、Horie Masafumi、Suzuki Hiroshi I.、Saito Minako、Mikami Yu、Okuda Kenichi、Boucher Richard C.、Suzukawa Maho、Hebisawa Akira、Saito Akira、Nagase Takahide
    • Journal Title

      American Journal of Respiratory Cell and Molecular Biology

      Volume: 63 Issue: 6 Pages: 831-842

    • DOI

      10.1165/rcmb.2019-0396oc

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Secretory Cells Dominate Airway CFTR Expression and Function in Human Airway Superficial Epithelia2020

    • Author(s)
      Okuda K, , Nagase T, Boucher RC. et al
    • Journal Title

      American Journal of Respiratory and Critical Care Medicine

      Volume: - Issue: 10 Pages: 1275-1289

    • DOI

      10.1164/rccm.202008-3198oc

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Dual EGFR and ABL Tyrosine Kinase Inhibitor Treatment in a Patient with Concomitant EGFR-Mutated Lung Adenocarcinoma and BCR-ABL1-Positive CML2020

    • Author(s)
      Kousuke Watanabe, Hidenori Kage, Saki Nagoshi, Kazuhiro Toyama, Yoshiyuki Ohno, Aya Shinozaki-Ushiku, Kumi Nakazaki, Hiroshi Suzuki, Mineo Kurokawa, Takahide Nagase
    • Journal Title

      Case Rep Oncol Med

      Volume: 2020 Pages: 1-6

    • DOI

      10.1155/2020/4201727

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Active mTOR in Lung Epithelium Promotes Epithelial-Mesenchymal Transition and Enhances Lung Fibrosis2020

    • Author(s)
      Saito M, Mitani A, Ishimori T, Miyashita N, Isago H, Mikami Y, Noguchi S, Tarui M, Nagase T.
    • Journal Title

      Am J Respir Cell Mol Biol

      Volume: - Issue: 6 Pages: 699-708

    • DOI

      10.1165/rcmb.2019-0255oc

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhaled corticosteroid withdrawal may improve outcomes in elderly patients with COPD exacerbation: a nationwide database study2020

    • Author(s)
      Jo Taisuke、Yasunaga Hideo、Yamauchi Yasuhiro、Mitani Akihisa、Hiraishi Yoshihisa、Hasegawa Wakae、Sakamoto Yukiyo、Matsui Hiroki、Fushimi Kiyohide、Nagase Takahide
    • Journal Title

      ERJ Open Research

      Volume: 6 Issue: 1 Pages: 00246-2019

    • DOI

      10.1183/23120541.00246-2019

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epithelial Expression of YAP and TAZ Is Sequentially Required in Lung Development2020

    • Author(s)
      Isago Hideaki、Mitani Akihisa、Mikami Yu、Horie Masafumi、Urushiyama Hirokazu、Hamamoto Ryuji、Terasaki Yasuhiro、Nagase Takahide
    • Journal Title

      American Journal of Respiratory Cell and Molecular Biology

      Volume: 62 Issue: 2 Pages: 256-266

    • DOI

      10.1165/rcmb.2019-0218oc

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Integrin α11 in non-small cell lung cancer is associated with tumor progression and postoperative recurrence.2020

    • Author(s)
      Ando T, Kage H, Matsumoto Y, Zokumasu K, Yotsumoto T, Maemura K, Amano Y, Watanabe K, Nakajima J, Nagase T, Takai D.
    • Journal Title

      Cancer Sci

      Volume: 111 Issue: 1 Pages: 200-208

    • DOI

      10.1111/cas.14257

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Naftopidil reduced the proliferation of lung fibroblasts and bleomycin-induced lung fibrosis in mice.2019

    • Author(s)
      Urushiyama H, Terasaki Y, Nagasaka S, Kokuho N, Endo Y, Terasaki M, Kunugi S, Makita K, Isago H, Hosoki K, Souma K, Ishii T, Matsuzaki H, Hiraishi Y, Mikami Y, Noguchi S, Tamiya H, Mitani A, Yamauchi Y, Shimizu A, Nagase T.
    • Journal Title

      J Cell Mol Med.

