Lecture time

Lecture location

Conference Room 302, Building 1, Jinfeng Laboratory

Xu Daqian ， Qiushi Distinguished Professor of Zhejiang University, permanent full professor of the School of Medicine, doctoral supervisor, National Natural Science Foundation of China Youth A (Former National Distinguished Young Scholar), winner of the Overseas Excellent Youth Project, chief scientist of the Youth Project of the National Key R&D Program, core member of Zhejiang Province’s leading innovation and entrepreneurship basic research team, has long been committed to tumor metabolism research, and has published many papers as the corresponding author (including co-authors) in well-known academic journals such as Nature, Nature Cell Biology (4 articles), Nature Metabolism, Nature Chemical Biology (3 articles), Journal of Experimental Medicine (2 articles), and PNAS. Won the Huaxia Youth Medical Science and Technology Award, the Young Scientist Award of the Chinese Anti-Cancer Association, the Young Scholar Award of the Chinese Society of Immunology, the First Prize of Zhejiang Natural Science Award, and the China Industry-Academic-Research Collaboration Innovation Individual Award. ； As the project leader, he presides over the National Key R&D Program Youth Project, National Natural Science Foundation Youth A, Regional Joint Key, Major Research Plan Cultivation, General (X2) Project, Zhejiang Provincial Natural Science Foundation Outstanding Youth, Major Project, etc. Served as an editorial board member of BMC Biology and Science Bulletin magazines, a member of the Chinese Society of Cell Biology - Tumor Cell Biology Branch, and a member of the Chinese Anti-Cancer Association - Tumor Rhythm and Hypoxic Oncology Committee. 。

Pancreatic ductal adenocarcinoma (PDAC) has limited response to neoadjuvant chemotherapy, highlighting the urgent need to develop novel combination treatment strategies and gain a deeper understanding of the metabolic determinants of chemotherapy resistance. We found that the valine catabolic enzyme methylmalonate semialdehyde dehydrogenase (MMSDH) is a key driver of gemcitabine resistance. Under hypoxic conditions, GCN5 mediates the lactylation modification of MMSDH at the K113 site. Lactylated MMSDH interacts with ACSL4 to generate propionyl-CoA, thereby promoting KAT8-mediated propionylation modification of ACSL4 at the K606 site. This modification enhances the binding of ACSL4 to HSC70 and promotes ACSL4 degradation through the chaperone-mediated autophagy pathway. Particularly important is that in patients with PDAC, MMSDH-mediated ACSL4 propionylation levels are significantly associated with low ACSL4 expression and adverse reactions to NAC. Dietary restriction of valine intake combined with gemcitabine can synergistically induce ferroptosis and effectively inhibit tumor growth. Blocking K113 lactylation of MMSDH disrupts this signaling axis, enhances gemcitabine-induced ferroptosis, and inhibits tumor progression. These findings reveal a previously unknown mechanism to escape ferroptosis through regulation of valine metabolism and ACSL4, suggesting that the GCN5–MMSDH–ACSL4 axis may serve as a potential therapeutic target to improve the chemosensitivity of PDAC.

Qian Xu , National Overseas High-level Young Talent (Youth Thousand Talents), Jiangsu Distinguished Professor, Jiangsu Provincial “Double Entrepreneurship Team” Leading Talent, Director of the Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Director (concurrently) of the Scientific Research Sharing Platform, Deputy Director of the Cultivation and Construction Site of the National Key Laboratory of Tumor Biomarkers and Precision Prevention and Treatment, and his research results were published as the corresponding author in Nat Cell Biol (2026a), Sci Transl Med (2024), Mol Cell (2022a, 2022b), Nat Commun (2023), Cancer Res (2023 cover), Cell Rep (2023) and other journals； Published as co-corresponding author in Nat Cell Biol (2026b), Nat Cancer (2026), Mol Cell (2019a, 2019b), Cancer Lett (2025) and other journals. He serves as a standing member of the Hypoxic Oncology Committee of the Chinese Anti-Cancer Association, a member of the Cell Metabolism Branch of the Chinese Society of Cell Biology, a member of the Neuro-Tumor Branch of the Chinese Society of Neuroscience, a member of the Nutritional Toxicology Branch of the Chinese Nutrition Society, and an executive director of the Jiangsu Provincial Nutrition Society. He also undertakes projects such as the National Natural Science Foundation of China and the National Health Commission’s Four Major Chronic Diseases (Project Leader).

The common mechanism by which the cancer-promoting metabolite fumaric acid exerts its cancer-promoting effects； The mechanism by which fumaric acid regulates iron distribution and promotes the stemness maintenance of glioma stem cells ； Mechanisms by which stress granules maintain iron homeostasis and limit ferroptosis.