Biography
Dr. Di Zhang received his B.S. degree in Basic Medical Science at Peking University Health Science Center, China in 2010, and Ph.D. degree in Biochemistry and Molecular Biology at Peking University Health Science Center, in 2013. As a graduate student, he focused on transcriptional regulation using estrogen receptor alpha positive breast cancer as a model system. Then he moved to Chicago (USA) and did his postdoctoral research in Yingming Zhao’s laboratory at the University of Chicago from 2013 to 2021. In Chicago, he identified two new types of histone modifications that are derived from cellular metabolites (lactate and ketone body, respectively). Dr. Zhang joined School of Life Sciences and PKU-THU Joint Center for Life Sciences (CLS) at Peking University in March 2021 as a Principal Investigator.
Education
2010 - 2013 Ph.D. Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, China
2005 - 2010 B.S. Basic Medical Science, Peking University Health Science Center, Beijing, China
Professional Experience
2021.03 – present Assistant Professor, Peking University School of Life Sciences, Beijing, China
2021.03 – present Principal Investigator, Peking-Tsinghua Center for Life Sciences, Beijing, China
2013.09 – 2021.01 Postdoc, Ben May Department for Cancer Research, The University of Chicago, USA
Honors and Awards
Peking University Boya Young Fellow, 2021
Bayer Investigator, 2021
Yi Fang Investigator, 2021
Professional Society Affiliations
2021-2025， Chinese Society of Biochemistry and Molecular Biology, Proteomics Division, Member
Research Interests
Cellular functions are intricately intertwined with metabolic processes, which are not only the source of cellular energy but also key regulators of various physiological activities. Our research team employs classic biochemical, cellular, and molecular biology techniques, combined with cutting-edge omics technologies, to delve into the mechanisms by which metabolic adaptation regulates important physiological activities in cells and the pathogenic mechanisms of metabolic abnormalities in major diseases. Our research focuses on several key areas:
1. Discovery and functional study of new types of protein modifications driven by metabolites, revealing new pathways by which metabolites regulate protein functions.
2. Exploration of new mechanisms by which metabolites regulate chromatin activity, thereby affecting gene expression and cellular fate.
3. Study of new mechanisms of metabolic enzymes in metabolic adaptation and regulation, further understanding the complex role of metabolic processes in cellular physiology and disease.
Through these research directions, we aim to uncover the intricate interplay between metabolism and cellular physiology and provide new perspectives and strategies for disease prevention and treatment.
Representative Peer-Reviewed Publications
(*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. Lysine L-lactylation is the dominant lactylation isomer induced by glycolysis. Nat Chem Biol. 2024 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.
(11) Zhang Y*, Zhang D*, Liang J, Yi X, Gui B, Yu W, Sun L, Yang X, Han X, Chen Z, Liu S, Si W, Yan R, Wang Y, Shang Y. (2016). Nucleation of DNA Repair Factors by FOXA1 Links DNA Demethylation to Transcriptional Pioneering. Nat Genet. 48(9): 1003-13.
Laboratory Introduction
