Overall, it is the goal of Dr. Mamula's laboratory to understand the mechanisms that may shift this balance toward the initiation of anti-self immune responses. Seminal work from the Mamula lab elucidated the biochemical forms of autoantigens capable of breaking immunologic tolerance to intracellular autoantigens in systemic lupus erythematosus (SLE), and type 1 diabetes (T1D). Simply put, Dr. Mamula examines posttranslational protein modifications that alter cellular biology and immunity. These studies have now been applied to the development of novel therapeutic approaches in developing anti-tumor vaccines in breast cancer and colon cancer. In addition, studies from the Mamula laboratory first demonstrated the ability of B cells to present autoantigens in the triggering of T cell autoimmunity and in the phenomenon of epitope spreading in lupus autoimmunity. This work preceded more recent studies illustrating the how B cells transfer autoantigens to other antigen presenting cells, including dendritic cells and macrophages.