研究方向
有颌脊椎动物的免疫系统可以有效地抵御病原体的入侵并清除自身的异常细胞,包括癌细胞。其中,适应性免疫系统的淋巴细胞可以产生多样性的抗原受体而特异性识别病原体和异常细胞。淋巴细胞受体包括B细胞受体和T细胞受体,前者的分泌形式即抗体。淋巴细胞介导的获得性免疫在疾病治疗方面具有巨大的应用价值,如单克隆抗体相关药物在肿瘤治疗方面取得了显著成效。本课题组的研究方向集中在免疫基因组学与人类疾病。我们开发了一系列基因组学测序方法用于免疫学方向的研究,可以用于基因编辑工具(以基于细菌免疫系统的CRISPR/Cas为主)的评估、基因组稳定性的检测以及抗体和T细胞受体的测序。我们的研究方向主要集中在:基因编辑工具的安全性评估及改进、淋巴细胞的复制与转录及其基因组稳定性维持机制、疾病抗原的特异性抗体筛选及改造。
代表性科研论文
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, C hen 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.