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2020 Fiscal Year Final Research Report

A chemical genomics approach to elucidate the regulation of unfolded protein response

Research Project

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Project/Area Number 19K23817
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0801:Pharmaceutical sciences and related fields
Research InstitutionKawasaki Medical School

Principal Investigator

Kitakaze Keisuke  川崎医科大学, 医学部, 助教 (80840545)

Project Period (FY) 2019-08-30 – 2021-03-31
Keywordsケミカルゲノミクス / 小胞体ストレス応答 / CRISPR / TRPV1 / VEGFR2
Outline of Final Research Achievements

The cell has an adaptive system against endoplasmic reticulum stress called unfolded protein response (UPR). The discovery of novel proteins that regulate the UPR and the elucidation of their mechanisms will lead to the development of therapeutic targets for diseases. In this study, we performed a comprehensive screening for proteins that regulate the UPR using a compound library and UPR reporter cells and identified TRPV1 and VEGFR2 as candidate proteins. Our data suggest TRPV1 activates the UPR by altering ion concentrations in the ER, and VEGFR2 suppresses the UPR by contributing to the IRE1-XBP1 pathway.

Free Research Field

生物系薬学

Academic Significance and Societal Importance of the Research Achievements

ケミカルゲノミクス的手法は、発現量の解析だけでは発見できない新規UPR制御タンパク質を探索できる点に優れており、本研究では創薬標的になりやすく、小胞体機能への関与の可能性が高い分子群に着目した。本研究によりUPR制御タンパク質候補を発見したことにより、小胞体ストレスを原因とする疾患の発症機序の解明や治療薬開発につながることが期待される。加えて、本研究は探索研究の方法論確立という側面も持っており、本研究の手法は様々なシグナル伝達経路における探索研究にも応用可能であり、生命科学の広い分野に対して有用性を示すものである。

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Published: 2022-01-27  

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