Jiazhi Hu, Ph.D.
Genome dynamics and immune cell function research group
Professor, College of Life Sciences, Peking University
tel：
E-mail：hujz@pku.edu.cn
1. Investigating the interplay between DNA replication, DNA damage, and other DNA metabolic activities with genome stability and tumorigenesis in the complex chromatin environments of mammals;
2. Exploring the spatiotemporal dynamics of the aging process or functional changes in lymphocyte activity across different tissues, along with the associated alterations in DNA metabolism;
3. Focusing on the mechanisms underlying antibody development and maturation, and utilizing synthetic biology techniques to engineer cells for efficient antibody development and evolution.
DNA replication: the team has elucidated the mechanism by which eukaryotic cells stabilize stalled DNA replication forks (Cell 2012), proposed the "transcription bulldozer" model for the regulation of DNA replication initiation by transcription in mammalian cells (Genome Biology 2021), and explained the mechanism by which the Cohesin complex, which maintains the three-dimensional structure of chromatin, orderly regulates the timing of DNA replication to maintain genome stability (Nature Genetics 2023). They have also discovered the persistent coupling phenomenon of sister replication forks during mammalian replication and proposed a pre-determination model for the early determination of DNA replication termination (Science 2024), pioneering a new field of research on DNA replication within complex chromatin environments.
DNA repair: The team has elucidated the mechanism by which the key DNA break repair protein ATM inhibits the development of B-cell lymphoma (PNAS 2014; Cancer Research Immunology 2014), comprehensively identified the DNA repair products generated during gene editing, and developed a rationally designed Cas9 variant, Cas9TX, which can effectively reduce deleterious byproducts of in vivo gene editing (Nature Biotechnology 2015; Cell Discovery 2019; STAR Protocols 2021; Nucleic Acids Research 2021a, b, 2022; Nature Communications 2022a, b, c, 2024).
DNA Recombination: the team has proposed a tracking and scanning model for the RAG enzyme during antibody V(D)J rearrangement (Cell 2015), and revealed the critical role of membraneless organelles in protecting lymphocyte genome stability (Cell Reports 2021, EMBO Journal 2022). The team has also developed a high-sensitivity antibody repertoire sequencing method based on genomic DNA (PNAS 2016), and has applied for a patent for the PEM-seq method, which comprehensively detects gene products, promising to become the standard for safety testing in gene editing therapies.
Liu Y, Zhangding Z, Liu X, Gan T, Ai C, Wu J, Liang H, Chen M, Guo Y, Lu R, Jiang Y, Ji X, Gao N, Kong DC, Li Q, Hu JZ. (2024) Fork coupling directs DNA replication elongation and termination. Science, 338: 1215-22.
Wu J, Liu Y, Zhangding Z, Liu X, Ai C, Gan T, Liang H, Guo Y, Chen M, Liu Y, Yin J, Zhang W, Hu JZ. (2023) Cohesin maintains replication timing to suppress DNA damage on cancer genes. Nat. Genet., 55: 1347-1358.
Yin J, Fang K, Gao Y, Ou L, Yuan S, Xin C, Wu W, Wu WW, Hong J, Yang H , Hu JZ. (2022) Safeguarding genome integrity during gene-editing therapy of age-related macular degeneration. Nat. Commun., 13: 7867.
Wu J, Zou ZY, Liu Y,, Liu X, Zhangding Z, Xu M , Hu JZ. (2022) CRISPR/Cas9-induced structural variations expand in T lymphocytes in vivo. Nucl. Acids Res, 50: 11128-11137.
Xin C, Yin J, Yuan S, Ou L, Liu M, Zhang W , Hu JZ. (2022) Comprehensive assessment of miniature CRISPR-Cas12f nucleases for gene disruption. Nat. Commun., 13: 5623.
Xie X, Gan T, Rao B, Zhang W, Panchakshari RA, Yang D, Ji X, Cao Y, Alt FW, Meng FL, Hu JZ. (2022) C-terminal deletion-induced condensation sequesters AID from IgH targets in immunodeficiency. EMBO J., 41: e109324.
Yin J, Lu R, Xin C, Wang Y, Ling X, Li D, Zhang W, Liu M, Xie W, Kong L, Si W, Wei P, Xiao B, Lee HY, Liu T , Hu JZ. (2022) Cas9 exo-endonuclease eliminates chromosomal translocations during genome editing. Nat. Commun., 13: 1204.
Gan T, Wang Y, Schatz DG, Hu JZ. (2021) RAG2 abolishes RAG1 aggregation to facilitate V(D)J recombination. Cell Rep., 37: 209824.
Liu M, Zhang W, Xin C, Yin J, Shang Y, Ai C, Li J, Meng FL , Hu JZ. (2021) Global detection of DNA repair outcomes induced by CRISPR-Cas9. Nucl. Acids Res., 49: 8732-8742.
Zhang W, Yin J,, Zhang-Ding Z, Xin C, Liu M, Wang Y, Ai C, Hu JZ. (2021) In-depth assessment of the PAM compatibility and editing activities of Cas9 variants. Nucl. Acids Res., 49: 8785-8795.
Liu Y, Ai C, Gan T, Wu J, Jiang Y, Liu X, Lu R, Gao N, Li Q, Ji X, Hu JZ. (2021) Transcription shapes DNA replication initiation to preserve genome integrity. Genome Biol., 22: 176.
Yuhong Wang, Xuhao Liu, Zhengrong Zhangding, Haoxin Liang, Xinyi Liu, Wanlin Chen, Wanqin Rao, Jiayi Chen, Ruiqi Pi, Qiuyu Lu
