申请人一直从事B淋巴细胞抗体多样化及相关疾病研究，2015年回国建立独立实验室后重点研究抗体基因多样化机制及其关联疾病机理，迄今在Cell、EMBO J、Cell Res等期刊上发表（共同）第一作者研究论文6篇，撰写专著1章节。主要成果：发现抗体多样化过程中非编码RNA处理的蛋白质机器⎯RNA外切酶复合体的新功能；进而发现基因内超级增强子转录形成的对向转录招募胞苷去氨酶AID，阐释了B淋巴细胞癌变过程中DNA突变或断裂等基因组不稳定性的机制；利用基因组编辑工具构建了免疫缺陷等相关疾病小鼠模型。这些研究揭示了抗体多样化失调引起的免疫缺陷和基因组不稳定性中非编码RNA和DNA损伤修复因子的特殊重要功能，引领抗体多样化的前沿研究并开辟拓展了新的研究方向。今后将继续深入研究抗体多样化过程中非编码RNA、DNA损伤修复因子功能机制及失调引起的免疫缺陷等病理，旨为该类疾病的治疗提供新的靶点和思路。

This applicant studies the molecular mechanisms by which B cell diversify its antibody repertoire, and the molecular regulations of immunodeficiency and B cell genome integrity. Since 2008, this applicant had published 6 research papers in Cell, EMBO J, Cell Research, Cancer Immunology Research etc. as first or co-first author. This applicant also wrote the chapter 19 “The Mechanism of IgH Class Switch Recombination” as a major contributor in the book of “Molecular Biology of B cells” (2nd Edition). Amongst the publications, two papers that were published in Cell had made major contribution to the field of antibody diversification. This applicant found that the major non-coding RNA processing machine –RNA exosome is required for optimal class switch recombination and further identified that convergent transcription arised at intragenic super-enhancer regions can recruit Activation-induced cytidine deaminase to initiate somatic DNA mutation or strand breaks. Besides these achievements, the applicant had also successfully used CRISPR/Cas9 gene editing tools to generate mouse models of immunodeficiency and lymphomas. These results indicate that noncoding RNA and DNA repair factors could be key players in immunodeficiency and lymphomagenesis. This applicant proposes to focus on studies of these two categories of factors in the process of antibody diversification and study their roles in immunodeficiency diseases and lymphomas.