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Development of the Innovative Bio-imaging for Non-invasive and Spatio-temporal Monitoring of Molecular-targeted Drug

Research Project

Project/Area Number 15H05659
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Applied pharmacology
Research InstitutionHokkaido University

Principal Investigator

Haga Sanae  北海道大学, 保健科学研究院, 特任講師 (60706505)

Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥23,270,000 (Direct Cost: ¥17,900,000、Indirect Cost: ¥5,370,000)
Fiscal Year 2018: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
Keywords生体分子機能 / 光イメージング / 細胞死 / 創薬 / イメージング / プローブ / 生体分子 / 診断
Outline of Final Research Achievements

In the present study, we tried to do develop the newly bio-imaging probe, which based on the antibody and observed molecular function, and intracellular delivery system, and validate the functionality and availability of the probes. These probes were originally designed and developed by the opto-engineering techniques using luciferase and other light-sensitive molecules, which allowed us to observe and control the molecular functions non-invasively and continuously. By these newly developed tools, we spatio-temporally succeeded in visualization and evaluation of cell survival- and death-associated signals and to control cellular function.
These results will provide important perspectives on the potential pathological and therapeutic roles of molecular signals in cancer and other diseases and contribute to the development of more effective drugs in shorter periods.

Academic Significance and Societal Importance of the Research Achievements

薬剤の効果、毒性・副作用、体内動態などの解析には莫大な費用と時間、労力が支払われるが、実際に臨床研究に辿り着くものはごくわずかである。これらの課題に対して、本研で進めた光プローブの技術開発は、生体、細胞内の病態制御分子の動態をより迅速かつ理論的に、時空間的に確認することを可能にした。
本研究成果は、生物学的光イメージング診断・治療、薬剤評価、そして疾患研究のツールとして、臨床現場で広く応用可能な技術をもたらすと期待している。

Report

(5 results)
  • 2019 Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (33 results)

All 2019 2018 2017 2016 2015

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (27 results) (of which Int'l Joint Research: 3 results,  Invited: 4 results)

  • [Journal Article] Extracts of Bilberry ( Vaccinium myrtillus L.) Fruits Improve Liver Steatosis and Injury in Mice by Preventing Lipid Accumulation and Cell Death2019

    • Author(s)
      Sanae Haga, Yimin, Hikari Yamaki, Shigeki Jin, Tetsuya Sogon, Naoki Morita, Michitaka Ozaki.
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: 83 Issue: 11 Pages: 2110-2120

    • DOI

      10.1080/09168451.2019.1634514

    • NAID

      120006864495

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activation of caspase-3 during Chlamydia trachomatis-induced apoptosis at a late stage2019

    • Author(s)
      Matsuo Junji、Haga Sanae、Hashimoto Kent、Okubo Torahiko、Ozawa Takeaki、Ozaki Michitaka、Yamaguchi Hiroyuki
    • Journal Title

      Canadian Journal of Microbiology

      Volume: 65 Issue: 2 Pages: 135-143

    • DOI

      10.1139/cjm-2018-0408

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Photo-Activatable Akt Probe: A New Tool to Study the Akt-Dependent Physiopathology of Cancer Cells2018

    • Author(s)
      Haga Sanae、Ozawa Takeaki、Morita Naoki、Asano Mami、Jin Shigeki、Yimin、Ozaki Michitaka
    • Journal Title

      Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics

      Volume: 26 Issue: 3 Pages: 467-472

    • DOI

      10.3727/096504017x15040166233313

    • NAID

      120006473610

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Detection of necroptosis in ligand-mediated and hypoxia-induced injury of hepatocytes using a novel optic probe detecting receptor-interacting protein (RIP)1/RIP3 binding2018

    • Author(s)
      S. Haga, A. Kanno, T. Ozawa, N. Morita, M. Asano, M. Ozaki
    • Journal Title

      Oncology Research

      Volume: 26 Issue: 3 Pages: 503-513

    • DOI

      10.3727/096504017x15005102445191

    • NAID

      120006473611

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Relevance of FXR-p62/SQSTM1 pathway for survival and protection of mouse hepatocytes and liver, especially with steatosis.2017

    • Author(s)
      Sanae Haga, Yimin, Michitaka Ozaki.
    • Journal Title

      BMC Gastroenterology

      Volume: 17 Issue: 1 Pages: 9-9

    • DOI

      10.1186/s12876-016-0568-3

    • NAID

      120005981455

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Long-term ex vivo and in vivo monitoring of tumor progression by using dual luciferases.2016

    • Author(s)
      Naoki Morita, Sanae Haga, Yoshihiro Ohmiya, Michitaka Ozaki.
    • Journal Title

