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.
Lab Website: Erika Darrah Lab
Darrah E, Andrade F. “Editorial: citrullination, and carbamylation, and malondialdehyde-acetaldehyde! Oh my! Entering the forest of autoantigen modifications in rheumatoid arthritis.” Arthritis Rheumatol. 2015 Mar;67(3):604-8. doi: 10.1002/art.38970.
Giles JT, Darrah E, Danoff S, Johnson C, Andrade F, Rosen A, Bathon JM. “Association of cross-reactive antibodies targeting peptidyl-arginine deiminase 3 and 4 with rheumatoid arthritis-associated interstitial lung disease.” PLoS One. 2014 Jun 5;9(6):e98794. doi: 10.1371/journal.pone.0098794. eCollection 2014.
Joseph CG, Darrah E, Shah AA, Skora AD, Casciola-Rosen LA, Wigley FM, Boin F, Fava A, Thoburn C, Kinde I, Jiao Y, Papadopoulos N, Kinzler KW, Vogelstein B, Rosen A. “Association of the autoimmune disease scleroderma with an immunologic response to cancer.” Science. 2014 Jan 10;343(6167):152-7. doi: 10.1126/science.1246886. Epub 2013 Dec 5.
Romero V, Fert-Bober J, Nigrovic PA, Darrah E, Haque UJ, Lee DM, van Eyk J, Rosen A, Andrade F. “Immune-mediated pore-forming pathways induce cellular hypercitrullination and generate citrullinated autoantigens in rheumatoid arthritis.” Sci Transl Med. 2013 Oct 30;5(209):209ra150. doi: 10.1126/scitranslmed.3006869.
Ferucci ED, Darrah E, Smolik I, Choromanski TL, Robinson DB, Newkirk MM, Fritzler MJ, Rosen A, El-Gabalawy HS. “Prevalence of anti-peptidylarginine deiminase type 4 antibodies in rheumatoid arthritis and unaffected first-degree relatives in indigenous North American populations.” J Rheumatol. 2013 Sep;40(9):1523-8. doi: 10.3899/jrheum.130293. Epub 2013 Aug 1.
Darrah E, Giles JT, Ols ML, Bull HG, Andrade F, Rosen A. “Erosive rheumatoid arthritis is associated with antibodies that activate PAD4 by increasing calcium sensitivity.” Sci Transl Med. 2013 May 22;5(186):186ra65. doi: 10.1126/scitranslmed.3005370.
Darrah E, Andrade F. “NETs: the missing link between cell death and systemic autoimmune diseases?” Front Immunol. 2013 Jan 17;3:428. doi: 10.3389/fimmu.2012.00428. eCollection 2012.
Darrah E, Rosen A, Giles JT, Andrade F. “Peptidylarginine deiminase 2, 3 and 4 have distinct specificities against cellular substrates: novel insights into autoantigen selection in rheumatoid arthritis.” Ann Rheum Dis. 2012 Jan;71(1):92-8. doi: 10.1136/ard.2011.151712. Epub 2011 Aug 21.
Kolfenbach JR, Deane KD, Derber LA, O'Donnell CI, Gilliland WR, Edison JD, Rosen A, Darrah E, Norris JM, Holers VM. “Autoimmunity to peptidyl arginine deiminase type 4 precedes clinical onset of rheumatoid arthritis.” Arthritis Rheum. 2010 Sep;62(9):2633-9. doi: 10.1002/art.27570.
Andrade F, Darrah E, Gucek M, Cole RN, Rosen A, Zhu X. “Autocitrullination of human peptidyl arginine deiminase type 4 regulates protein citrullination during cell activation.” Arthritis Rheum. 2010 Jun;62(6):1630-40. doi: 10.1002/art.27439.