      Volume: 3 Issue: 5 Pages: 1-9

    • DOI

      10.1111/jcmm.14255

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Activation through toll-like receptor 2 on group 2 innate lymphoid cells can induce asthmatic characteristics.2019

    • Author(s)
      Ishii T, Muroi M, Horiguchi K, Tanamoto KI, Nagase T, Yamashita N.
    • Journal Title

      Clin Exp Allergy.

      Volume: 49 Issue: 12 Pages: 1624-1632

    • DOI

      10.1111/cea.13490

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reference value for expiratory time constant calculated from the maximal expiratory flow-volume curve.2019

    • Author(s)
      Ikeda T, Yamauchi Y, Uchida K, Oba K, Nagase T, Yamada Y.
    • Journal Title

      BMC Pulm Med.

      Volume: 19 Issue: 1 Pages: 208-208

    • DOI

      10.1186/s12890-019-0976-6

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Small lung tumor biopsy samples are feasible for high quality targeted next generation sequencing2019

    • Author(s)
      Kage Hidenori、Kohsaka Shinji、Shinozaki‐Ushiku Aya、Hiraishi Yoshihisa、Sato Jiro、Nagayama Kazuhiro、Ushiku Tetsuo、Takai Daiya、Nakajima Jun、Miyagawa Kiyoshi、Aburatani Hiroyuki、Mano Hiroyuki、Nagase Takahide
    • Journal Title

      Cancer Science

      Volume: 110 Issue: 8 Pages: 2652-2657

    • DOI

      10.1111/cas.14112

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Localization of Secretory Mucins MUC5AC and MUC5B in Normal/Healthy Human Airways.2019

    • Author(s)
      Okuda K, Chen G, Subramani DB, Wolf M, Gilmore RC, Kato T, Radicioni G, Kesimer M, Chua M, Dang H, Livraghi-Butrico A, Ehre C, Doerschuk CM, Randell SH, Matsui H, Nagase T, O'Neal WK, Boucher RC.
    • Journal Title

      Am J Respir Crit Care Med

      Volume: 199 Issue: 6 Pages: 715-727

    • DOI

      10.1164/rccm.201804-0734oc

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] CISH is a negative regulator of IL-13-induced CCL26 production in lung fibroblasts2019

    • Author(s)
      Takeshima Hideyuki、Horie Masafumi、Mikami Yu、Makita Kosuke、Miyashita Naoya、Matsuzaki Hirotaka、Noguchi Satoshi、Urushiyama Hirokazu、Hiraishi Yoshihisa、Mitani Akihisa、Borok Zea、Nagase Takahide、Yamauchi Yasuhiro
    • Journal Title

      Allergology International

      Volume: 68 Issue: 1 Pages: 101-109

    • DOI

      10.1016/j.alit.2018.08.005

    • NAID

      130007557853

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Early stage non-small cell lung cancer patients need brain imaging regardless of symptoms.2018

    • Author(s)
      Ando T, Kage H, Saito M, Amano Y, Goto Y, Nakajima J, Nagase T.
    • Journal Title

      Int J Clin Oncol

      Volume: 23 Issue: 4 Pages: 641-646

    • DOI

      10.1007/s10147-018-1254-y

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mean platelet volume and lymphocyte-to-monocyte ratio are associated with shorter progression-free survival in EGFR-mutant lung adenocarcinoma treated by EGFR tyrosine kinase inhibitor.2018

    • Author(s)
      Watanabe K, Yasumoto A, Amano Y, Kage H, Goto Y, Yatomi Y, Takai D, Nagase T.
    • Journal Title

      PLoS One.

