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Molecular physiological studies of in vivo hypoxia niche: formation, sensing and adaptation

Planned Research

Project AreaOxygen biology: a new criterion for integrated understanding of life
Project/Area Number 26111004
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionKyoto University

Principal Investigator

Mori Yasuo  京都大学, 工学研究科, 教授 (80212265)

Co-Investigator(Kenkyū-buntansha) 矢部 大介  京都大学, 医学研究科, 特定准教授 (60378643)
長嶋 一昭  京都大学, 医学研究科, 講師 (40324628)
Research Collaborator NAGAMATSU go  
TAKUBO keiyo  
MORI masayuki  
KUROKAWA tatsuki  
SAKAGUCHI reiko  
Project Period (FY) 2014-07-10 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥112,840,000 (Direct Cost: ¥86,800,000、Indirect Cost: ¥26,040,000)
Fiscal Year 2018: ¥26,520,000 (Direct Cost: ¥20,400,000、Indirect Cost: ¥6,120,000)
Fiscal Year 2017: ¥26,520,000 (Direct Cost: ¥20,400,000、Indirect Cost: ¥6,120,000)
Fiscal Year 2016: ¥25,090,000 (Direct Cost: ¥19,300,000、Indirect Cost: ¥5,790,000)
Fiscal Year 2015: ¥21,320,000 (Direct Cost: ¥16,400,000、Indirect Cost: ¥4,920,000)
Fiscal Year 2014: ¥13,390,000 (Direct Cost: ¥10,300,000、Indirect Cost: ¥3,090,000)
Keywords酸素 / 活性酸素種 / 細胞シグナル / イメージング / 低酸素 / イオンチャネル / 酸素受容 / アストロサイト / 神経系 / ハイポキシア / チャネル / 酸素受容器 / TRPチャネル / カルシウム / 一酸化窒素 / 生理学 / 活性酸素
Outline of Final Research Achievements

In order to elucidate mechanisms underlying formation, sensing, adaptation, and their significance for physiological hypoxia environment in vivo, I investigated how acute hypoxia responses, which are distributed ubiquitously throughout the mammalian body, are integrated as neural outputs in the respiratory regulation. Also, in collaboration with other members of our innovative area, I developed new imaging techniques by combining our own probes for oxygen, ROS, and energy production with multiphoton imaging systems, and succeeded in quantifying their presence in vivo . Moreover, I addressed questions from biological perspectives how oxygen environment in vivo controls signaling cascades and gene transcription.

Academic Significance and Societal Importance of the Research Achievements

酸素センサー細胞・分子の同定を中心に、生体内低酸素環境の形成・感知・適応の基盤となる機構、及びその意義の理解を前進させることができた。また、酸素生物学分野は大きく変化、拡大しており、研究者間の相互連携が取りにくい分散的状況にあったが、本研究を含む領域の活動により、この解決に向けた大きな一歩を踏み出すことができた。本成果は異分野の世界的な統合・再構築は、日本の学術レベルと世界におけるプレゼンスの向上・強化に貢献した。さらに、基礎生物学、医科学、薬学、農学を含めた幅広い分野に関係し、臨床医学、医工学、食品・発酵化、環境科学やケミカルバイオロジーといった学際・応用分野の発展にも結び付いた。

Report

(6 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (40 results)

All 2019 2018 2017 2016 2015 2014 2013 Other

All Int'l Joint Research (8 results) Journal Article (31 results) (of which Int'l Joint Research: 14 results,  Peer Reviewed: 30 results,  Open Access: 17 results,  Acknowledgement Compliant: 11 results) Remarks (1 results)

  • [Int'l Joint Research] ハーバード大学/テキサス大学/ユタ大学(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] ヘブライ大学(イスラエル)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Sevilla大学(スペイン)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] トロント大学(カナダ)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] NIH(米国)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] NIH(米国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] ミュンヘン大学(ドイツ)

    • Related Report
      2015 Annual Research Report
  • [Int'l Joint Research] トロント大学(カナダ)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] TRPM7 channels mediate spontaneous Ca2+ fluctuations in growth plate chondrocytes that promote bone development.2019

