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
Honors and Awards
Peking University Boya Young Fellow, 2021
Bayer Investigator, 2021
Yi Fang Investigator, 2021
Epigenetic mechanisms including chromatin modifications, play essential gene regulatory roles in cell-type identity as well as in human diseases. It is becoming increasingly clear that there is a close link between nutrient state, energy metabolism and epigenetics. The classic examples are histone methylation and acetylation, which are derived from cellular metabolites S-adenosyl methionine and acetyl-CoA, respectively. Nevertheless, we know very little about whether there exist additional epigenetic pathways that use other metabolites as cofactors, and how cellular metabolites regulate gene function in general are largely unclear. Dr. Zhang first time identified histone lactylation and beta-hydroxybutyrylation, which are derived from lactate and ketone body accordingly. Dr. Zhang’s group are now interested in the molecular mechanisms mediating the crosstalk between metabolism and epigenetics. Using biochemistry, genetic, and multi-omics technology, we are focused to identify and study new types of chromatin modifications, new functions of metabolic enzymes, and how these mechanisms function in normal development, aging, and in human diseases including cancer, autoimmunity, etc.
Representative Peer-Reviewed Publications
1. 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. Class I histone deacetylases (HDAC1-3) are histone lysine delactylases. Sci Adv. 2022 Jan 21;8(3):eabi6696. doi: 10.1126/sciadv.abi6696. Epub 2022 Jan 19. PMID: 35044827; PMCID: PMC8769552.2. 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.
3. 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.
Nature news & views: https://www.nature.com/articles/d41586-019-03122-1
Science Signaling Editor’s choice: https://stke.sciencemag.org/content/12/606/eaba0502.full
Nature Immunology Research Highlight: https://www.nature.com/articles/s41590-019-0551-6
Trends in Biochemical Sciences Spotlight:https://www.sciencedirect.com/science/article/abs/pii/S0968000419302658
Immunity Preview: https://www.sciencedirect.com/science/article/pii/S1074761319304893
Nature reviews immunology Year in Review: MACROPHAGES IN 2019: https://www.nature.com/articles/s41577-019-0260-2
Nature reviews immunology Year in Review: INFLAMMATION IN 2019: https://www.nature.com/articles/s41577-019-0259-8
Nature reviews Cancer, Nature reviews immunology, Nature reviews Genetics, Nature reviews Microbiology, Nature reviews Endocrinology, Trends in biochemical Sciences, Trends in Cell Biology, Trends in Immunology
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. Li L, Shi L, Yang S, Yan R, Zhang D, Yang J, He L, Li W, Yi X, Sun L, Liang J, Cheng Z, Shi L, Yu W, Shang Y‡. (2016). SIRT7 Is a Histone Desuccinylase that Functionally Links to Chromatin Compaction and Genome Stability. Nat Commun. 7:12235.
Molecular Biology, for undergraduate students