Erika Darrah, Ph.D. is an Associate Professor in Medicine. She received her Ph.D. in Immunology at the Johns Hopkins University School of Medicine. During her doctoral training, she characterized antigen-specific T cell responses in rheumatoid arthritis and implicated granzyme B in the revelation of cryptic autoimmune epitopes. After completing a post-doctoral fellowship in the Division of Rheumatology studying autoantibodies in RA under the mentorship of Dr. Antony Rosen, she joined the faculty in the Division of Rheumatology to continue her investigative pursuit of autoimmunity in rheumatoid arthritis.
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. In work continued from her post-doctoral training, Dr. Darrah discovered a subset of PAD4-binding antibodies with the unique capacity to turn the enzyme on in the presence of physiologic levels of calcium. Patients with these antibodies have a greater burden of erosive joint disease and are most likely to progress in their disease course despite being treated with standard therapies. These novel antibodies may therefore identify patients who would benefit most from early aggressive therapy.
Currently, 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.