Grant: Regional Partnership Program New Investigator Award

A unique way that the body enhances immunity to pathogens is through introducing subtle changes at the genetic level. There are two main categories of genetic changes. The first type occurs in the genome of our B cells. B cells are the white blood cells of the immune system which produce antibodies necessary to fight pathogens. 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 stronger antibodies. The second type of genetic changes are those that take place in the genes of viruses. A set of AID-related enzymes known as APOBECs introduce changes in the genes of viruses as a means of deactivating the virus. They specifically act on retroviruses, most notably HIV. Overall, genetic alterations are an effective means to boost immunity; however, these processes are not perfect and can be misdirected to the wrong genes. Such unwanted genetic changes have been shown to result in 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 the processes which introduce genetic changes in the immune system, the facets through which they modulate immunity, and how they are 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 will have implications on strategies for treatment of leukemia/lymphomas and HIV.