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

2. Liu L.D., Lian C.Y., Yeap, L.S.*（叶菱秀，共同通讯作者） 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.

3. Tian Y., Lian C.Y., Chen Y.Y., Wei D., Zhang X.X., Ling Y. *, Wang Y. *, Yeap L.S.* (叶菱秀，共同通讯作者). Sensitivity and specificity of SARS-CoV-2 S1 subunit in COVID-19 serology assays. Cell Discov, 2020, 27(6): 75.

4. 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.（叶菱秀）, 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.

5. 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.（叶菱秀）, 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.

6. Yeap, L.S.* (叶菱秀，共同通讯作者）and Meng F.L.*. Cis- and trans-factors affecting AID targeting and mutagenic outcomes in antibody diversification. Adv Immunol, 2019, 141: 51-103.

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

8. 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.*(叶菱秀，共同通讯作者） 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.

9. Campagno, C., Wang Q., Pighi C., Cheong T.C., Meng F.L., Poggio T., Yeap L.S. （叶菱秀）, 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.

10. Yeap, L.S.# (叶菱秀, 共同第一作者）, 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): 1124-37. *co-first authors. Featured in Preview by Cornelis Murre, Cell 163(5):1055-1056.

11. Hwang, J.K.#, Alt F.W. and Yeap L.S#（叶菱秀，共同第一作者） . Related Mechanisms of Antibody Somatic Hypermutation and Class Switch Recombination. Microbiol Spectr, 2015, 3(1):MDNA3-0037-2014. doi:10.1128/microbiolspec.MDNA3-0037-2014.

12. Yeap, L.S. （叶菱秀，第一作者）, 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.

13. Chew, J.L, Loh Y.H., Zhang W., Chen X., Tam W.L., Yeap L.S.（叶菱秀）, 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.

Patent

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