Meng Feilong

Biography

MENG Feilong is a Professor of Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, hanghai, China. Research Interests: The Meng lab studies genome alterations in B-lymphocytes and cancer cells using emerging high throughput genomic technologies and mouse genetic models. Upon pathogen stimulation, resting naïve B cells can undergo genome alterations including Immunoglobulin variable region exon somatic hypermutation (SHM) and Immunoglobulin Heavy chain (IgH) class switch recombination (CSR), to generate antibodies with higher affinity and proper effector functions. Activation induced cytidine deaminase (AID) initiates both SHM and CSR processes via cytidine deamination of single-strand (ss) DNA targets in a transcription-dependent manner. While largely specific for Ig genes, AID also acts on a limited set of off-targets, generating oncogenic translocations and mutations that contribute to B cell lymphoma. Our studies have revealed roles of RNA exosome and convergent transcription in AID-initiated programmed DNA lesions and genomic instability. In this context, convergently transcribed intragenic super-enhancers (SEs) are the major source of genome instability in B cell lymphomas. Similar mechanisms could contribute to AID-initiated antibody somatic hypermutations (SHM) and AID/Apobec initiated clustered mutations (kataegis) in various cancer genomes. We will use B cell immune system to further investigate the roles of AID/Apobec DNA mutator enzymes and non-coding RNA processing in genome instability. Current projects include 1). Regulatory RNA; 2). Germinal center B cells and Somatic Hypermutation; 3). AID/Apobec activity regulation in B cells and other tumor cells.

Research Interest

The Meng lab studies genome alterations in B-lymphocytes and cancer cells using emerging high throughput genomic technologies and mouse genetic models. Upon pathogen stimulation, resting naïve B cells can undergo genome alterations including Immunoglobulin variable region exon somatic hypermutation (SHM) and Immunoglobulin Heavy chain (IgH) class switch recombination (CSR), to generate antibodies with higher affinity and proper effector functions. Activation induced cytidine deaminase (AID) initiates both SHM and CSR processes via cytidine deamination of single-strand (ss) DNA targets in a transcription-dependent manner. While largely specific for Ig genes, AID also acts on a limited set of off-targets, generating oncogenic translocations and mutations that contribute to B cell lymphoma. Our studies have revealed roles of RNA exosome and convergent transcription in AID-initiated programmed DNA lesions and genomic instability. In this context, convergently transcribed intragenic super-enhancers (SEs) are the major source of genome instability in B cell lymphomas. Similar mechanisms could contribute to AID-initiated antibody somatic hypermutations (SHM) and AID/Apobec initiated clustered mutations (kataegis) in various cancer genomes. We will use B cell immune system to further investigate the roles of AID/Apobec DNA mutator enzymes and non-coding RNA processing in genome instability. Current projects include 1). Regulatory RNA; 2). Germinal center B cells and Somatic Hypermutation; 3). AID/Apobec activity regulation in B cells and other tumor cells.