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 lab upon the completion of his Ph.D., where he further expanded 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. Li-Sheng works on chemical biology, epigenetics, RNA biology, and bioinformatics.

Research Question

Zhang lab works on multiple areas in genetics and molecular biology, 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, RNA virus, etc.; (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, 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, 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).
2. 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).
3. 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).
4. 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).
5. 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).
6. 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).