    • Author(s)
      Qian N, Ichimura A, Takei D, Sakaguchi R, Kitani A, Nagaoka R, Tomizawa M, Miyazaki Y, Miyachi H, Numata T, Kakizawa S, Nishi M, Mori Y, Takeshima H.
    • Journal Title

      Science signaling

      Volume: 12 Issue: 576 Pages: 4847-4847

    • DOI

      10.1126/scisignal.aaw4847

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] TRPM2 mediates neutrophil killing of disseminated tumor cells.2018

    • Author(s)
      Gershkovitz M, Caspi Y, Fainsod-Levi T, Katz B, Michaeli J, Khawaled S, Lev S, Polyansky L, Shaul ME, Sionov RV, Cohen-Daniel L, Aqeilan RI, Shaul Y, Mori Y, Karni R, Fridlender ZG, Binshtok AM, Granot Z
    • Journal Title

      Cancer Res.

      Volume: 78 Issue: 10 Pages: 2680-2690

    • DOI

      10.1158/0008-5472.can-17-3614

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] TRPM2 Channel Aggravates CNS Inflammation and Cognitive Impairment via Activation of Microglia in Chronic Cerebral Hypoperfusion2018

    • Author(s)
      Miyanohara Jun、Kakae Masashi、Nagayasu Kazuki、Nakagawa Takayuki、Mori Yasuo、Arai Ken、Shirakawa Hisashi、Kaneko Shuji
    • Journal Title

      The Journal of Neuroscience

      Volume: 38 Issue: 14 Pages: 3520-3533

    • DOI

      10.1523/jneurosci.2451-17.2018

    • NAID

      120006630983

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Role of transient receptor potential melastatin 2 in surgical inflammation and dysmotility in a mouse model of post-operative ileus2018

    • Author(s)
      Matsumoto Kenjiro、Kawanaka Hiroki、Hori Masatoshi、Kusamori Kosuke、Utsumi Daichi、Tsukahara Takuya、Amagase Kikuko、Horie Syunji、Yamamoto Akira、Ozaki Hiroshi、Mori Yasuo、Kato Shinichi
    • Journal Title

      American Journal of Physiology-Gastrointestinal and Liver Physiology

      Volume: 印刷中 Issue: 1 Pages: G104-G116

    • DOI

      10.1152/ajpgi.00305.2017

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cancer cells co-opt the neuronal redox-sensing channel TRPA1 to promote oxidative-stress tolerance.2018

    • Author(s)
      Takahashi N, Chen HY, Harris IS, Stover DG, Selfors LM, Bronson RT, Deraedt T, Cichowski K, Welm AL, Mori Y, Mills GB, Brugge JS
    • Journal Title

      Cancer Cell

      Volume: 33 Issue: 6 Pages: 985-1003

    • DOI

      10.1016/j.ccell.2018.05.001

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] TRPM2 Exacerbates Central Nervous System Inflammation in Experimental Autoimmune Encephalomyelitis by Increasing Production of CXCL2 Chemokines.2018

    • Author(s)
      Tsutsui M, Hirase R, Miyamura S, Nagayasu K, Nakagawa T, Mori Y, Shirakawa H, Kaneko S.
    • Journal Title

      J Neurosci.

      Volume: 38 Issue: 39 Pages: 8484-8495

    • DOI

      10.1523/jneurosci.2203-17.2018

    • NAID

      120006630992

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 総論 新たな酸素生物学へ2018

    • Author(s)
      森泰生
    • Journal Title

      細胞 (特集:酸素生物学 Oxygen Biology、森泰生 編)

      Volume: 50 Pages: 170-171

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Radiation inhibits salivary gland function by promoting STIM1 cleavage by caspase-3 and loss of SOCE through a TRPM2-dependent pathway.2017

    • Author(s)
      Liu X, Gong B, de Souza LB, Ong HL, Subedi KP, Cheng KT, Swaim W, Zheng C, Mori Y, Ambudkar IS.
    • Journal Title

      Science Signal.

