张迪
北京大学生命科学学院研究员/助理教授
北大-清华生命科学联合中心PI
电子邮件：zhangdi@pku.edu.cn
实验室主页: http://di-zhang-lab.com
个人主页：https://scholar.google.com/citations?user=vU5Sz28AAAAJ&hl=en
研究领域：
细胞的各种生命活动都与代谢紧密相连，代谢不仅为细胞提供能量和构建模块，还通过多种方式调控细胞功能。我们的研究团队致力于揭示代谢如何通过复杂的机制调控关键的生理活动，从而使细胞适应环境，以及这些代谢途径异常在重大疾病发生发展中的作用机制。我们通过运用经典的生化、细胞和分子生物学技术，并结合最新的多组学分析方法，在国际上首次报道了多种由细胞代谢物驱动的新型蛋白质修饰，包括赖氨酸乳酰化（由乳酸介导）和赖氨酸β-羟基丁酰化（由酮体介导）等。
研究的具体方向包括：
1. 发现由代谢物驱动的新型蛋白质修饰，并研究其功能，以揭示代谢物对蛋白质功能调控的新途径。
2. 探索代谢物如何调控染色质的结构和功能，从而影响基因表达和细胞命运的新机制。
3. 研究代谢酶在代谢适应和代谢调控中的新机制，进一步理解代谢过程在细胞生理和疾病中的复杂作用。
代表性研究成果：
(*Co-first author, # Corresponding author)
(1) Zhang D#, Gao J, Zhu Z, Mao Q, Xu Z, Singh PK, Rimayi CC, Moreno-Yruela C, Xu S, Li G, Sin YC, Chen Y, Olsen CA, Snyder NW, Dai L, Li L, Zhao Y. (2024). Lysine L-lactylation is the dominant lactylation isomer induced by glycolysis. Nat Chem Biol. Jul 19. doi: 10.1038/s41589-024-01680-8. Epub ahead of print.
(2) Ren H, Zhang D#. (2024). Lactylation constrains OXPHOS under hypoxia. Cell Res. https://doi.org/10.1038/s41422-023-00872-6.
(3) Gao J, Sheng X, Du J, Zhang D, Han C, Chen Y, Wang C, Zhao Y. (2023). Identification of 113 new histone marks by CHiMA, a tailored database search strategy. Sci Adv. 9(14): eadf1416.
(4) Moreno-Yruela C, Zhang D*, Wei W, Bæk M, Liu W, Gao J, Danková D, Nielsen AL, Bolding JE, Yang L, Jameson ST, Wong J, Olsen CA, Zhao Y. (2022). Class I histone deacetylases (HDAC1-3) are histone lysine delactylases. Sci Adv. 8(3): eabi6696.
(5) Huang H, Zhang D*, Weng Y, Delaney K, Tang Z, Yan C, Qi S, Peng C, Cole PA, Roeder RG, Zhao Y. (2021). The regulatory enzymes and protein substrates for the lysine β-hydroxybutyrylation pathway. Sci Adv. 7(9): eabe2771.
(6) Zhang D*, Tang Z*, Huang H, Zhou G, Cui C, Weng Y, Liu W, Kim S, Lee S, Perez-Neut M, Czyz D, Hu R, Ye Z, He M, Zheng YG, Shuman H, Ding J, Dai L, Ren B, Robert RG, Becker L, Zhao Y. (2019). Metabolic regulation of gene expression by histone lactylation. Nature. 574: 575-580.
(7) Huang H, Zhang D, Wang Y, Perez-Neut M, Han Z, Zheng YG, Hao Q, Zhao Y. (2018). Lysine benzoylation is a histone mark regulated by SIRT2. Nat Commun. 9(1): 3374.
(8) Sabari BR*, Zhang D*, Allis CD, Zhao Y. (2017). Metabolic Regulation of Gene Expression through Differential Histone Acylation. Nat Rev Mol Cell Biol. 18(2): 90-101.
(9) Xie Z*, Zhang D*, Chung D*, Tang Z, Huang H, Dai L, Qi S, Li J, Colak G, Chen Y, Xia C, Peng C, Ruan H, Kirkey M, Wang D, Jensen LM, Kwon OK, Lee S, Pletcher SD, Tan M, Lombard DB, White KP, Zhao H, Li J, Roeder RG, Yang X, Zhao Y. (2016). Metabolic Regulation of Gene Expression by Histone Lysine beta-hydroxybutyrylation. Mol Cell. 62(2): 194-206.
(10) Goudarzi A*, Zhang D*, Huang H, Barral S, Kwon OK, Qi S, Tang Z, Buchou T, Vitte AL, He T, Cheng Z, Montellier E, Gaucher J, Curtet S, Debernardi A, Charbonnier G, Puthier D, Petosa C, Panne D, Rousseaux S, Roeder RG, Zhao Y, Khochbin S. (2016). Dynamic Competing Histone H4 K5K8 Acetylation and Butyrylation Are Hallmarks of Highly Active Gene Promoters. Mol Cell. 62(2): 169-80.
