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Development of a novel therapy for sickle cell disease by Nrf2 activation

Research Project

Project/Area Number 16H06639
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field Pathological medical chemistry
Research InstitutionTohoku University

Principal Investigator

Keleku-Lukwete Nadine  東北大学, 医学系研究科, 助教 (40781761)

Project Period (FY) 2016-08-26 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordssickle cell disease / Nrf2 / Keap1 knockout / Myeloid cells / endothelial cells / Sickle cell disease / Nrf2 activation / Oxidative stress / Specific activation / oxidative stress
Outline of Final Research Achievements

Our research project was aimed to understand the mechanisms of specific-cell response to the activation of Nrf2 and how they contribute to the amelioration of the sickle cell disease (SCD) phenotype. We studied the function of Nrf2 in myeloid and endothelial cells and it influence to the surrounding organs by using mutant mice harboring the globin mutation, Keap1 deletion in either myeloid cells (SCD::Keap1F/F::LysM-Cre mice) or endothelial cells (SCD::Keap1F/F::Tie1-Cre mice). We collected peritoneal macrophages and cultured primary pulmonary endothelial cells for the cell specificity experiments; and some tissues we collected and to perform histological and hematological analysis; biochemistry; IMS and LC-mass; and genes expression (using PCR and RNA- sequencing). All the results are summarized in the manuscript that we submitted to Blood Advances journal for publication which is currently under revision.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • Research Products

    (7 results)

All 2018 2017 2016 Other

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

  • [Int'l Joint Research] University of Michigan(米国)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] An Overview of the Advantages of KEAP1-NRF2 System Activation During Inflammatory Disease Treatment2018

    • Author(s)
      Keleku-Lukwete Nadine、Suzuki Mikiko、Yamamoto Masayuki
    • Journal Title

      Antioxid Redox Signal

      Volume: - Issue: 17 Pages: 1746-1755

    • DOI

      10.1089/ars.2017.7358

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Halofuginone enhances the chemo-sensitivity of cancer cells by suppressing NRF2 accumulation.2017

    • Author(s)
      Tsuchida K, Tsujita T, Hayashi M, Ojima A, Keleku-Lukwete N, Katsuoka F, Otsuki A, Kikuchi H, Oshima Y, Suzuki M, Yamamoto M.
    • Journal Title

      Free Radic Biol Med

      Volume: 103 Pages: 236-247

    • DOI

      10.1016/j.freeradbiomed.2016.12.041

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Overview of redox regulation by Keap1-Nrf2 system in toxicology and cancer.2016

    • Author(s)
      Suzuki M, Otsuki A, Keleku-Lukwete N, Yamamoto M.
    • Journal Title

      Curr Opin in Toxicol

      Volume: 1 Pages: 29-36

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Presentation] Sulforaphane relives inflammation and organ damage in sickle cell disease by inducing Nrf2.2017

    • Author(s)
      Harit Panda, Nadine Keleku-Lukwete, Mikiko Suzuki, Masayuki Yamamoto.
    • Organizer
      日本生化学会東北支部第83回例会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Nrf2 induction by oral administration of glucoraphanin relieves tissue damage in sickle cell disease.2017

    • Author(s)
      Harit Panda、Nadine Keleku-Lukwete、Mikiko Suzuki、Masayuki Yamamoto.
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Insight mechanism underlying the importance of Nrf2 in sickle cell disease.2016

    • Author(s)
      Nadine Keleku-Lukwete、Harit Panda、長沼絵里子、鈴木未来子、山本雅之.
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台国際センター, 仙台
    • Year and Date
      2016-09-25
    • Related Report
      2016 Annual Research Report

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Published: 2016-09-02   Modified: 2022-05-23  

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