Name: Leng Siew Yeap

Title： Principal investigator

Email: yeaplengsiew@shsmu.edu.cn

Tel: 021-63846590*776726

Research Interests

Mechanisms of Broadly Neutralizing Antibody Generation

The long term goals of the lab are to elucidate mechanism that generate potent neutralizing antibodies and to establish approaches using such antibodies to fight pathogens and diseases. Specifically, we study the mechanisms of Somatic Hypermutation (SHM), a process whereby point mutations and sometimes insertions and deletions (indels) are introduced in the antibody variable region genes for increase binding affinity of the B cells with antigens. SHM is mediated by a DNA mutator, activation induced cytidine deaminase (AID). While the activities of AID at the immunoglobulin (Ig) genes are important for achieving high-affinity neutralizing antibodies, its off-target activities at non-Ig genes could be disastrous (reviewed in Yeap and Meng, Adv Immunol., 2019). For example, AID targeting at oncogenes such as c-myc and Bcl6 may result in translocation and juxtaposition of the Ig enhancer next to the oncogenes, a hallmark in B cell cancer. Thus, the study of the mechanisms of AID targeting is important in understanding immunity and prevention of cancer.                                                                      

Our lab is particularly interested in studying the mechanisms that generate anti-viral broadly neutralizing antibodies (bnAbs) especially those that are rare and takes a long time to generate such as anti-HIV bnAbs. Such anti-HIV bnAbs have common characteristics such as frequent insertion and deletion in the antibody genes, long CDR3, high frequency of point mutations and are often poly/autoreactive. Our aims are to understand how these special features of the bnAbs are generated during the process of SHM and ultimately apply the knowledge learnt to speed up the process that generate bnAbs. Our long term goal is to establish approaches to efficiently fight diseases and prevent cancer.

Ten Selected Papers

*co-corresponding authors; #co-first authors

1. Liu Daisy Liu, Chaoyang Lian, Leng-Siew Yeap*, Fei-Long Meng*. The development of neutralizing antibodies against SARS-CoV-2 and their common features. J Mol Cell Biol, 2021, 12(12): 980-986.

2. 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 Discov, 2020, 6(1): 75.

3. 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, X. Shirley Liu*, Fei-Long Meng*. ERCC6L2 promotes DNA orientation-specific recombination in mammalian cells. Cell Res, 2020, 30(9): 732-744.

4. Yeap, LS*, Meng FL*. Cis- and trans-factors affecting AID targeting and mutagenic outcomes in antibody diversification. Adv Immunol, 2019, 141: 51-103.

5. 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.

6. 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. PNAS, 2017, 114(32): 8614-8619.

7. Mara Compagno#, Qi Wang#, Chiara Pighi#, 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 δ blockade increases genomic instability in B cells. Nature, 2017, 542(7642): 489-493.

8. Leng-Siew Yeap#, Joyce K. Hwang#, Zhou Du, Robin M. Meyers, Fei-Long Meng, Agnė Jakubauskaitė, 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. Featured in Preview by Cornelis Murre, Cell, 163(5): 1124-1137.

9. Joyce K. Hwang#, Leng-Siew Yeap#, Frederick W. Alt*. Related Mechanisms of antibody somatic hypermutation and class switch recombination. Microbiol Spectr, 2015, 3(1): MDNA3-0037-2014.

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