學術報告
報告名稱：Therapeutic targeting nudix hydrolase 1 creates a MYC-driven metabolic vulnerability
報告人：武漢大學醫學研究院 卿國良教授
報告時間：2023年12月4日（星期一）下午3點10分—4點10分
報告地點：伟德首页官网437會議室
主持人：曹軒
卿國良教授簡介：
武漢大學醫學研究院教授、博導，國家傑青，醫學研究院副院長，教育部免疫與代謝前沿科學中心副主任。國家自然科學基金委和科技部各類項目會評專家。研究方向：代謝異常與腫瘤發生發展。承擔國家傑出青年科學基金、國家自然科學基金重點項目和科技部重大研究計劃等各類課題10餘項。在Nature Biotechnology、Cancer Cell、Molecular Cell、Nature Communications、Science Advances、Cell Reports等主流期刊發表SCI文章40餘篇。獲國際發明專利1項，已成功轉讓Takara公司。
學術報告主要内容：
Tumor cells must rewire nucleotide synthesis to satisfy the demands of unbridled proliferation. Meanwhile, they exhibit augmented reactive oxygen species (ROS) production which paradoxically damages DNA and free dNTPs. How these metabolic processes are integrated to fuel tumorigenesis remains to be investigated. MYC family oncoproteins are central regulators that coordinate nucleotide synthesis and ROS generation to drive the development of numerous human cancers. We herein performed a CRISPR-based functional screen targeting metabolic genes and identified nudix hydrolase 1 (NUDT1) as a MYC-driven metabolic dependency. Mechanistically, MYC orchestrated the balance of two metabolic pathways that act in parallel, the NOX4-ROS pathway and the PLK1-NUDT1 nucleotide-sanitizing pathway. We describe LC-1-40 as the first-in-class degrader that potently and selectively depletes NUDT1 in vivo. Administration of LC-1-40 disrupted MYC-controlled metabolic homeostasis, resulting in excessive nucleotide oxidation, cytotoxicity and therapeutic responses in patient-derived xenografts. Thus, pharmacological targeting of NUDT1 represents an actionable MYC-driven metabolic liability.
國家自然科學基金申報與評審經驗交流座談會：
2023年12月4日（星期一）下午4點15分—5點15分，伟德首页官网305會議室