      Volume: - Issue: 9 Pages: e0203625-e0203625

    • DOI

      10.1371/journal.pone.0203625

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] An Integrative Analysis of Transcriptome and Epigenome Features of ASCL1-Positive Lung Adenocarcinomas.2018

    • Author(s)
      Miyashita N, Horie M, Suzuki HI, Yoshihara M, Djureinovic D, Persson J, Brunnstrom H, Lindskog C, Elfving H, Micke P, Saito A, Nagase T.
    • Journal Title

      J Thorac Oncol

      Volume: 13(11) Issue: 11 Pages: 1676-1691

    • DOI

      10.1016/j.jtho.2018.07.096

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Altered editing level of microRNAs is a potential biomarker in lung adenocarcinoma.2018

    • Author(s)
      Maemura K, Watanabe K, Ando T, Hiyama N, Sakatani T, Amano Y, Kage H, Nakajima J, Yatomi Y, Nagase T, Takai D.
    • Journal Title

      Cancer Sci

      Volume: 109 Issue: 10 Pages: 3326-3335

    • DOI

      10.1111/cas.13742

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An integrative transcriptome analysis reveals a functional role for thyroid transcription factor-1 in small cell lung cancer.2018

    • Author(s)
      Horie M, Miyashita N, Mattsson JSM, Mikami Y, Sandelin M, Brunnstrom H, Micke P, Nagase T, Saito A.
    • Journal Title

      J Pathol

      Volume: 246(2) Issue: 2 Pages: 154-165

    • DOI

      10.1002/path.5109

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] TBX4 is involved in the super-enhancer-driven transcriptional programs underlying features specific to lung fibroblasts.2018

    • Author(s)
      Horie M, Miyashita N, Mikami Y, Noguchi S, Yamauchi Y, Suzukawa M, Fukami T, Ohta K, Asano Y, Sato S, Yamaguchi Y, Ohshima M, Suzuki HI, Saito A, Nagase T.
    • Journal Title

      Am J Physiol Lung Cell Mol Physiol.

      Volume: 314 Issue: 1 Pages: L177-L191

    • DOI

      10.1152/ajplung.00193.2017

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Orchestrating Role of Apoptosis Inhibitor of Macrophage in the Resolution of Acute Lung Injury.2017

    • Author(s)
      Kimura H, Suzuki M, Konno S, Shindou H, Shimizu T, Nagase T, Miyazaki T, Nishimura M.
    • Journal Title

      J Immunol.

      Volume: 199 Issue: 11 Pages: 3870-3882

    • DOI

      10.4049/jimmunol.1601798

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association between dementia and discharge status in patients hospitalized with pneumonia.2017

    • Author(s)
      Jo T, Yasunaga H, Sasabuchi Y, Michihata N, Morita K, Yamauchi Y, Hasegawa W, Takeshima H, Sakamoto Y, Matsui H, Fushimi K, Nagase T.
    • Journal Title

      BMC Pulm Med

      Volume: 128 Issue: 1 Pages: 128-128

    • DOI

      10.1186/s12890-017-0473-8

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Integrative CAGE and DNA Methylation Profiling Identify Epigenetically Regulated Genes in NSCLC2017

    • Author(s)
      Horie M, Kaczkowski B, Ohshima M, Matsuzaki H, Noguchi S, Mikami Y, Lizio M, Itoh M, Kawaji H, Lassmann T, Carninci P, Hayashizaki Y, Forrest ARR, Takai D, Yamaguchi Y, Micke P, Saito A, Nagase T.
    • Journal Title

      Mol Cancer Res.

      Volume: 15 Issue: 10 Pages: 1354-1365

    • DOI

      10.1158/1541-7786.mcr-17-0191

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] IFN Regulatory Factor 3 Potentiates Emphysematous Aggravation by Lipopolysaccharide.2017

    • Author(s)
      Ishii T, Hosoki K, Nikura Y, Yamashita N, Nagase T, Yamashita N.
    • Journal Title

      J Immunol.

