October 17, 2014
Understanding Autoimmune Disease at the Molecular Level
Autoimmune conditions imply a dysregulation of the immune system at the genetic level, often involving post-translational modifications. In an effort to understand their specific role in autoimmunity, we examine one family of enzymes that is capable of making such modifications, the Protein Arginine Deiminase (PADI) family. In particular, we chose to extensively analyze the functions of PADI4 at the molecular level. Research has shown that citrullination modifications can produce autoimmune disease symptoms in Rheumatoid Arthritis, Systemic Lupus Erythematosus and Multiple Sclerosis patients. These symptoms result, at least in part, from anti-citrullinated protein antibodies produced in the patients. Using META-analysis and an array of biochemical techniques, we investigate the molecular details of this type of enzyme modification by PADI4 to further understand the functional link to autoimmune disease. Ultimately, we hope to develop a potent and highly specific inhibitor to each PADI enzyme to address the negative in vivo effects of protein modification.
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