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胡家志

  

胡家志

 

电子邮件:hujz(at)pku(dot)edu(dot)cn;

 

研究方向:

基因组的稳定性关系到遗传物质的稳定传递以及细胞的正常增殖生长。 DNA双链的断裂极大地威胁基因组的稳定性,其能导致基因组的碱基突变、片段缺失、片段插入以及染色质的易位重组,从而在一定的程度上成为癌症细胞发生的来源。本实验室将结合分子生物学与高通量测序的方法来研究DNA双链断裂发生的机理,从而揭示癌症如何发生并进一步恶化的,并且通过这些方法来加速抗原特异性受体的筛选,从而实现病毒的防治和癌症的个体化治疗。具体研究方向为:细胞DNA复制过程中DNA双链产生的机理和后果;染色质易位的产生与癌症的发生过程;基因组3D结构变异产生的机理及其与癌细胞恶化的关系;人体疾病相关的特异性抗体的筛选与应用。

 

 

代表性科研论文: 

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.
Hu J#, Meyers RM#, Dong J, Panchakshari RA, Alt FW* & Frock RL*. (2015). 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.
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.
Frock RL#, Hu J#, & Alt FW. (2015). Mechanisms of recurrent chromosomal translocations. In book: Chromosomal Translocations and Genome Rearrangements in Cancer. Springer International Publishing, ISBN: 978-3-319-19983-2. doi: 10.1007/978-3-319-19983-2
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.
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.
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.
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.
 
其它科研论文(# co-first authors, *co-corresponding authors)
Zhao L#, Frock RL#, Du Z, Hu J, Cheng L, Krangel MS*, Alt FW*. (2016). Orientation-specific RAG activity in chromosomal loop domains contributes to Tcrd V(D)J recombination during T cell development. J Exp Med 213(9): 1921-36. doi: 10.1084/jem.20160670.
Dong J#, Panchakshari RA#, Zhang T#, Zhang Y, Hu J, Volpi SA, Meyers RM, Ho Y-J, Du Z, Robbiani DF, Meng F-L, Gostissa M, Nussenzweig MC, Manis JP*, & Alt FW*. (2015). Orientation-specific joining of AID-initiated DNA breaks promotes antibody class switching. Nature 525(7567): 134-9. doi: 10.1038/nature14970.

 

Meng F-L#, Du Z#, Federation A#, Hu J, Wang Q, Kieffer-Kwon KR, Meyers RM, Amor C, Wasserman CR, Neuberg D, Casellas R, Nussenzweig MC, Bradner JE*, Liu XS, & Alt FW*. (2014). Convergent transcription at intragenic Super-Enhancers targets AID-initiated genomic instability. Cell 159(7): 1538-48. doi: 10.1016/j.cell. 2014.11.014.
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