Leng Siew Yeap-上海市免疫学研究所

Name:Leng Siew Yeap
Office Location:Room 903, No. 5 Bldg., West Area, 280 South Chongqing Rd., Shanghai
Telephone:86-021-63846590-776726
Email:yeaplengsiew@shsmu.edu.cn

Education

2003

U. Msia Sabah

B.Sc.

2010

Cambridge University

Ph.D.

Career

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.