研究組長介紹
姓名：Leng Siew Yeap
電話：021-63846590*776726
郵箱：[email protected]
個(gè)人簡歷
2000-2003 馬來西亞沙巴大學(xué) 學(xué)士
2003-2005 新加坡基因組研究所 研究助理 導(dǎo)師: Bing Lim教授
2005-2010 劍橋大學(xué) 博士 導(dǎo)師: Azim Surani教授,，表觀遺傳與干細(xì)胞
2010-2015 哈佛大學(xué) 博士后 導(dǎo)師: Frederick W. Alt教授
2016-至今 上海交通大學(xué)醫(yī)學(xué)院上海市免疫學(xué)研究所 研究員,，課題組長
研究方向
Mechanisms of Broadly Neutralizing Antibody Generation
The long term goals of the lab are to elucidate mechanism that generates 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.
科研項(xiàng)目
1）項(xiàng)目類型：科技部國家重點(diǎn)研發(fā)計(jì)劃子課題
起止年月：2020.10-2024.12
2）項(xiàng)目類型：上海交通大學(xué)“ 交大之星” 計(jì)劃醫(yī)工交叉研究基金
起止年月：2020.02-2021.01
3）項(xiàng)目類型：國家自然科學(xué)基金優(yōu)秀青年基金
起止年月：2018.01-2020.12
4）項(xiàng)目類型：國家自然科學(xué)基金國際合作項(xiàng)目
起止年月：2018.01-2020.12
5）項(xiàng)目類型：國家自然科學(xué)基金面上項(xiàng)目
起止年月：2017.01-2020.12
論文與專著
1. Ye X.F., Ren W.C., Liu D.B., Li X.B., Li W., Wang X.H., Meng F.L., Yeap L.S.(葉菱秀), 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. Tian Y., Lian C.Y., Chen Y.Y., Wei D., Zhang X.X., Ling Y. *, Wang Y. *, Yeap L.S.* (葉菱秀，共同通訊作者). Sensitivity and specificity of SARS-CoV-2 S1 subunit in COVID-19 serology assays. Cell Discov, 2020, 27(6): 75.
3. 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. (葉菱秀), 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.
4. 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. (葉菱秀), Wang, X.M., Xiao, W., Meng, F.L. REV7 is required for processing AID initiated DNA lesions in activated B cells. Nat Commun, 2020, 11(1): 2812.
5. Yeap, L.S.* (葉菱秀,，共同通訊作者) and Meng F.L.*. Cis- and trans-factors affecting AID targeting and mutagenic outcomes in antibody diversification. Advances in Immunology, 2019, 141: 51-103.
6. Liu, L.D., Huang M., Dai P., Liu T., Fan S., Cheng X., Zhao Y., Yeap, L.S (葉菱秀) and Meng F.L. Intrinsic Nucleotide Preference of Diversifying Base Editors Guides Antibody Ex Vivo Affinity Maturation. Cell Report, 2018, 25: 884-892.
7. 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.*(葉菱秀，共同通訊作者) 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.
8. Campagno, C., Wang Q., Pighi C., Cheong T.C., Meng F.L., Poggio T., Yeap L.S. (葉菱秀), 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.
9. Yeap, L.S.* (葉菱秀,，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): 1124-1137. Featured in Preview by Cornelis Murre, Cell, 163(5): 1055-6.
10. Hwang, J.K.*, Alt F.W. and Yeap L.S.* (葉菱秀,，共同第一作者). Related Mechanisms of Antibody Somatic Hypermutation and Class Switch Recombination. Microbiology Spectrum, 2015, 3(1): MDNA3-0037-2014.
11. Yeap, L.S. (葉菱秀，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 and Chromatin, 2009, 2: 12.
12. Chew, J.L, Loh Y.H., Zhang W., Chen X., Tam W.L., Yeap L.S. (葉菱秀), 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.
專利與技術(shù)許可
1. 專利：Pluripotency associated epigenetic factor，2011.03.02,，歐洲,，2288695。
團(tuán)隊(duì)介紹
目前,，本課題組主要由1名助理研究員,、2名技術(shù)員、1名博士后,、2名博士研究生,、2名碩士研究生（其中一名為輪轉(zhuǎn)生）組成。
郝茜,，博士,，助理研究員，郵箱：[email protected]
高波,，博士,，博士后，郵箱：[email protected]
王彬彬,，博士,，技術(shù)員，郵箱：[email protected]
歐陽生群,，碩士,，技術(shù)員，郵箱：[email protected]
占傳棕,，2018級博士,，郵箱：[email protected]
廉朝陽，2019級博士,，郵箱：[email protected]
羅思敏,，2019級碩士，郵箱：[email protected]
殷姿,，2020級碩士,，郵箱：[email protected]
