Grant: Travel Awards - Institute Community Support

Antibodies secreted by B cells defend the body from invading pathogens and toxic substances. To generate a diverse immune repertoire from a limited set of antibody genes, B cells rely on tightly regulated yet inherently mutagenic mechanisms. While essential for immune diversity, these processes also make B cells uniquely prone to malignant transformation, leading to cancers such as B cell lymphoma. In antigen-activated B cells, an enzyme named activation induced cytidine deaminase (AID) is able to catalyze the deamination of cytosine to form promutagenic uracil, which is a type of genetic lesion that can be processed in an error-prone manner that results in changes, or mutations, in the antibody genes of the B cells. This leads to the diversification of antibody repertoire with improved abilities to eliminate the antigens. FAM72A has been lately suggested to promotes mutagenesis during antibody gene diversification by suppressing error-free repair of AID-induced uracil lesions. However, virtually nothing is known about when, where, and how FAM72A acts in the B cell genome. Using cutting-edge technologies, including CRISPR/Cas9 genome editing, next-generation sequencing, proteomics, model cell lines, and genetic mouse models, our research will uncover novel insights into the mechanisms that drive B cell mutagenesis and genome instability within the immune system. Investigating the regulation and function of the novel FAM72A in B cell lymphoma will also lay the groundwork for developing targeted therapy in FAM72A-overexpressing cancers.