2005 – 2010, Ph.D. in Chemical Biology, University of Chicago
2001 – 2005, B.S. in Chemistry, University of Science and Technology of China
2019 – present, Professor, School of Life Sciences, Peking University
2012 – 2018, Assistant, Associate & Full Professor, School of Life Sciences, Peking University
2014 – present, adjunct principle investigator, College of Chemistry and Molecular Engineering, Peking University
2013 – present, Principle Investigator, Synthetic and Functional Biomolecules Center (SFBC), Peking University
2012 – present, Principle Investigator, Center for Life Sciences
2010 – 2011, Postdoctoral fellow in Biochemistry & Molecular Biology, University of Chicago
Honors and Awards
Leading talents of ten thousands plan of the Central Organization Department, 2019
The National Science Fund for Outstanding Young Scholars, 2018
National ten thousands plan program-leading talents in science and technology Innovation, 2018
The 16th Henry Fok Ying Tung Young Teachers Fund, 2018
OKeanos-CAPA Young Investigator Award, 2018
Bayer Investigator at PKU, 2018
Chinese Chemical Society Chemical Biology Award, 2018
The 10th `Yaoming Kangde Life Chemistry Research Award` scholar award, 2016
Chinese Chemical Society Youth Chemistry Award,2016
The National Science Fund for Distinguished Young Scholars, 2016
IUPAC Prize for Young Chemists, International Union of Pure and Applied Chemistry, 2011
Professional Society Affiliations
2017 - present, the Chinese Cell Biology Society
2013 – present, the RNA society
2013 – present, the Chinese Society of Biochemistry and Molecular Biology
2012 – present, the Chinese Crystallographic Society
2012 – present, the Chinese Chemical Society
We probe the pathways and mechanisms of DNA/RNA modification，de-modification and the development of new methods of gene editing. In order to do so, we integrate multiple disciplines including chemical biology, epigenetics, nucleic acid chemistry, cell biology, biochemistry,and structural biology. An ultimate goal is to uncover new functions and regulatory mechanisms of the epigenetic DNA/RNA modifications.
1. RNA Modifications and EpitranscrIptomics
More than 100 distinct post-transcrIptional modifications have been characterized so far; they were considered to be static and unalterable after covalent installation. Recent discoveries of reversible RNA methylation in the form of N6-methyladenosine (m6A) have demonstrated RNA modification-mediated regulation of gene expression, leading to the emerging field of “epitranscrIptomics”.
In addition to m6A, there are other epitranscrIptomic marks. My laboratory recently discovered that pseudouridine (Ψ) and N1-methyladenosine (m1A), two post-transcrIptional modifications in non-coding RNAs, are also present in mammalian mRNAs. My laboratory showed that these epitranscrIptomic marks are prevalent in mRNA, dynamically-regulated by various stimuli and reversible by potential “eraser” proteins in the case of m1A. However, the biological consequences of mRNA pseudouridylation and m1A methylation are unknown. Utilizing epitranscrIptome sequencing tools we have developed, we hope to elucidate the functional consequences and regulatory mechanisms of these RNA modifications, hence leading to new territories in the nascent field of epitranscrIptomics.
2. Genome-editing Tools
Genome-editing technologies have emerged as powerful tools for basic biology and medicine. Based on our expertise in chemical biology, molecular biology and high-throughput sequencing, we evaluate existing genome-editing tools as well as develop next-generation genome-editing technologies.
3. TET- and TDG-dependent Active DNA Demethylation
The ten-eleven translocation (TET)-dependent generation and removal of oxidized derivatives of 5-methylcytosine (5mC), namely 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC), uncovered a new paradigm of active DNA demethylation in mammalian genomes. Besides acting as demethylation intermediates, these oxidized variants of 5mC may also play functional roles. Emerging evidence has suggested 5hmC as a stable epigenetic modification implicated in many biological processes and various diseases. 5fC and 5caC, further oxidation products of 5hmC, accumulate at distal regulatory elements as active DNA demethylation intermediates and can be removed through base excision repair by mammalian thymine DNA glycosylase (TDG). My laboratory recently developed “fC-CET”, a bisulfite-free, base-resolution method for the genome-wide identification of 5fC sites. We will continue to develop robust and sensitive sequencing technologies, including those applicable to single-cell studies and clinical investigations, to dissect the functional roles of these epigenetic DNA modifications.
