Grant: Operating Grant

A unique way that the body enhances immunity to pathogens is through introducing subtle changes at the genetic level in some cells of the immune system. B cells are the white blood cells which produce antibodies necessary to neutralize pathogens and toxins. The genetic changes in B cells are carried out by Activation induced cytidine deaminase (AID), an enzyme that makes changes to the antibody genes, leading to the production of stronger and better antibodies. Overall, genetic alterations are an effective means to boost immunity, with the caveat that these processes are not perfect and can be misdirected to the wrong genes. Such unwanted genetic changes have been shown to be a leading cause of cancers of immune cells, namely lymphoma/leukemia. Thus, these processes are a double-edged sword. The focus of my research is to understand the mechanisms of processes which introduce genetic changes in the immune system, the facets through which they modulate immunity, and how they are regulated and targeted to certain genes. These studies are essential in order to understand how a system that is there to help immunity can actually result in the generation of cancer. Our results and future studies outlined in this proposal have direct implications on strategies for treatment of leukemia/lymphomas.