Dr. Darrah is primarily interested in the mechanisms underlying the development and progression of autoimmunity in RA, with a particular focus on the peptidyl arginine deiminase (PAD) enzymes. These enzymes carry out the post-translational conversion of arginine to citrulline in a calcium-dependent reaction to generate the hallmark targets of the autoimmune response in RA, citrullinated proteins. PAD4 is a member of this enzyme family and is itself a target of autoantibodies in RA. Dr. Darrah is focused on understanding the development of these PAD4-activating autoantibodies over time and how they contribute to the development of erosive disease. Studies are underway to determine if the newly discovered antibody is mimicking a naturally-occurring PAD4 binding partner and to identify potentially pro-inflammatory effects of citrullinated proteins on effector cells of the immune system.