Forward genetic identification of new players in vitamin D signaling.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06950
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Fukushima Medical University
• Principal Investigator: Sugimoto Kotaro 福島県立医科大学, 医学部, 講師 (40791009)
• Co-Investigator(Kenkyū-buntansha): 小林 信 福島県立医科大学, 医学部, 助教 (60761947)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ビタミンD / がん / 順遺伝学 / CRISPR / ゲノム編集 / 核内受容体

Outline of Final Research Achievements

Nuclear receptors are transcription factors that regulate gene transcription by binding to lipid ligands. However, previous studies have been biased toward the search for novel ligands and have failed to identify endogenous regulators that affect post-translational modifications. In this study, we used CRISPR screening, a sequential genetic method, to comprehensively extract endogenous regulators of the vitamin D receptor, one of the nuclear receptors. This candidate molecules might be potential therapeutic targets for various diseases including malignant tumors.

Free Research Field

実験病理学

Academic Significance and Societal Importance of the Research Achievements

ビタミンDシグナルはがん治療の標的になり得るが、ビタミンDサプリメントはがんの罹患率や予後を改善しない。よってがん細胞内で減弱しているビタミンDシグナルを活性化させることが有効と思われるが、従来の研究は主に新規脂質リガンドの探索に偏っており、ビタミンDシグナル経路のリン酸化異常や原因キナーゼの理解は進んでいない。本研究でビタミンDシグナルの活性化に関わる内因性蛋白質が明らかになれば、これを標的とする全く新しいがんの予防法や治療法の開発に繋がる。