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Jiazhi Hu



Jiazhi Hu




Lab Homepage:https://hulab.pku.edu.cn/



Research Area:


The generation of diverse antigen receptors, including B and T cell receptors, relies on RAG-initiated V(D)J recombination. RAG generates DNA double-stranded breaks (DSBs) at antigen receptor loci during V(D)J recombination and these DSBs are repaired by classical non-homologue end joining (C-NHEJ) pathway. Few DSBs can escape from DNA repair and form chromosomal translocations that may induce over-expression of oncogenes (e.g. C-MYC, BCL-2) and lead to tumorigenesis. We developed new high throughput translocation / DSB sequencing methods and apply them to track the occurrence and repair of DSBs in vivo in order to study the mechanism of genomic stability maintenance. Our major interest is IMMUNOGRNOMICS and HUMAN DISEASES:

A. the safety assessment and improvement of genome editing tools;

B. DNA replication, transcription, and genome integrity during these DNA metabolism activities in lymphocytes;

C. the screening and engineering of antibody against disease-related antigens.


 Selected Publications:


1.     Yin J#, Liu M#, Liu Y#, Wu J, Gan T, Zhang W, Li Y, Zhou Y & Hu J (2019). Optimizing genome editing strategy by primer-extension-mediated sequencing. Cell Discovery 5, 819. doi: 10.1038/s41421-019-0088-8. 

2.     Zuo E#, Huo X#, Yao X#, Hu X#, Sun Y#, Yin J#, He B, Wang X, Shi L, Ping J, Wei Y, Ying W, Wei W, Liu W, Tang C, Li Y, Hu J* & Yang H*. (2017). CRISPR/Cas9-mediated targeted chromosome elimination. Genome Biology 18(1):224. doi: 10.1186/s13059-017-1354-4.

3.     Lin SG#, Ba Z#, Du Z#, Zhang Y, Hu J* & Alt FW*. (2016). A highly sensitive and unbiased approach for elucidating antibody repertoires. Proc Natl Acad Sci USA 113(28):7846-51. doi:10.1073/ pnas.1608649113.


4.     Hu J#, Meyers RM#, Dong J, Panchakshari RA, Alt FW* & Frock RL*. (2016). Detecting DNA double-stranded breaks in mammalian genomes by linear amplification-mediated high-throughput genome-wide translocation sequencing. Nature Protocols 11(5): 853-71. doi: 10.1038/nprot.2016.043.



5.     Hu J#, Zhang Y#, Zhao L, Frock RL, Du Z, Meyers RM, Meng F-L, Schatz DG, & Alt FW. (2015). Chromosomal loop domains direct the recombination of antigen receptor genes. Cell 163(4): 947-59. doi: 10.1016/j.cell.2015.10.016.



6.     Frock RL#, Hu J#, Meyers RM, Ho Y-J, Kii E, & Alt FW. (2015). Genome-wide detection of DNA double-stranded breaks induced by engineered nucleases. Nature Biotechnology 33(2):179-86. doi: 10.1038/nbt.3101.


7.     Hu J#, Tepsuporn S#, Meyers RM, Gostissa M*, & Alt FW*. (2014). Developmental propagation of V(D)J recombination-associated DNA breaks and translocations in mature B cells via dicentric chromosomes. Proc Natl Acad Sci USA 111(28): 10269-74. doi: 10.1073/pnas.1410112111.


8.     Tepsuporn S#, Hu J#, Gostissa M*, & Alt FW*. (2014). Mechanisms that can promote peripheral B-cell lymphoma in ATM-deficient mice. Cancer Immunol. Res. 2(9): 857-66. doi: 10.1158/2326-6066. CIR-14-0090.


9.     Hu J, Sun L, Shen F, Chen Y, Hua Y, Liu Y, Zhang M, Hu Y, Wang Q, Xu W, Sun F, Ji J, Murray JM, Carr AM, & Kong D. (2012). The intra-S phase checkpoint pathway targets Dna2 to prevent stalled replication forks from reversing. Cell 149(6): 1221-32. doi: 10.1016/j.cell.2012.04.030.


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