Representative Peer-Reviewed Publications
1. Song J, Dong L, Sun H, Luo N, Huang Q, Li K, Shen X, Jiang Z, Lv Z, Peng L, Zhang M, Wang K, Liu K, Hong J, Yi C. CRISPR-free, programmable RNA pseudouridylation to suppress premature termination codons. Molecular Cell, 2023, 83, 139-155.
2. Liu C, Sun H, Yi Y, Shen W, Li K, Xiao Y, Li F, Li Y, Hou Y, Lu B, Liu W, Meng H, Peng J, Yi C *, Wang J.* Absolute quantification of single-base m6A methylation in the mammalian transcriptome using GLORI. Nat Biotechnol. 2023,41,355-366.
3. Zhang M, Jiang Z, Ma Y, Liu W, Zhuang Y, Lu B, Li K, Peng J, Yi C*. Quantitative profiling of pseudouridylation landscape in the human transcriptome. Nat Chem Biol. 2023 Mar 30. doi: 10.1038/s41589-023-01304-7.
4. Lei Z, Meng H, Liu L, Zhao H, Rao X, Yan Y, Wu H, Liu M, He A,Yi, C*. Mitochondrial base editor induces substantial nuclear off-target mutations. Nature. 2022,606, 804–811
5. Chen L, Zhu B, Ru G, Meng H, Yan Y, Hong M, Zhang D., Luan C, Zhang S., Wu H., Gao H, Bai S, Li C, Ding R, Xue N, Lei Z, Chen Y, Guan Y, Siwko S, Cheng Y, Song G, Wang L, Yi C*, Liu M*, Li D* Re-engineering the adenine deaminase TadA-8e for efficient and specific CRISPR-based cytosine base editing. Nat Biotechnol. 2022, Nov 10. doi: 10.1038/s41587-022-01532-7
6. Zhuang Y, Liu J, Wu H, Zhu Q, Yan Y, Meng H, Chen PR, Yi C*. Increasing the efficiency and precision of prime editing with guide RNA pairs. Nat Chem Biol. 2022; 18:29-37.
7. Lei Z, Meng H, Lv Z, Liu M, Zhao H, Wu H, Zhang X, Liu L, Zhuang Y, Yin K, Yan Y, Yi C.* Detect-seq reveals out-of-protospacer editing and target-strand editing by cytosine base editors. Nat Methods. 2021; 18:643-651.
8. Cui Q, Yin K, Zhang X, Ye P, Chen X, Chao J, Meng H, Wei J, Roeth D, Li L, Qin Y, Sun G, Zhang M, Klein J, Huynhle M, Wang C, Zhang L, Badie B, Kalkum M, He C, Yi C* and Shi Y*. Targeting PUS7 suppresses tRNA pseudouridylation and glioblastoma tumorigenesis. Nat Cancer.2021; 2:932–949.
9. Liu J, Li K, Cai J, Zhang M, Zhang X, Xiong X, Meng H, Xu X, Huang Z, Peng J. Fan J*, YI C*. Landscape and Regulation of m6A and m6Am Methylome across Human and Mouse Tissues. Mol Cell. 2020; 77:426-440.
10. Song J, Zhuang Y, Zhu C, Meng H, Lu B, Xie B, Peng J, Li M*, Yi C*. Differential roles of human PUS10 in miRNA processing and tRNA pseudouridylation. Nat Chem Biol. 2020; 16: 160-169.
We probe the pathways and mechanisms of RNA/DNA
modification. In order to do so, we integrate multiple
disciplines including chemical biology, epigenetics, RNA modifications, genome editing, single-cell omics and genomics tools. An ultimate goal
is to uncover new functions and regulatory mechanisms of the epigenetic RNA/DNA
modifications, with an emphasis on RNA biology to impact disease diagnoses and thearpy.