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  • Name:Leng Siew Yeap

  • Office Location:Room 903, No. 5 Bldg., West Area, 280 South Chongqing Rd., Shanghai

  • Telephone:86-021-63846590-776726



2003 U. Msia Sabah B.Sc.

2010 Cambridge University Ph.D.


2003-2005 Genome Institute of Singapore     Research Assistant, Supervisor: Dr Bing Lim
2010-2015 Harvard Medical School, Boston Childrens Hospital, Howard Hughes Medical Institute     Postdoc, Supervisor: Dr Fred Alt
2016-current Shanghai Institute of Immunology, Shanghai Jiaotong University School of Medicine     Principal Investigator


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.                                                                                         



1.  Lin, K., Zhou, Y.W., Ai, J.W., Wang, Y.A., Zhang, S.X., Qiu, C., Lian, C.Y., Gao, B., Liu, T.T., Wang, H.Y., Zhang, H.C., Zhang, Y., Fu, Z.F., Li, D., Jiang, N., Guo, J.X., Wu, J., Wang, Y.O., Song, S.S., Li, Q., Yin, Y.A., Xia, J., Xu, Y.J., Yeap, L.S., Zheng, X.Q., Gu, Y., Liu, H.Y.*, Zhang, W.H.*,  Meng, F.L.*. B cell receptor signatures associated with strong and poor SARS-CoV-2 vaccine responses. Emerg Microbes Infect, 2022, 11 (1): 452-464.   [Link]

2.  Feng A.Q, Hao Q* and Yeap L.S.* (co-corresponding author). Contribution of rare mutational outcomes to broadly neutralizing antibodies. Acta Biochim Biophys Sin (Shanghai). 2022 May 25. Online ahead of print.   [Link]  

3.  Ye X.F., Ren W.C., Liu D.B., Li X.B., Li W., Wang X.H., Meng F.L., Yeap L.S., Hou Y., Zhu S.D., Casellas, R., Zhang H.L.*, Wu K.* and Pan-Hammarström Q. Genome-wide mutational signatures revealed distinct developmental paths for human B cell lymphomas. J Exp Med , 2021, 218(2): e20200573.   [Link]

4.  Liu L.D., Lian C.Y., Yeap, L.S.* (co-corresponding author) and Meng F.L.*. The development of neutralizing antibodies against SARS-CoV-2 and their common features. J Mol Cell Biol, 2020,12(12): 980-986.   [Link]

5.  Tian Y., Lian C.Y., Chen Y.Y., Wei D., Zhang X.X., Ling Y. *, Wang Y. * and Yeap L.S.* (co-corresponding author). Sensitivity and specificity of SARS-CoV-2 S1 subunit in COVID-19 serology assays. Cell Discov, 2020, 6(1): 75.   [Link]

6.  Liu, X.J., Liu TT, Shang, Y.F., Dai, P.F., Zhang, W.B.,  Lee, B.J., Huang, M., Yang D.P., Wu Q., Liu L.D., Zheng, X.Q., Zhou B.O., Dong, J.C., Yeap, L.S., Hu, J.Z., Xiao,T.F., Zha, S., Casellas, R., Liu, X.S.* and Meng, F.L.*. ERCC6L2 promotes DNA orientation-specific recombination in mammalian cells. Cell Res, 2020, 30(9): 732-744.   [Link]

7.  Yang, D.P., Sun, Y., Chen, J.J., Zhang, Y., Fan, S.S., Huang, M., Xie, X., Cai, Y.N., Shang, Y.F., Gui, T.T., Sun, L.M., Hu, J.Z., Dong, J.C., Yeap, L.S., Wang, X.M., Xiao, W. and Meng, F.L.*. REV7 is required for processing AID initiated DNA lesions in activated B cells. Nat Commun, 2020, 11(1): 2812.   [Link]

8.  Yeap,L.S.* (co-corresponding author) and Meng F.L.*. Cis- and trans-factors affecting AID targeting and mutagenic outcomes in antibody diversification. Adv Immunol, 2019, 141: 51-103..   [Link]

9.  Liu, L.D., Huang M., Dai P., Liu T., Fan S., Cheng X., Zhao Y., Yeap, L.S. and Meng F.L. Intrinsic Nucleotide Preference of Diversifying Base Editors Guides Antibody Ex Vivo Affinity Maturation. Cell Report, 2018, 25: 884-892.   [Link]

10.  Hwang, J.K., Wang C., Du Z., Meyers R.M., Kepler T.B., Neuberg D., Kwong P.D., Mascola J.R., Gordon Joyce M., Bonsignori M., Haynes B.F., Yeap L.S.* (co-senior author) and Alt F.W.* . Sequence intrinsic somatic mutation mechanisms contribute to affinity maturation of VRC01-class HIV-1 broadly neutralizing antibodies. PNAS, 2017, 1-6.   [Link]

11.  Campagno, C., Wang Q., Pighi C., Cheong T.C., Meng F.L., Poggio T., Yeap L.S., Atabay E., Blasco R.B., Langellotto F., Voena C., Kasar S.N., Brown J.R., Sun J., Wu C.J., Gostissa M., Alt F.W and Chiarle R . Phosphatidylinositol 3-kinase δ blockade increases genomic instability in B cells. Nature, 2017, 542(7642): 489-493.   [Link]

12.  Yeap, L.S.# (co-first author), Hwang J.K.#, Du Z., Meyers R.M., Meng F.L., Jakubauskaite, A., Liu M., Mani V., Neuberg D., Kepler T.B., Wang, J.H. and Alt F.W. 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):1055-1056.   [Link]

13.  Hwang, J.K.#, Alt F.W. and Yeap L.S.# (equal contribution). Related Mechanisms of Antibody Somatic Hypermutation and Class Switch Recombination. Microbiol Spectr, 2015, 3(1): MDNA3-0037-2014.   [Link]

14.  Yeap, L.S. (first author), Hayashi K. and Surani M.A. ERG-associated protein with SET domain (ESET)-Oct4 interaction regulates pluripotency and represses the trophectoderm lineage. Epigenetics Chromatin , 2009, 2: 12.   [Link]

15.  Chew, J.L, Loh Y.H., Zhang W., Chen X., Tam W.L., Yeap L.S., Li P., Ang Y.S., Lim B., Robson P. and Ng H.H. Reciprocal transcription regulation of Pou5f1 and Sox2 via the Oct4/Sox2 complex in embryonic stem cells. Mol. Cell. Biol, 2005, 25: 6031-6046.   [Link]


Qian Hao,Ph.D.

Assistant Research Fellow

Bo Gao,Ph.D.

Postdoctoral Research Fellow


Shengqun Ouyang,M.S




Chaoyang Lian

Ph.D. Candidate (Class 2019)



Zi Yin

M.S Candidate (Class 2020)



Wenyi Cao

Ph.D. Candidate (Class 2020)



Jinfeng Li

Ph.D. Candidate (Class 2021)




Chuanzong Zhan

Ph.D. Candidate (Class 2018, Graduated)





Simin Luo

M.S Candidate (Class 2019, Graduated)


Lab Location:Room 901, No. 5 Bldg., West Area, 280 South Chongqing Rd., Shanghai




Copyright 2016. Shanghai Institute of Immunology,Shanghai Jiao Tong University School of Medicine.All Rights Reserved.