Rheumatoid arthritis is a chronic inflammatory condition affecting almost 1% of the world’s population. The etiology of this complex disease is still unknown. However, considerable research interest has focused on the appearance of disease specific autoantibodies that recognize a subset of our own proteins, containing a modification called citrulline. Some of the most specific forms of rheumatoid arthritis autoantibodies recognize citrullinated proteins, appear very early in the disease, and are predictive of clinical outcome. A strong association has recently been discovered between susceptibility to rheumatoid arthritis and mutations in a gene responsible for protein citrullination.
Dr. Fast will seek to determine whether these mutations introduce any functional changes into the activity or calcium regulation of this important enzyme, PAD4. In addition, these studies will lay the groundwork for future studies of PAD4 and for the design of small molecule inhibitors that could potentially be used for developing therapeutic drugs.