Lab Leader: Leng Siew Yeap

Lab Name: Laboratory of Antibody Diversification

Lab Info：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. We are interested in dissecting the genetic pathways that generate these rare mutational outcomes during Immunoglobulin (Ig) Somatic Hypermutation processes. Our 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. Our ultimate aim is to generate humanized antibody mouse models based on our 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, we are also interested in collaborating with clinicians to identify the antibodies and antigens that resulted in these diseases.

Lab Members: