报 告 人

卿国良 武汉大学医学研究院教授

报告时间

2023年12月4日（星期一）下午3:10 - 4:10

报告地点

医学院437会议室

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报告内容简介：

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.

报告人简介：

武汉大学医学研究院教授、博导，国家杰青，医学研究院副院长，教育部免疫与代谢前沿科学中心副主任。国家自然科学基金委和科技部各类项目会评专家。研究方向：代谢异常与肿瘤发生发展。承担国家杰出青年科学基金、国家自然科学基金重点项目和科技部重大研究计划等各类课题10余项。在Nature Biotechnology、Cancer Cell、Molecular Cell、Nature Communications、Science Advances、Cell Reports等主流期刊发表SCI文章40余篇。获国际发明专利1项，已成功转让Takara公司。

承办单位

医学院

发布日期

2023年11月27日

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