Personal Introduction

Dr Yeap received her Ph.D. degree from University of Cambridge in 2010 where she worked with Azim Surani on understanding the role of an epigenetic modifier, ESET, a histone H3K9 methyltransferase, in maintaining pluripotency of mouse embryonic stem cells. She did her postdoctoral training in the laboratory of Fred Alt at Harvard Medical School, Boston Children’s Hospital where she developed a new mouse model system and high throughput analysis to study antibody somatic hypermutation (SHM). She moved to Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine in 2016 as a Principal Investigator.

The research in the Yeap laboratory focuses on understanding the mechanisms of antibody diversification, specifically on how rare mutational outcomes from programmed DNA lesion processes in B cells contribute to anti-viral broadly neutralizing antibody (bnAb) activities or B cell-related diseases. Rare mutational outcomes on antibody genes such as insertion-deletions (indels), long complementarity determining region 3 (CDR3) and improbable mutations on certain nucleotides are bottlenecks that hinder the elicitation of bnAbs in vaccine strategies, resulting in the inefficiency of the immune system in fighting a fast evolving virus during a pandemic. They are interested in dissecting the genetic pathways that generate these rare mutational outcomes during Immunoglobulin (Ig) Somatic Hypermutation processes. Her lab has generated more than 40 mouse genetic models based on an in vivo hypermutating passenger-immunoglobulin B cell system and performed ultra-deep profiling of the mutational outcomes on the passenger-Ig gene to elucidate the pathways that generate the rare mutational outcomes and the effect of DNA sequences on mutation rate. Their ultimate aim is to generate humanized antibody mouse models based on their knowledge of antibody diversification processes to screen bnAbs and test vaccines. As the mutational outcomes during B cell receptor diversification processes also cause diseases such as autoimmune diseases and B cell cancers, they are also interested in collaborating with clinicians to identify the antibodies and antigens that resulted in these diseases.

Scientific Research Projects

• Funding Source: National Key Research and Development Project

Start-stop time: 12/31/2021-11/30/2026.

• Funding Source: National Key Research and Development Project

Start-stop time: 10/20/2020-12/31/2024.

• Funding Source: Excellent Young Scientist Fund, NSFC

Start-stop time: 1/1/2018-12/31/2020.

• Funding Source: NSFC-MAECI Chinese-Italian Collaborative Research Project

Start-stop time: 1/1/2018-12/31/2020.

• Funding Source: Shanghai Jiao Tong University

Start-stop time: 1, 2/1/2020-1/31/2021.

• Funding Source: General Program, NSFC

Start-stop time: 1/1/2017-12/31/2020.

Publications

1. Lei You#; Luning Zhang#; Shengqun Ouyang#; Bo Gao; Yanan Li; Jialu Li; Ningbo Wu; Hong Wang; Shiqi Sun; Jinfeng Li; Zi Yin; Ziyang Xu; Yao Chen; Yiwen Zhu; Shuangyan Zhang; Zhan Xu; Tianyu Zhang; Zhaoyuan Liu; Chuanxin Huang; Bin Li; Jieming Qu*; Bing Su*; Leng-Siew Yeap*; Multiple infections with omicron variants increase breadth and potency of omicron-specific neutralizing antibodies, Cell Discovery, 2025, 11(1):49.

2. Qian Hao; Jinfeng Li; Leng-Siew Yeap; Molecular mechanisms of DNA lesion and repair during antibody somatic hypermutation, Science China Life Sciences, 2024, 67(11):2344-2353.

3. Min Emma Huang#; Yining Qin#; Yafang Shang#; Qian Hao; Chuanzong Zhan; Chaoyang Lian; Simin Luo; Liu Daisy Liu; Senxin Zhang; Yu Zhang; Yang Wo; Niu Li; Shuheng Wu; Tuantuan Gui; Binbin Wang; Yifeng Luo; Yanni Cai; Xiaojing Liu; Ziye Xu; Pengfei Dai; Simiao Li; Liang Zhang; Junchao Dong; Jian Wang; Xiaoqi Zheng; Yingjie Xu; Yihua Sun; Wei Wu; Leng-Siew Yeap*; Fei-Long Meng*; C-to-G editing generates double-strand breaks causing deletion, transversion and translocation, Nature Cell Biology, 2024, 26(2):294-304.

4. Yanyan Wang; Fei-Long Meng*; Leng-Siew Yeap*; DNA flexibility can shape the preferential hypermutation of antibody genes, Trends in Immunology, 2024, 45(3): 167-176.

5. Yanyan Wang#; Senxin Zhang#; Xiaoqi Zheng; Leng-Siew Yeap*; Fei-Long Meng*; A    highthroughput protocol for deamination of long single-stranded DNA and oligo pools containing complex sequences, STAR Protocols, 2023, 4(4): 102602.

