The bacterial defense system has been engineered to be a versatile gene-editing system in mammals. However, the editing outcomes still require strict surveillance to ensure genome integrity during gene editing. We developed several tools to detect genome editing outcomes and also some new editing tools to improve the safety during genome editing. Next, we are planning to develop new genome editing tools based on the mammalian immune system.
Immunogenomics Laboratory
The immune system protects us from infection or diseases by effectively eliminating pathogens. Lymphocyte receptors, including the B cell receptor (secreted as an antibody) and T cell receptor, target B or T lymphocytes to pathogens and initiate the activation of the adaptive immune response. Lymphocyte receptors show high diversity upon generation and high specificity when recognizing antigens and thus become the most diverse system in humans. Immunogenomics refers to a new branch of molecular immunology that employs genomics methods to study the adaptive immune response based on lymphocyte receptors. Our major research interest is to develop and use genomics assays to investigate the mechanism underlying the diversification of lymphocyte receptors and uncover the two main mysteries in molecular immunology that are allelic exclusion and immune selection of lymphocytes. Lymphocytes protect us from disease, but genome instability can also convert normal lymphocytes to lymphomas or leukemia cells. Therefore, we also focus on how to maintain the genome integrity of lymphocytes.
Antibody Diversification
To study the regulatory mechanism of lymphocyte receptor diversity including RAG-mediated V(D)J recombination and AID-mediated class switch recombination and somatic hypermutation
Antibody Evolution
To develop sequencing-based screening systems to identify monoclonal antibodies and design a cell-based system for antibody generation, maturation, and evolution
Genome Integrity
To study how the DNA response and repair system deals with DNA breaks in the context of chromatin control to maintain the genome integrity of lymphocytes
Genome Editing
Safety assessment of current genome editing toolboxes and development of new editing tools based on the mammalian immune system
Genome Editing
Genomic Integrity
Lymphomas and leukemia are the main killer tumors for kids, largely due to the high genome instability of immune cells including lymphocytes. We focus on the generation of DNA damages, especially double-stranded breaks (DSBs), during the maturation of lymphocytes. The escape of DSBs generated during V(D)J recombination, class switch recombination, and somatic hypermutations may lead to severe chromosomal translocations that threaten genome integrity. Besides, DNA damages arising during the physiological activities of chromatin can also lead to tumorigenesis. Therefore, we are focusing on how cells sense and control the generation and repair of DNA damage.
Antibody Diversification
V(D)J recombination generates a highly diverse spectrum of antibody repertoire and class switch recombination plus somatic hypermutation further diversify antibody. We are developing high-throughput sequencing-based repertoire sequencing assays to trace the adaptive immune response to environment or pathogens, mainly focusing on the change of antibody or T cell receptors. These exploring will help us understand more about the development, maturation, and function of lymphocytes and also facilitate the identification of monoclonal antibodies against the antigen of interest.
Great Team
Our laboratory is well-established for self-motivated young scientists. We warmly welcome you to join us and build a positive, innovative, and active young team together. Our lab will make every effort to create opportunities for each participant to develop their talents and realize their aspirations.
Dr. Jiazhi Hu
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Dr. Yang Liu
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DR. Tingting Gan
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Jinchun Wu
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Changchang xin
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Yuefeng Guo
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Rusen Lu
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Yuhong Wang
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Lingyun Kong
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Xuhao Liu
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Zhengrong Zhangding
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Liqiong Ou
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Haoxin Liang
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Dr. Yang Liu
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DR. Tingting Gan
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Jinchun Wu
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Changchang xin
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Yuefeng Guo
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Rusen Lu
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Yuhong Wang
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Lingyun Kong
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Xuhao Liu
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Zhengrong Zhangding
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Selected Publications
Chromosomal loop domains direct the recombination of antigen receptor genes.
Hu J, Zhang Y, Zhao L, Frock RL, Du Z, Meyers RM, Meng FL, Schatz DG, Alt FW.Cell. Nov 5;163(4):947-59. doi: 10.1016/j.cell.2015.10.016.
PMID: 26593423
Genome-wide detection of DNA double-stranded breaks induced by engineered nucleases.
Frock RL, Hu J, Meyers RM, Ho YJ, Kii E, Alt FW.Nat Biotechnol. 2015 Feb;33(2):179-86. doi: 10.1038/nbt.3101.
PMID: 25503383