Grant: Operating Grant

A unique way that the immune system boosts its response to pathogens is through introducing changes in the genes of some of its responding cell types. B cells are the white blood cells that produce antibodies to neutralize pathogens and toxins. The genetic changes in B cells are carried out by Activation induced cytidine deaminase (AID), an enzyme that alters the sequence and organization of antibody genes, leading to the ability to produce more effective antibodies during an immune response. However, these processes are not perfect and are often misdirected to the wrong genes, or mis-expressed in the wrong cell types. This byproduct of their activity is a leading cause of cancers including lymphoma/leukemia. Thus, these processes are a double-edged sword. The focus of my research is to understand the mechanisms of processes which introduce these genetic changes, the principles that regulate their activity in immune cells vs. other cell types, and the detailed pathways by which their activities regulate biological outcomes including immune response, tissue differentiation and cancer. These studies are essential in order to understand how a system whose job is to help immunity can actually result in cancer. Our results and future studies outlined in this proposal have direct implications on strategies for treatment of cancers.