Grant: Project Grant

Excessive inflammation is the root cause of many debilitating human diseases, including heart disease, autoimmune diseases and cancer. Therefore, it's essential to identify and understand the mechanisms that keep inflammation in check. We recently reported a novel role of TRAF1, a signaling adapter protein, in controlling inflammation. We showed that people with a genetic variation in their TRAF1 make less TRAF1 protein, which loosens the "brakes" on their inflammatory cells and increases their risk of developing rheumatoid arthritis. However, therapies targeting TRAF1 in inflammatory and autoimmune diseases is complicated because TRAF1 plays additional, often opposing, roles in other immune pathways. Therefore, this proposal aims at dissecting the disparate TRAF1 functions, by identifying the sites of TRAF1 interaction with these pathways, and mutating them to affect one pathway at a time. This allows us to design therapies targeting specific TRAF1 functions that provides favorable therapeutic outcome for the aforementioned diseases.