      Volume: 198 Issue: 9 Pages: 3637-3649

    • DOI

      10.4049/jimmunol.1601069

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] TAZ contributes to pulmonary fibrosis by activating profibrotic functions of lung fibroblasts.2017

    • Author(s)
      Noguchi S, Saito A, Mikami Y, Urushiyama H, Horie M, Matsuzaki H, Takeshima H, Makita K, Miyashita N, Mitani A, Jo T, Yamauchi Y, Terasaki Y, Nagase T.
    • Journal Title

      Sci Rep

      Volume: 7 Issue: 1 Pages: 42595-42595

    • DOI

      10.1038/srep42595

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Development of an In Vitro Assay to Evaluate Contractile Function of Mesenchymal Cells that Underwent Epithelial-Mesenchymal Transition.2016

    • Author(s)
      Mikami Y, Matsuzaki H, Takeshima H, Makita K, Yamauchi Y, Nagase T.
    • Journal Title

      J Vis Exp

      Volume: 112 Issue: 112

    • DOI

      10.3791/53974

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] YAP and TAZ modulate cell phenotype in a subset of small cell lung cancer.2016

    • Author(s)
      Horie M, Saito A, Ohshima M, Suzuki HI, Nagase T.
    • Journal Title

      Cancer Sci

      Volume: 107 Issue: 12 Pages: 1755-1766

    • DOI

      10.1111/cas.13078

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Transcriptome analysis of periodontitis-associated fibroblasts by CAGE sequencing identified DLX5 and RUNX2 long variant as novel regulators involved in periodontitis.2016

    • Author(s)
      Horie M, Yamaguchi Y, Saito A, Nagase T, Lizio M, Itoh M, Kawaji H, Lassmann T, Carninci P, Forrest AR, Hayashizaki Y, Suzutani T, Kappert K, Micke P, Ohshima M.
    • Journal Title

      Sci Rep

      Volume: 6 Issue: 1

    • DOI

      10.1038/srep33666

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Effect of outpatient therapy with inhaled corticosteroids on decreasing in-hospital mortality from pneumonia in patients with COPD.2016

    • Author(s)
      Yamauchi Y, Yasunaga H, Hasegawa W, Sakamoto Y, Takeshima H, Jo T, Matsui H, Fushimi K, Nagase T
    • Journal Title

      Int J Chron Obstruct Pulmon Dis

      Volume: 11 Pages: 1403-1411

    • DOI

      10.2147/copd.s107985

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Mortality associated with bone fractures in COPD patients2016

    • Author(s)
      Yamauchi Y, Yasunaga H, Sakamoto Y, Hasegawa W, Takeshima H, Urushiyama H, Jo T, Matsui H, Fushimi K, Nagase T.
    • Journal Title

      Int J Chron Obstruct Pulmon Dis

      Volume: 11 Pages: 2335-2340

    • DOI

      10.2147/copd.s112142

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] レプチンによる肺線維芽細胞のサイトカイン産生増強作用とその機序の検討2020

    • Author(s)
      渡邊かおる、鈴川真穂、長瀬隆英 et. al.
    • Organizer
      日本呼吸器学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Effects of ASCL1 expression on cytokine/chemokine expression and tumorigenesis.2019

    • Author(s)
      Miyashita N, Horie M, Mikami Y, Urushiyama H, Fukuda K, Makita K, Matsuzaki H, Saito A, Nagase T.
    • Organizer
      日本呼吸器学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Respiratory research using cellular, molecular and physiologic approaches2017

    • Author(s)
      Nagase T
    • Organizer
      Asian Pacific Society of Respirology (APSR),2017, Sydney
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Recent progress in respiratory cells and molecular biology2016

    • Author(s)
      長瀬隆英
    • Organizer
      APSR 2016
    • Place of Presentation
      バンコク
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited

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Published: 2016-04-21   Modified: 2022-01-27  

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