      Analytical Chemistry

      Volume: 497 Pages: 24-26

    • DOI

      10.1016/j.ab.2015.12.007

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Presentation] Palmitate induces release of pro-inflammatory cytokines prior to cell death in mouse AML12 hepatocytes.2019

    • Author(s)
      Mami Asano, Sanae Haga, Shiina Itashiki, Sae Kamada, Aya Mikami, Michitaka Ozaki.
    • Organizer
      CSH-Asia Liver, Biology, Diseases & Cancer,
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Fasリガンド/酸化ストレスによって引き起こされるプログラム細胞死の機序解析 Analysis of programmed cell death in hepatocytes induced by Fas ligand and oxidative stressw2019

    • Author(s)
      芳賀 早苗、森田 直樹、尾崎 倫孝
    • Organizer
      第92回日本生化学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 肝虚血・再灌流、酸化ストレスと細胞死(臓器傷害)とその制御 -マウス肝における虚血再灌流傷害進展の分子機構 -2019

    • Author(s)
      尾崎 倫孝、芳賀 早苗、森田 直樹、小澤 岳昌
    • Organizer
      第72回日本酸化ストレス学会学術集会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 脂肪肝における易傷害性メカニズム解析の基礎的研究2019

    • Author(s)
      芳賀 早苗、浅野 真未、森田 直樹、尾崎 倫孝
    • Organizer
      第26回肝細胞研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 細胞・臓器の病態生理の時空間イメージングと研究・臨床への応用- 外科医が望むもの、そして今していること -2018

    • Author(s)
      尾崎 倫孝、芳賀 早苗、森田 直樹、浜田 俊幸、小 澤岳昌
    • Organizer
      第16回医用分光学研究会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] マウス脂肪肝モデルをもちいたビルベリーの予防効果に関する検討2018

    • Author(s)
      芳賀 早苗、伊 敏、森田 直樹、浅野 真未、荘厳 哲哉、尾崎 倫孝
    • Organizer
      第39会日本肥満学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 光による細胞生存能(Akt/PKB分子)制御に関する研究2018

    • Author(s)
      芳賀 早苗、小澤 岳昌、森田 直樹、伊 敏、尾崎 倫孝
    • Organizer
      第91回日本生化学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Relevance of FXR-p62/SQSTM1 pathway for survival and protection of mouse hepatocytes and liver with steatosis.2018

    • Author(s)
      Michitaka Ozaki, Sanae Haga, Yimin.
    • Organizer
      IBD and Liver: East Meets West
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 発光プローブによるプログラム細胞死(アポトーシス、ネクロプトーシス)動的解析の試み2018

    • Author(s)
      芳賀 早苗、菅野 憲、小澤 岳昌、森田 直樹、浅野 真未、伊 敏、尾崎 倫孝
    • Organizer
      第27回日本Cell Death学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] レドックスが制御するネクローシス型細胞死(ネクロプトーシス)の光プローブによる動的解析2018

    • Author(s)
      芳賀 早苗、菅野 憲、小澤 岳昌、森田 直樹、浅野 真未、尾崎 倫孝
    • Organizer
      第25回肝細胞研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 光プローブをもちいたプログラム細胞死(アポトーシス、ネクロプトーシス)の動的解析2018

    • Author(s)
      尾崎 倫孝,芳賀 早苗
    • Organizer
      第22回日本がん分子標的治療学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] カスパーゼ3プローブ発現細胞を用いたクラミジア感染宿主細胞内のアポトーシス制御機構の探索2017

    • Author(s)
      松尾 淳司、芳賀 早苗、大久保 寅彦、中村 眞二、小澤 岳昌、尾崎 倫孝、山口 博之
    • Organizer
      ConBio2017
    • Related Report
      2017 Annual Research Report
  • [Presentation] ビルベリー抽出物の糖尿病性網膜症発症・進行予防効果に関する基礎的研究2017

    • Author(s)
      浅野 真未、芳賀 早苗、柴崎 彩、黒澤 和也、荘厳 哲哉、尾崎 倫孝
    • Organizer
      ConBio2017
    • Related Report
      2017 Annual Research Report
  • [Presentation] 肝細胞におけるレドックス依存性ネクロプトーシスの動態解析2017

    • Author(s)
      芳賀 早苗、菅野 憲、小澤 岳昌、森田 直樹、浅野 真未、伊 敏、尾崎 倫孝
    • Organizer
      ConBio2017
    • Related Report
      2017 Annual Research Report
  • [Presentation] マウス脂肪化肝細胞・脂肪肝に対するビルベリーの抑制効果の検討2017

