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Development of new preventive or therapeutic strategies for hematopoietic neoplasms based on metabolic analysis.

Research Project

Project/Area Number 21K19502
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 54:Internal medicine of the bio-information integration and related fields
Research InstitutionKanazawa University

Principal Investigator

Hirao Atsushi  金沢大学, がん進展制御研究所, 教授 (90343350)

Co-Investigator(Kenkyū-buntansha) 加藤 将夫  金沢大学, 薬学系, 教授 (30251440)
Project Period (FY) 2021-07-09 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2022: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords代謝 / 代謝物
Outline of Research at the Start

本研究では、造血器腫瘍患者および疾患モデルを研究対象とし、メタボロミクスによる代謝物の網羅的探索法の確立、代謝物の機能解析法の確立を進め、造血器腫瘍の治療および予防に資する代謝物探索システムの構築を目指す。本研究では、観測対象を特定しないメタボロミクス法を用いて、幅広く有用な代謝物を探索し、代謝物による造血制御という新たな研究領域への展開を目指す。

Outline of Final Research Achievements

In this study, we aimed to establish a metabolite discovery system that contributes to the treatment and prevention of hematopoietic tumors by (1) conducting a comprehensive search for metabolites by metabolomics and (2) analyzing the functions of metabolites in disease models. As a result of our analysis, we observed that myeloproliferative disease was accelerated by a long-term high-fat diet. Metabolomic analysis revealed that many metabolites are altered by a high-fat diet, and that a metabolite had functions that inhibited the pathophysiology of the disease. Further development based on the findings of this study may lead to the identification of disease biomarkers and the development of therapeutic agents in the future.

Academic Significance and Societal Importance of the Research Achievements

昨今、様々な病態解明を目指して、ゲノミクス、プロテオミクス、エピジェネティクス解析など生体サンプルの網羅的解析が進んでいる。今回、我々は最新の質量分析法によるデータ収集、インフォマティクス解析を実施し、重要な代謝物を同定するシステムを構築することができた。本研究は,代謝物という観点から造血器疾患の病態の解明に挑む新しいアプローチとして、多くの疾患研究の次世代型プロトタイプになり得る。

Report

(3 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • Research Products

    (14 results)

All 2023 2022 2021

All Journal Article (8 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 8 results,  Open Access: 7 results) Presentation (5 results) (of which Int'l Joint Research: 2 results,  Invited: 5 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] MEK5-ERK5 Axis Promotes Self-renewal and Tumorigenicity of Glioma Stem Cells2023

    • Author(s)
      Fukasawa Kazuya、Lyu Jiajun、Kubo Takuya、Tanaka Yuki、Suzuki Akane、Horie Tetsuhiro、Tomizawa Akane、Osumi Ryoma、Iwahashi Sayuki、Tokumura Kazuya、Murata Misato、Kobayashi Masaki、Todo Tomoki、Hirao Atsushi、Hinoi Eiichi
    • Journal Title

      Cancer Research Communications

      Volume: 3 Issue: 1 Pages: 148-159

    • DOI

      10.1158/2767-9764.crc-22-0243

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Therapeutic advantage of targeting lysosomal membrane integrity supported by lysophagy in malignant glioma2022

    • Author(s)
      Jing Yongwei、Kobayashi Masahiko、Vu Ha Thi、Kasahara Atsuko、Chen Xi、Pham Loc Thi、Kurayoshi Kenta、Tadokoro Yuko、Ueno Masaya、Todo Tomoki、Nakada Mitsutoshi、Hirao Atsushi
    • Journal Title

      Cancer Science

      Volume: 113 Issue: 8 Pages: 2716-2726

    • DOI

      10.1111/cas.15451

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] RHEB is a potential therapeutic target in T cell acute lymphoblastic leukemia2022

    • Author(s)
      Pham Loc Thi、Peng Hui、Ueno Masaya、Kohno Susumu、Kasada Atuso、Hosomichi Kazuyoshi、Sato Takehiro、Kurayoshi Kenta、Kobayashi Masahiko、Tadokoro Yuko、Kasahara Atsuko、Shoulkamy Mahmoud I.、Xiao Bo、Worley Paul F.、Takahashi Chiaki、Tajima Atsushi、Hirao Atsushi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 621 Pages: 74-79

    • DOI

      10.1016/j.bbrc.2022.06.089

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Intracellular metabolic adaptation of intraepithelial CD4+CD8αα+ T lymphocytes2022

