Research Interests
Antibody plays a crucial role in the immune system to fight against invading pathogens. Elegant genetic mechanisms are involved to diversify the antibody repertoire so that we have the capacity to generate antibodies against an almost infinite variety of different antigens that human bodies may encounter during our lifetime. The primary antibody repertoire is established within the bone marrow during B cell development through V(D)J recombination. Upon cognate antigen encounter, B cells express Activation Induced cytidine Deaminase (AID) to further diversify antibody repertoire to produce high affinity antigen binding antibodies with altered isotypes through somatic hypermutation (SHM) and class switch recombination (CSR). AID deaminates cytosines to uracils at the Immunoglobulin (Ig) locus, and uracils need to be recognized and processed in an error-prone manner by the cellular DNA repair machinery from base excision repair (BER) and mismatch repair (MMR) pathways to produce mutagenic outcomes required to generate Ig diversity, a process named mutagenic DNA repair. My research group uses biochemical, molecular, genetic cell line and mouse models, and immunological tools to study the mutagenic DNA repair mechanisms that allow antibody production by B cells. We are particularly interested to understand the interaction of BER and MMR pathways and their differential processing AID-induced uracil lesions during antibody SHM and CSR. We also investigate DNA repair and its influence on off-target AID deamination, as this has been linked to lymphomagenesis.
Sub-disciplines
Gene diversification, B cell, DNA repair, mutagenesis