      Volume: 10 Issue: 482 Pages: 482-482

    • DOI

      10.1126/scisignal.aal4064

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Integrative Approach with Electrophysiological and Theoretical Methods Reveals a New Role of S4 Positively Charged Residues in PKD2L1 Channel Voltage-Sensing2017

    • Author(s)
      Numata Tomohiro、Tsumoto Kunichika、Yamada Kazunori、Kurokawa Tatsuki、Hirose Shinichi、Nomura Hideki、Kawano Mitsuhiro、Kurachi Yoshihisa、Inoue Ryuji、Mori Yasuo
    • Journal Title

      Sci. Rep.

      Volume: 7 Issue: 1 Pages: 9760-9760

    • DOI

      10.1038/s41598-017-10357-3

    • NAID

      120006364088

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] TRPC3-Nox2 complex mediates doxorubicin-induced myocardial atrophy2017

    • Author(s)
      Shimauchi Tsukasa、Numaga-Tomita Takuro、Ito Tomoya、Nishimura Akiyuki、Matsukane Ryosuke、Oda Sayaka、Hoka Sumio、Ide Tomomi、Koitabashi Norimichi、Uchida Koji、Sumimoto Hideki、Mori Yasuo、Nishida Motohiro
    • Journal Title

      The JCI insight

      Volume: 2 Issue: 15 Pages: 93358-93358

    • DOI

      10.1172/jci.insight.93358

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mast cell hyperactivity underpins the development of oxygen-induced retinopathy.2017

    • Author(s)
      Matsuda K, Okamoto N, Kondo M, Arkwright PD, Karasawa K, Ishizaka S, Yokota S, Matsuda A, Jung K, Oida K, Amagai Y, Jang H, Noda E, Kakinuma R, Yasui K, Kaku U, Mori Y, Onai N, Ohteki T, Tanaka A, Matsuda H
    • Journal Title

      J. Clin. Invest.

      Volume: 127 Issue: 11 Pages: 3987-4000

    • DOI

      10.1172/jci89893

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Distinct Mechanism of Cysteine Oxidation-Dependent Activation and Cold Sensitization of Human Transient Receptor Potential Ankyrin 1 Channel by High and Low Oxaliplatin2017

    • Author(s)
      Miyake Takahito、Nakamura Saki、Meng Zhao、Hamano Satoshi、Inoue Keisuke、Numata Tomohiro、Takahashi Nobuaki、Nagayasu Kazuki、Shirakawa Hisashi、Mori Yasuo、Nakagawa Takayuki、Kaneko Shuji
    • Journal Title

      Frontiers in Physiology

      Volume: 8 Pages: 878-878

    • DOI

      10.3389/fphys.2017.00878

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] TRP channels in oxygen physiology: distinctive functional properties and roles of TRPA1 in O<sub>2</sub> sensing2017

    • Author(s)
      MORI Yasuo、TAKAHASHI Nobuaki、KUROKAWA Tatsuki、KIYONAKA Shigeki
    • Journal Title

      Proceedings of the Japan Academy, Series B

      Volume: 93 Issue: 7 Pages: 464-482

    • DOI

      10.2183/pjab.93.028

    • NAID

      130005881887

    • ISSN
      0386-2208, 1349-2896
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hypoxia-induced sensitization of TRPA1 in painful dysesthesia evoked by transient hindlimb ischemia/reperfusion in mice2016

    • Author(s)
      So K, Tei Y, Zhao M, Miyake T, Hiyama H, Shirakawa H, Imai S, Mori Y, Nakagawa T, Matsubara K, Kaneko S
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 23261-23261

    • DOI

      10.1038/srep23261

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Cold sensitivity of TRPA1 is unveiled by the prolyl hydroxylation blockade-induced sensitization to ROS.2016

    • Author(s)
      Miyake T, Nakamura S, Zhao M, So K, Inoue K, Numata T, Takahashi N, Shirakawa H, Mori Y, Nakagawa T, Kaneko S
    • Journal Title

