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.

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

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

Peking University Boya Young Fellow, 2021
Bayer Investigator, 2021
Yi Fang Investigator, 2021

2021-2025， Chinese Society of Biochemistry and Molecular Biology, Proteomics Division, Member

Cellular functions are intricately linked with metabolic processes, which not only serve as the source of cellular energy but also act as pivotal regulators of a wide range of physiological activities. Our research team is dedicated to uncovering the intricate mechanisms through which metabolism governs key physiological activities, thereby enabling cellular adaptation.

We employ a multi-faceted approach, integrating traditional biochemical, cellular, and molecular biology techniques with state-of-the-art omics technologies. This comprehensive methodology allows us to explore the nuances of metabolic regulation in depth. We have been at the forefront of identifying novel protein modifications catalyzed by cellular metabolites, including lysine lactylation (mediated by lactate) and lysine β-hydroxybutyrylation (mediated by ketone bodies).

Our current research is concentrated on three pivotal areas:

1. Discovery and Functional Analysis of Metabolite-Driven Protein Modifications: We are uncovering and studying new types of protein modifications, shedding light on previously unknown pathways through which metabolites modulate protein functions.
2. Regulation of Chromatin Activity by Metabolites: We are delving into the novel mechanisms by which metabolites influence chromatin activity, which in turn affects gene expression and ultimately, cellular fate.
3. Role of Metabolic Enzymes in Metabolic Adaptation and Regulation: We are examining new mechanisms involving metabolic enzymes in the context of metabolic adaptation and regulation, enhancing our understanding of the multifaceted role that metabolic processes play in cellular physiology and disease.

(*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. 34(2):91-92.
(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