研究方向：适应性免疫是免疫系统的重要组成部分，可特异有效地清除逃过天然免疫的抗原，维持机体健康。B细胞生成的多样性抗体是适应性免疫的重要基础，主要来源于RAG蛋白介导免疫球蛋白基因的V(D)J重排；AID蛋白介导抗体基因类型转换重排(CSR)和V(D)J外显子超频突变(SHM)。RAG和AID蛋白介导起始的重排突变过程能促进生理状态下多样性抗体的生成，同时其脱靶效应严重威胁基因组稳定性，诱发免疫异常及基因组不稳定相关疾病。抗体生成多样性的研究对于认识机体自身免疫系统发育、免疫异常相关疾病发生干预、疫苗和抗体类药物开发均具有重要意义。课题组将结合基因编辑，高通量测序等技术系统地研究抗体成熟及其多样性，染色质三维结构及其动态调控基因组稳定性的机制，并阐释免疫缺陷和基因组稳定性异常相关疾病的发病机制并提供潜在的干预治疗策略。
代表性科研论文：
1. Luo S, Qiao R, Zhang X*. DNA damage response and repair in adaptive immunity. Front Cell Dev Biol. 2022, 10:884873. Invited review.
2. Zhang Y, Zhang X, Dai H-Q, Hu H, Alt FW. The role of chromatin loop extrusion in antibody diversification. Nat Rev Immunol. 2022, 22(9):550-556. Invited review.
3. Zhang X*, Yoon HS, Chapdelaine-Williams AM, Kyritsis N, Alt FW*. Physiological role of the 3’IgH CBEs super anchor in antibody class switching Proc Natl Acad Sci U S A. 2021, 118(3):e2024392118. (* Co-corresponding author)
Commented by: Proc Natl Acad Sci U S A. 2021, 118(6):e2026399118.
4. Zhang X, Zhang Y, Ba Z, Kyritsis N, Casellas R, Alt FW*. Fundamental roles of chromatin loop extrusion in antibody class switching. Nature. 2019, 575(7782):385-389.
Commented by: Nature. 2019, 575(7782):291-293.
5. Zhang Y#, Zhang X#, Ba Z, Liang Z, Dring EW, Hu H, Lou J, Kyritsis N, Zurita J, Shamim MS, Presser Aiden A, Lieberman Aiden E, Alt FW*. The fundamental role of chromatin loop extrusion in physiological V(D)J recombination. Nature. 2019 573(7775):600-604. (# Co-first author)
Commented by: Nature. 2019, 575(7782):291-293. Immunol Cell Bio. 2019. 97:859-861.
6. Panchakshari RA#, Zhang X#, Kumar V, Du Z, Wei PC, Kao J, Dong J*, Alt FW*. DNA double-strand break response factors influence end-joining features of IgH class switch and general translocation. Proc Natl Acad Sci U S A. 2018, 115(4):762-767. (# Co-first author)