6. Yanyan Wang; Senxin Zhang; Xinrui Yang; Joyce K. Hwang; Chuanzong Zhan; Chaoyang Lian; Chong Wang; Tuantuan Gui; Binbin Wang; Xia Xie; Pengfei Dai; Lu Zhang; Ying Tian; Huizhi Zhang; Chong Han; Yanni Cai; Qian Hao; Xiaofei Ye; Xiaojing Liu; Jiaquan Liu; Zhiwei Cao; Shaohui Huang; Jie Song; Qiang Pan-Hammarström; Yaofeng Zhao; Frederick W. Alt; Xiaoqi Zheng; Lin-Tai Da; Leng-Siew Yeap*; Fei-Long Meng*; Mesoscale dna feature in antibody-coding sequence facilitates somatic hypermutation, Cell, 2023, 186(10): 2193-2207.e19.

7. Qian Hao#; Chuanzong Zhan#; Chaoyang Lian; Simin Luo; Wenyi Cao; Binbin Wang; Xia Xie; Xiaofei Ye; Tuantuan Gui; Claudia Voena; Chiara Pighi; Yanyan Wang; Ying Tian; Xin Wang; Pengfei Dai; Yanni Cai; Xiaojing Liu; Shengqun Ouyang; Shiqi Sun; Qianwen Hu; Jun Liu; Youqiong Ye; Jingkun Zhao; Aiguo Lu; Ji-Yang Wang; Chuanxin Huang; Bing Su; Fei-Long Meng; Roberto Chiarle*; Qiang Pan-Hammarström*; Leng-Siew Yeap*; DNA repair mechanisms that promote insertion-deletion events during immunoglobulin gene diversification, Science Immunology, 2023, 8(81): eade1167.

8. Bo Gao#; Liheng He#; Yujie Bao#; Yingying Chen#; Guanzhu Lu; Yu Zhang; Yingjie Xu; Bing Su; Jie Xu*; Ying Wang*; Leng-Siew Yeap*; Repeated vaccination of inactivated SARS-CoV-2 vaccine dampens neutralizing antibodies against Omicron variants in breakthrough infection, Cell Research, 2023, 33(3): 258-261.

9. Ying Tian#; Chaoyang Lian#; Yingying Chen#; Dong Wei; Xinxin Zhang; Yun Ling*; Ying Wang*; Leng-Siew Yeap*; Sensitivity and specificity of SARS-CoV-2 S1 subunit in COVID-19 serology assays, Cell Discovery, 2020, 6: 75-75.

10. Anqi Feng; Qian Hao*; Leng-Siew Yeap*; Contribution of rare mutational outcomes to broadly neutralizing antibodies, Acta Biochim Biophys Sin (Shanghai), 2022, 54(6): 820-827.

11. Leng-Siew Yeap*; Fei-Long Meng*; Cis- and trans-factors affecting AID targeting and mutagenic outcomes in antibody diversification, Advances in Immunology, 2019, 141, 51-103.

12. Liu Daisy Liu; Chaoyang Lian; Leng-Siew Yeap*; Fei-Long Meng*; The development of neutralizing antibodies against SARS-CoV-2 and their common features, Journal of Molecular Cell Biology, 2020, 12(12):  980-986.

13. Leng-Siew Yeap#; Joyce K Hwang#; Zhou Du; Robin M Meyers; Fei-Long Meng; Agne Jakubauskaite; Mengyuan Liu; Vinidhra Mani; Donna Neuberg; Thomas B Kepler; Jing H Wang; Frederick W Alt*; Sequence-intrinsic mechanisms that target AID mutational outcomes on antibody genes, Cell, 2015, 163(5): 1124-1137.

14. Joyce K Hwang; Chong Wang; Zhou Du; Robin M Meyers; Thomas B Kepler; Donna Neuberg; Peter D Kwong; John R Mascola; M Gordon Joyce; Mattia Bonsignori; Barton F Haynes; Leng-Siew Yeap*; Frederick W Alt*; Sequence intrinsic somatic mutation mechanisms contribute to affinity maturation of VRC01-class HIV-1 broadly neutralizing antibodies, Proceedings of the National Academy of Sciences of the United States of America, 2017, 114(32): 8614-8619.

15. Joyce K Hwang#; Frederick W Alt*; Leng-Siew Yeap#; Related mechanisms of antibody somatic hypermutation and class switch recombination, Microbiology Spectrum, 2015, 3(1): MDNA3-0037-2014.

16. Chiara Pighi; Qi Wang; Mara Compagno; Taek Chin Cheong; Fei Long Meng; Teresa Poggio; Leng-Siew Yeap; Elif Karaca; Rafael B Blasco; Fernanda Langellotto; Chiara Ambrogio; Claudia Voena; Adrian Wiestner; Siddha N Kasar; Jennifer R Brown; Jing Sun; Catherine J Wu; Monica Gostissa; Frederick W Alt*; Roberto Chiarle*; Phosphatidylinositol 3-kinase delta blockade increases genomic instability in B cells, Nature, 2017, 542(7642): 489-493.