      Nature Communications

      Volume: 7 Issue: 1 Pages: 12840-12840

    • DOI

      10.1038/ncomms12840

    • NAID

      120005842688

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] TRPC3 positively regulates reactive oxygen species driving maladaptive cardiac remodeling.2016

    • Author(s)
      Kitajima N., Numaga-Tomita T., Watanabe M., Kuroda T., Nishimura A., Miyano K., Yasuda S., Kuwahara K., Sato Y., Ide T., Birnbaumer L., Sumimoto H., Mori Y. and Nishida M
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 37701-37701

    • DOI

      10.1038/srep37001

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] TRPC3-GEF-H1 axis mediates pressure overload-induced cardiac fibrosis.2016

    • Author(s)
      Numaga-Tomita T., Kitajima N., Kuroda T., Nishimura A., Miyano K., Yasuda S., Kuwahara K., Sato Y., Ide T., Birnbaumer L., Sumimoto H., Mori Y. and Nishida M.
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 39383-39383

    • DOI

      10.1038/srep39383

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Sensing of redox status by TRP channels.2016

    • Author(s)
      Ogawa N, Kurokawa T, Mori Y
    • Journal Title

      Cell Calcium

      Volume: 60 Issue: 2 Pages: 115-122

    • DOI

      10.1016/j.ceca.2016.02.009

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] TRPM2 channels in alveolar epithelial cells mediate bleomycin-induced lung inflammation2016

    • Author(s)
      Yonezawa R, Yamamoto S, Takenaka M, Kage Y, Negoro T, Toda T, Ohbayashi M, Numata T, Nakano Y, Yamamoto T, Mori Y, Ishii M, Shimizu S
    • Journal Title

      Free Radic Biol Med

      Volume: 90 Pages: 101-113

    • DOI

      10.1016/j.freeradbiomed.2015.11.021

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Functional and Structural Divergence in Human TRPV1 Channel Subunits by Oxidative Cysteine Modification2016

    • Author(s)
      Ogawa N, Kurokawa T, Fujiwara K, Polat OK, Badr H, Takahashi N, Mori Y
    • Journal Title

      J. Biol. Chem.

      Volume: 291 Issue: 8 Pages: 4197-4210

    • DOI

      10.1074/jbc.m115.700278

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Screening of Transient Receptor Potential Canonical Channel Activators Identifies Novel Neurotrophic Piperazine Compounds2016

    • Author(s)
      S. Sawamura, M. Hatano, Y. Takada, K. Hino, T. Kawamura, J. Tanikawa, H. Nakagawa, H. Hase, A. Nakao, M. Hirano, R. Rotrattanadumrong, S. Kiyonaka, M.X. Mori, M. Nishida, Y. Hu, R. Inoue, R. Nagata and Y. Mori
    • Journal Title

      Mol Pharmacol

      Volume: 89(3) Issue: 3 Pages: 348-363

    • DOI

      10.1124/mol.115.102863

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of a prostaglandin D2 metabolite as a neuritogenesis enhancer targeting the TRPV1 ion channel.2016

    • Author(s)
      Shibata T, Takahashi K, Matsubara Y, Inuzuka E, Nakashima F, Takahashi N, Kozai D, Mori Y, Uchida K
    • Journal Title

      Sci Rep.

      Volume: 6 Issue: 1 Pages: 21261-21261

    • DOI

      10.1038/srep21261

    • NAID

      120005820880

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Different Contribution of Redox-Sensitive Transient Receptor Potential Channels to Acetaminophen-Induced Death of Human Hepatoma Cell Line2016

    • Author(s)
      Badr H, Kozai D, Sakaguchi R, Numata T, Mori Y
    • Journal Title

      Front. Pharmacol.

      Volume: 7 Pages: 19-19

    • DOI

      10.3389/fphar.2016.00019

    • NAID

      120005848247

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Redox-sensitive transient receptor potential channels in oxygen sensing and adaptation.2016

    • Author(s)
      Mori Y, Takahashi N, Polat OK, Kuroakwa T, Takeda N, Inoue M
    • Journal Title

      Pflugers Arch. Eur. J. Physiol.

