Professor Li-Sheng Zhang earned his Ph.D. in 2019 from The University of Chicago in Professor Chuan He lab, with the award of HHMI International Student Research Fellowship. During Ph.D. training, Li-Sheng discovered ALKBH7-mediated reversible RNA methylation in mitochondrial polycistronic RNA and demonstrated mRNA internal N⁷-methylguanosines via base-resolution sequencing. Li-Sheng continued working as a postdoctoral scholar in Professor Chuan He’s lab upon the completion of his Ph.D., where he developed the quantitative base-resolution sequencing strategy to investigate diverse RNA modifications in mammals, including BID-seq for pseudouridine, Nm-Mut-seq for 2′-O-methylation (Nm), DAMM-seq for m¹A/m³C/m¹G/m²₂G, m⁷G-seq/m⁷G-quant-seq for internal m⁷G, etc. In 2023 April, Li-Sheng joined HKUST and started his independent research in chemical biology, epigenetics, RNA biology, immunology, cancer biology, computational biology, and bioinformatics, as Assistant Professor in Life Science and Assistant Professor in Chemistry.

Research Question

Zhang Lab works on multiple research directions including (1) Quantitative base-resolution sequencing of messenger RNA (mRNA) modifications; (2) Reversible RNA methylation in gene expression regulation; (3) RNA-based therapeutics and RNA delivery; (4) Functional investigation of diverse RNA modifications in mRNA, chromosome-associated RNA (caRNA), non-coding RNA, mitochondrial RNA, and RNA virus; (5) Single-cell sequencing technology and bioinformatics; (6) Nanopore sequencing technology and bioinformatics; (7) Computational approaches of bioinformatics in deciphering the epitranscriptome; (8) Artificial intelligence in decoding epigenetic data. Zhang Lab aims to promote in-depth research with expertise in chemical biology, chemistry, genomics, genetics, immunology, RNA biology, cell biology, RNA biochemistry, nucleic acid chemistry, protein engineering, mass spectrometry, next-generation sequencing, bioinformatics, and machine learning to address fundamental questions related to gene expression regulation in diverse biological processes.

Representative Publications

(† These authors contributed equally; * Corresponding author.)

1. Zhang LS†, Dai Q†, He C*. Base-resolution sequencing methods for whole-transcriptome quantification of messenger RNA modifications. Accounts of Chemical Research 57, 47–58 (2024).
2. Zhang LS†, Ye C†, Ju CW†, Gao B, Feng X, Sun HL, Wei J, Yang F, Dai Q*, He C*. BID-seq for transcriptome-wide quantitative sequencing of mRNA pseudouridine at base resolution. Nature Protocols (2023) DOI: 10.1038/s41596-023-00917-5.
3. Chen L†, Zhang LS†, Ye C†, Zhou H, Liu B, Gao B, Deng Z, Zhao C*, He C*, Dickinson B*. Nm-Mut-seq: The base-resolution quantitative method for mapping transcriptome-wide 2’-O-methylations. Cell Research 33, 727–730 (2023).
4. Dai Q†^,*, Zhang LS†^,*, Sun H†, Pajdzik K†, Yang L, Ye C, Ju CW, Liu S, Wang Y, Zheng Z, Zhang L, Harada BT, Dou X, Irkliyenko I, Feng X, Pan T, He C*. Quantitative sequencing using BID-seq uncovers abundant pseudouridines in mammalian mRNA at base resolution. Nature Biotechnology 41, 344–354 (2023).
5. Feng X†, Cui X†, Zhang LS†, Ye C, Wang P, Zhong Y, Wu T, Zhong Z, He C*. Sequencing of N6-methyl-deoxyadenosine at single-base resolution across the mammalian genome. Molecular Cell (2024) DOI: 10.1016/j.molcel.2023.12.021.
6. Zhang LS, Xiong QP, Perez SP, Liu C, Wei J, Le C, Zhang L, Harada BT, Dai Q, Feng X, Hao Z, Wang Y, Dong X, Hu L, Wang ED, Pan T, Klungland A, Liu RJ*, He C*. ALKBH7-mediated demethylation regulates mitochondrial polycistronic RNA processing. Nature Cell Biology 23, 684–691 (2021).
7. Zhang LS*, Ju CW, Jiang B, He C. Base-resolution quantitative DAMM-seq for mapping RNA methylations in tRNA and mitochondrial polycistronic RNA. Methods in Enzymology 692, 39–54 (2023).
8. Zhang LS†, Liu C†, Ma H, Sun HL, Dai, Q, Luo G, Zhang Z, Zhang L, Hu L, Dong X, He C*. Transcriptome-wide mapping of internal N⁷-methylguanosine methylome in mammalian mRNA. Molecular Cell 74, 1304–1316 (2019).
9. Zhang LS†^,*, Ju CW†, Liu C†, Wei J, Dai Q, Chen L, Ye C, He C*. m⁷G-quant-seq: Quantitative Detection of RNA Internal N⁷-Methylguanosine. ACS Chemical Biology 17, 3306–3312 (2022).
10. Zhang LS, Dai Q, He C*. BID-seq: The Quantitative and Base-Resolution Sequencing Method for RNA Pseudouridine. ACS Chemical Biology 18, 4–6 (2023).
11. Zhang Y†, Zhang LS†, Dai Q, Chen P, Lu M, Kairis E, Murugaiah V, Xu J, Shukla R, Liang X, Zou Z, Cormet-Boyaka E, Qiu J, Peeples ME, Sharma A, He C*, Li J*. 5-methylcytosine (m⁵C) RNA modification controls the innate immune response to virus infection by regulating type I interferons. Proceedings of the National Academy of Sciences USA 119, e2123338119 (2022).
12. Shen S, Zhang LS*. The Regulation of Antiviral Innate Immunity through Non-m6A RNA Modifications.Frontiers in Immunology (2023) DOI: 10.3389/fimmu.2023.1286820.
13. Zhang LS, Chen G, Wang X, Guo QY, Zhang XS, Pan F, Chen K, Shi ZJ*. Direct borylation of primary C–H bonds in functionalized molecules by palladium catalysis. Angewandte Chemie International Edition 53, 3899–3903 (2014).
14. Zhang LS, Chen K, Chen G, Li BJ, Luo S, Shi ZJ*. Palladium-catalyzed trifluoromethylation of aromatic C–H bond directed by an acetamino group. Organic Letters 15, 10–13 (2013).
15. Hu L†^,*, Liu S†, Peng Y†, Ge R†, Su R†, Senevirathne C, Harada BT, Dai Q, Wei J, Zhang LS, Hao Z, Luo L, Wang H, Wang Y, Luo M, Chen M*, Chen J*, He C*. m6A RNA modifications are measured at single-base resolution across the mammalian transcriptome. Nature Biotechnology 40, 1210–1219 (2022).
16. He PC†, Wei J†, Dou X†, Harada B†, Zhang Z, Ge R, Liu C, Zhang LS, Yu X, Wang S, Lyu R, Zou Z, Chen M, He C*. Exon architecture controls mRNA m6A suppression and gene expression. Science 379, 677–682 (2023).