    • Author(s)
      芳賀 早苗、荘厳 哲哉、伊 敏、森田 直樹、浅野 真未、尾崎 倫孝
    • Organizer
      第38回日本肥満学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 肝核内受容体FXRはp62/SQSTM1およびSHPを経由して、それぞれ抗酸化・細胞保護効果、脂肪化抑制効果を示す2017

    • Author(s)
      尾崎 倫孝、芳賀 早苗、伊 敏
    • Organizer
      第24回肝細胞研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 脂肪化肝細胞・脂肪肝に対するビルベリーの効果とその機序の検討2017

    • Author(s)
      芳賀 早苗、荘厳 哲哉、伊 敏、森田 直樹、浅野 真未、尾崎 倫孝
    • Organizer
      第24回肝細胞研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 肝細胞におけるプログラム細胞死(アポトーシス、ネクロプトーシス)の動的解析 Dynamic analysis of apoptotic and necroptotic death of hepatocytes with optical probes2016

    • Author(s)
      芳賀 早苗, 菅野 憲, 小澤 岳昌, 尾崎 倫孝
    • Organizer
      第39回日本分子生物学会年会
    • Related Report
      2016 Annual Research Report
  • [Presentation] 光技術を用いた臓器・細胞機能評価と制御の可能性2016

    • Author(s)
      尾崎倫孝,芳賀早苗,小澤岳昌,森田直樹,浜田俊幸
    • Organizer
      第43回日本臓器保存生物医学会学術集会
    • Related Report
      2016 Annual Research Report
  • [Presentation] ビルベリー糖尿病性網膜症初期病変抑制効果の検討Cytoprotective and Antioxidative Roleof Bilberry in Early Diabetic Retinopathy.2016

    • Author(s)
      芳賀 早苗、荘厳 哲哉、森田 直樹、浅野 真未、尾崎 倫孝
    • Organizer
      第89回日本生化学会大会
    • Related Report
      2016 Annual Research Report
  • [Presentation] FXRを起点とした脂肪肝傷害抑制と 脂肪化改善の機序2016

    • Author(s)
      尾崎 倫孝、芳賀 早苗、森田 直樹
    • Organizer
      第25回日本肝臓医生物学研究会
    • Related Report
      2016 Annual Research Report
  • [Presentation] 光プローブをもちいた時空間的病態解析と積極的病態制御の試み2016

    • Author(s)
      尾崎 倫孝、芳賀 早苗、小澤 岳昌、山田 勇磨
    • Organizer
      第71回日本消化器外科学会総会
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] ビルベリーによる非アルコール性脂肪肝炎(NASH)の予防に向けた基礎的検討2016

    • Author(s)
      芳賀 早苗、荘厳 哲哉、森田 直樹、浅野 真未、尾崎 倫孝
    • Organizer
      第23回肝細胞研究会
    • Related Report
      2016 Annual Research Report
  • [Presentation] Long-term ex vivo and in vivo monitoring of tumor progression by using dual luciferases.2016

    • Author(s)
      Naoki Morita, Sanae Haga, Yoshihiro Ohmiya, Michitaka Ozaki
    • Organizer
      19th International Symposium on Bioluminescence & Chemiluminescence (ISBC2016)
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Optical evaluation and monitoring of oxidative stress & damage in vivo.2016

    • Author(s)
      Sanae Haga, Takeaki Ozawa, Naoki Morita, Mami Asano, James Remington, Michitaka Ozaki.
    • Organizer
      19th International Symposium on Bioluminescence & Chemiluminescence (ISBC2016)
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Evaluation of necroptotic cell death by monitoring RIP1/RIP3 interaction in hepatocytes. (肝細胞におけるRIP1/RIP3結合能のモニタリングによるネクロプトーシス評価の試み)2015

    • Author(s)
      芳賀 早苗、菅野 憲、小澤 岳昌、尾崎 倫孝
    • Organizer
      BMB2015
    • Place of Presentation
      神戸ポートアイランド(神戸市)
    • Year and Date
      2015-12-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] p62/SQSTM1 を基軸とした新たな肝臓・肝細胞保護・機能維持法の探索2015

    • Author(s)
      尾崎 倫孝、芳賀 早苗、森田 直樹、伊 敏
    • Organizer
      第42回日本臓器保存生物医学会学術集会
    • Place of Presentation
      いわて県民情報交流センター(盛岡市)
    • Year and Date
      2015-11-13
    • Related Report
      2015 Annual Research Report

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Published: 2015-04-16   Modified: 2022-11-04  

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