      Volume: 468 Issue: 1 Pages: 85-97

    • DOI

      10.1007/s00424-015-1716-2

    • NAID

      120005980858

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Validating subcellular thermal changes revealed by fluorescent thermosensors2015

    • Author(s)
      Kiyonaka S, Sakaguchi R, Hamachi I, Morii T, Yoshizaki T, Mori Y
    • Journal Title

      Nature Method.

      Volume: 12 Issue: 9 Pages: 801-802

    • DOI

      10.1038/nmeth.3548

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A potent and site-selective agonist of TRPA1.2015

    • Author(s)
      Takaya, J., Mio, K., Shiraishi, T., Kurokawa, T., Otsuka, S., Mori, Y., Uesugi, M.
    • Journal Title

      J. Am. Chem. Soc.

      Volume: 137 Issue: 50 Pages: 15859-15864

    • DOI

      10.1021/jacs.5b10162

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Transient receptor potential melastatin 2 protects mice against polymicrobial sepsis by enhancing bacterial clearance.2014

    • Author(s)
      Qian X, Numata T, Zhang K, Li C, Hou J, Mori Y & Fang X
    • Journal Title

      Anesthesiology

      Volume: 121 Issue: 2 Pages: 336-351

    • DOI

      10.1097/aln.0000000000000275

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] TRPV4 channel activity is modulated by direct interaction of the ankyrin domain to PI(4,5)P22014

    • Author(s)
      Nobuaki Takahashi, Sayaka Hamada-Nakahara, Yuzuru Itoh, Kazuhiro Takemura, Atsushi Shimada,Yoshifumi Ueda, Manabu Kitamata, Rei Matsuoka, Kyoko Hanawa-Suetsugu, Yosuke Senju, Masayuki X. Mori, Shigeki Kiyonaka, Daisuke Kohda, Akio Kitao, Yasuo Mori and Shiro Suetsugu
    • Journal Title

      Nature Communications

      Volume: 5 Issue: 1 Pages: 4994-4994

    • DOI

      10.1038/ncomms5994

    • NAID

      130005100825

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The O(2)-sensing TRPA1 channel illustrates the significance of vagal nerves in cardio-respiratory adaptation to hypoxia.2014

    • Author(s)
      Takahashi N, Mori Y
    • Journal Title

      Acta Physiol (Oxf)

      Volume: 210 Issue: 4 Pages: 705-707

    • DOI

      10.1111/apha.12251

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] BARP suppresses voltage-gated calcium channel activity and Ca2+-evoked exocytosis2014

    • Author(s)
      Beguin P, Nagashima K, Mahalakshmi RN, Vigot R, Matsunaga A, Miki T, Ng MY, Ng YJ, Lim CH, Tay HS, Hwang LA, Firsov D, Tang BL, Inagaki N, Mori Y, Seino S, Launey T, Hunziker W
    • Journal Title

      J Cell Biol

      Volume: 205 Issue: 2 Pages: 233-249

    • DOI

      10.1083/jcb.201304101

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Glucose-stimulated single pancreatic islets sustain increased cytosolic ATP levels during initial Ca2+ influx and subsequent Ca2+ oscillations2013

    • Author(s)
      Tanaka T, Nagashima K, Inagaki N, Kioka H, Takashima S, Fukuoka H, Noji H, Kakizuka A and Imamura H
    • Journal Title

      J Biol Chem

      Volume: 289 Issue: 4 Pages: 2205-2216

    • DOI

      10.1074/jbc.m113.499111

    • NAID

      120005689188

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Remarks] 【森研究室】京都大学大学院工学研究科 合成・生物化学専攻 分子生物化学分野 森研究室

    • URL

      http://www.sbchem.kyoto-u.ac.jp/mori-lab/

    • Related Report
      2014 Annual Research Report

URL: 

Published: 2014-11-20   Modified: 2022-02-28  

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