17. Leng-Siew Yeap; Katsuhiko Hayashi; M Azim Surani; ERG-associated protein with SET domain (ESET)-Oct4 interaction regulates pluripotency and represses the rophectoderm lineage, Epigenetics and Chromatin, 2009, 2(1): 12-12.

18. Pengfei Dai#; Yuanqing Tan#; Yifeng Luo#; Tingting Liu; Yanchao Huang; Yafang Shang; Min Emma Huang; Xiaojing Liu; Senxin Zhang; Yanyan Wang; Qian-Xi Li; Niu Li; Lulu Li; Yining Qin; Junqi Liu; Liu Daisy Liu; Xia Xie; Yanni Cai; Fei Xavier Chen; Xiaoqi Zheng; Leng-Siew Yeap; Jian Wang*; Jinchuan Hu*; Fei-Long Meng*; Transcription-coupled AID deamination damage depends on ELOF1-associated RNA polymerase II, Molecular Cell, 2025, 85(7):1280-1295.e9.

19. Xiaoyi Zhou#; Jia Cong#; Rongguang Peng#; Dichen Yang#; Chenchen Dong; Jing Xie; Jiqi Yan; Jie Kuang; Fubin Li; Leng Siew Yeap; Xiaoyan Xie; Haolong Yin; Rulai Han; Liyun Shen; Yulin Zhou; Guang Ning*; Shu Wang*; Weiqing Wang*; Lei Ye*; Single-Cell RNA Sequencing of Thyroid Tissues Reveals Pathogenesis of Graves' Disease, Advanced Science (Weinh), 2025, e08449.

20. Xiaofei Ye; Weicheng Ren; Dongbing Liu; Xiaobo Li; Wei Li; Xianhuo Wang; Fei-Long Meng; Leng-Siew Yeap; Yong Hou; Shida Zhu; Rafael Casehs; Huilai Zhang*; Kui Wu*; Qiang Pan-Hammarstrom*; Genome-wide mutational signatures revealed distinct developmental paths for human B cell lymphomas, Journal of Experimental Medicine, 2021, 218(2): e20200573.

21. Xiaojing Liu; Tingting Liu; Yafang Shang; Pengfei Dai; Wubing Zhang; Brian J Lee; Min Huang; Dingpeng Yang; Qiu Wu; Liu Daisy Liu; Xiaoqi Zheng; Bo O Zhou; Junchao Dong; Leng-Siew Yeap; Jiazhi Hu; Tengfei Xiao; Shan Zha; Rafael Casellas; Liu X Shirley*; Feilong Meng*; ERCC6L2 promotes DNA orientation-specific recombination in mammalian cells, Cell Research, 2020, 30(9):732-744.

22. Dingpeng Yang; Ying Sun; Jingjing Chen; Ying Zhang; Shuangshuang Fan; Min Huang; Xia Xie; Yanni Cai; Yafang Shang; Tuantuan Gui; Liming Sun; Jiazhi Hu; Junchao Dong; Leng-Siew Yeap; Xiaoming Wang; Wei Xiao; Fei-Long Meng; REV7 is required for processing AID initiated DNA lesions in activated B cells, Nature Communications, 2020, 11(1): 2812.

23. Ke Lin; Yawen Zhou; Jingwen Ai; Yan A Wang; Senxin Zhang; Chao Qiu; Chaoyang Lian; Bo Gao; Tingting Liu; Hongyu Wang; Haocheng Zhang; Yi Zhang; Zhangfan Fu; Dan Li; Ning Jiang; Jingxin Guo; Jing Wu; Yan O Wang; Shusen Song; Qiang Li; Yanan Yin; Jia Xia 0, Yingjie Xu; Leng-Siew Yeap; Xiaoqi Zheng; Ye Gu; Hongyan Liu*; Wenhong Zhang*; Fei-Long Meng*; B cell receptor signatures associated with strong and poor SARS-CoV-2 vaccine responses, Emerging Microbes&Infections, 2022, 11 (1): 452-464.

24. Liu Daisy Liu; Min Huang; Pengfei Dai; Tingting Liu; Shuangshuang Fan; Xueqian Cheng; Yaofeng Zhao; Leng-Siew Yeap; Fei-Long Meng; Intrinsic Nucleotide Preference of Diversifying Base Editors Guides Antibody Ex Vivo Affinity Maturation, Cell Report, 2018, 25: 884-892.

25. Joon-Lin Chew; Yuin-Han Loh; Wensheng Zhang; Xi Chen; Wai-Leong Tam; Leng-Siew Yeap; Pin Li; Yen-Sin Ang; Bing Lim; Paul Robson; Huck-Hui Ng; Reciprocal transcription regulation of Pou5f1 and Sox2 via the Oct4/Sox2 complex in embryonic stem cells, Molecular and Cellular Biology, 2005, 25: 6031-6046.

Patent

• “Pluripotency associated epigenetic factor”, US patent publication number 20110190152, filed June 4, 2009, and issued August 4, 2011.