本团队是一支专注于肿瘤代谢和代谢性脂肪肝相关研究的科研团队,致力于通过前沿的研究方法和技术,解决该领域的关键科学问题,推动学科的发展。
研究方向:
1. 肿瘤代谢重编程的化学机制及干预策略;
2. 代谢性脂肪肝的调控机制及药物研发;
研究兴趣主要在于揭示代谢相关疾病的调控机制,并进行创新药物的研发。
主要研究成果:
1. 发现合成嘧啶的酶能形成跨线粒体外膜的复合物(嘧啶小体),调控嘧啶从头合成及铁死亡,并在乏氧下促进谷氨酰胺中的氮通过形成二氢乳清酸分泌出去(新的氨代谢途径);
2. 发现细胞吸收脂肪酸的新途径,并阐述其在肿瘤及脂肪肝发生发展中的重要作用;
3. 揭示电子堆积(还原应激)驱动代谢重编及诱导细胞死亡的化学本质和分子机制,并提出了可预测新发现的理论模型等。
研究成果主要发表在Cancer Cell、Nature Cell Biology(2篇)、Nature Communications(4篇)、Journal of Experimental Medicine(2篇)、Science Advances、EMBO Journal等国际学术刊物上,提出了“电子传递平衡理论”为肿瘤代谢重编程提供了理论框架,发现并定义了“嘧啶小体”、揭示了其生理意义和调控机制,被国际同行高度评价、誉为“该领域的突破性进展”。
团队成员主要包括阳荣辉、蒋瑀涵、曲亚楠、侯彭姣等青年骨干成员及博士后、研究生。
代表性论文:
1. Zhai X, Yang R, Chu Q, Guo Z, Hou P, Li X, Bai C, Lu Z, Qiao L, Fu Y, Niu J, Li B*. AMPK-regulated glycerol excretion maintains metabolic crosstalk between reductive and energetic stress. Nat Cell Biol, 27(1):141-153. doi:10.1038/s41556-024-01549-x. (2025)
2. Yang C, Zhao Y, Wang L, Guo Z, Ma L, Yang R, Wu Y, Li X, Niu J, Chu Q, Fu Y, Li B*. De novo pyrimidine biosynthetic complexes support cancer cell proliferation and ferroptosis defense. Nat Cell Biol, 25(6):836-847. doi: 10.1038/s41556-023-01146-4. (2023). Comment in “The pyrimidinosome is cancer's Achilles' heel. Nat Cell Biol, 25(6):798-799. doi: 10.1038/s41556-023-01159-z (2023)”; Comment in “The pyrimidinosome: Orchestrating pyrimidine biosynthesis and ferroptosis defense. Mol Cell, 83(16):2837-2839. doi:10.1016/j.molcel.2023.07.013 (2023)”.
3. Li L*, Wang X, Hu K, Liu X, Qiu L, Bai C, Cui Y, Wang B, Wang Z, Wang H, Cheng R, Hua J, Hai L, Wang M, Liu M, Song Z, Xiao C*, Li B*. ZNF133 is a potent suppressor in breast carcinogenesis through dampening L1CAM, a driver for tumor progression. Oncogene, 42(27):2166-2183. doi: 10.1038/s41388-023-02731-5. (2023)
4. Chu Q, An J, Liu P, Song Y, Zhai X, Yang R. Niu J, Yang C, Li B*. Repurposing a tricyclic antidepressant in tumor and metabolism disease through fatty acid uptake inhibition. J Exp Med, 220(3):e20221316. doi: 10.1084/jem.20221316. (2023). Comment in “Stopping the fat: Repurposing an antidepressant for cancer treatment. J Exp Med, 220 (3):e20222097. doi: 10.1084/jem.20222097 (2023)”.
5. Chu Q, Liu P, Song Y, Yang R, An J, Zhai X, Niu J, Yang C, Li B*. Stearate-derived very long-chain fatty acids are indispensable to tumor growth. EMBO J, 42(2):e111268. doi: 10.15252/embj.2022111268. (2023)
6. Yang R, Yang C, Ma L, Zhao Y, Guo Z, Niu J, Chu Q, Ma Y, Li B*. Identification of purine biosynthesis as an NADH-sensing pathway to mediate energy stress. Nature Commun, 13(1):7031. doi: 10.1038/s41467-022-34850-0. (2022)
7. Zhong B, Liu M, Bai C, Ruan Y, Wang Y, Qiu L, Hong Y, Wang X, Li L*, Li B*. Caspase-8 induces lysosome-associated cell death in cancer cells. Mol Ther, 28(4):1078-1091. (2020)
8. Liu M, Wang Y, Yang C, Ruan Y, Bai C, Chu Q, Cui Y, Chen C, Ying G, Li B*. Inhibiting both proline biosynthesis and lipogenesis synergistically suppresses tumor growth. J Exp Med, 217(3): e20191226. doi: 10.1084/jem.20191226. (2020)
9. Wang Y, Bai C, Ruan Y, Liu M, Chu Q, Qiu L, Yang C, Li B*. Coordinative metabolism of glutamine carbon and nitrogen in proliferating cancer cells under hypoxia. Nat Commun, 10(1):201. doi:10.1038/s41467-018-08033-9. (2019)
10. Zhang J, Wang X, Cui W, Wang W, Zhang H, Liu L, Zhang Z, Li Z, Ying G, Zhang N, Li B*. Visualization of caspase-3-like activity in cells using a genetically encoded fluorescent biosensor activated by protein cleavage. Nat Commun, 4:2157. doi:10.1038/ncomms3157. (2013).
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