    • Author(s)
      Harada Y, Sujino T, Miyamoto K, Nomura E, Yoshimatsu Y, Tanemoto S, Umeda S, Ono K, Mikami Y, Nakamoto N, Takabayashi K, Hosoe N, Ogata H, Ikenoue T, Hirao A, Kubota Y, Kanai T.
    • Journal Title

      iScience

      Volume: 25 Issue: 4 Pages: 104021-104021

    • DOI

      10.1016/j.isci.2022.104021

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The Role of Nutrients in Maintaining Hematopoietic Stem Cells and Healthy Hematopoiesis for Life2022

    • Author(s)
      Yuko Tadokoro and Atsushi Hirao
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Issue: 3 Pages: 1574-1589

    • DOI

      10.3390/ijms23031574

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] SMURF2 phosphorylation at Thr249 modifies glioma stemness and tumorigenicity by regulating TGF-β receptor stability2022

    • Author(s)
      Hiraiwa Manami、Fukasawa Kazuya、Iezaki Takashi、Sabit Hemragul、Horie Tetsuhiro、Tokumura Kazuya、Iwahashi Sayuki、Murata Misato、Kobayashi Masaki、Suzuki Akane、Park Gyujin、Kaneda Katsuyuki、Todo Tomoki、Hirao Atsushi、Nakada Mitsutoshi、Hinoi Eiichi
    • Journal Title

      Communications Biology

      Volume: 5 Issue: 1 Pages: 22-22

    • DOI

      10.1038/s42003-021-02950-0

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The GPI-anchored protein CD109 protects hematopoietic progenitor cells from undergoing erythroid differentiation induced by TGF-β2021

    • Author(s)
      Tanabe Mikoto、Hosokawa Kohei、Nguyen Mai Anh Thi、Nakagawa Noriharu、Maruyama Kana、Tsuji Noriaki、Urushihara Ryota、Espinoza Luis、Elbadry Mahmoud I.、Mohiuddin Md、Katagiri Takamasa、Ono Masanori、Fujiwara Hiroshi、Chonabayashi Kazuhisa、Yoshida Yoshinori、Yamazaki Hirohito、Hirao Atsushi、Nakao Shinji
    • Journal Title

      Leukemia

      Volume: 36 Issue: 3 Pages: 847-855

    • DOI

      10.1038/s41375-021-01463-3

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] CDK8 maintains stemness and tumorigenicity of glioma stem cells by regulating the c-MYC pathway2021

    • Author(s)
      Fukasawa K, Kadota T, Horie T, Tokumura K, Terada R, Kitaguchi Y, Park G, Ochiai S, Iwahashi S, Okayama Y, Hiraiwa M, Yamada T, Iezaki T, Kaneda K, Yamamoto M, Kitao T, Shirahase H, Hazawa M, Wong RW, Todo T, Hirao A, Hinoi E.
    • Journal Title

      Oncogene

      Volume: ー Issue: 15 Pages: 2803-2815

    • DOI

      10.1038/s41388-021-01745-1

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Cell fate determination mediated by nutrient-derived metabolites in malignant progression.2023

    • Author(s)
      Asushi Hirao
    • Organizer
      2023 Normal/Malignant Hematopoiesis and Novel Therapies for Hematologic Malignancies Symposium
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 栄養および免疫制御を介した造血幹細胞の発がん・老化,2022

    • Author(s)
      平尾敦
    • Organizer
      第8回がんと代謝研究会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Cell fate decision by metabolic regulation in hematopoietic stem cell homeostasis and leukemogenesis.2021

    • Author(s)
      Atsushi Hirao
    • Organizer
      The 39th Sapporo International Cancer Symposium
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Cell fate determination mediated by nutrient-derived metabolites in tumor development and malignant progression.2021

    • Author(s)
      Atsushi Hirao
    • Organizer
      第80回日本癌学会学術総会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 栄養代謝による細胞運命決定とがん2021

    • Author(s)
      平尾敦
    • Organizer
      第94回日本生化学大会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Patent(Industrial Property Rights)] 腫瘍治療用医薬組成物2021

    • Inventor(s)
      1.平尾敦, Jing Y, 小林昌彦, 中田光俊
    • Industrial Property Rights Holder
      1.平尾敦, Jing Y, 小林昌彦, 中田光俊
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Related Report
      2021 Research-status Report

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Published: 2021-07-13   Modified: 2024-01-30  

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