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Orange’s research focuses on characterizing the molecular mechanisms that underlie phenotypes of rheumatic diseases such as rheumatoid arthritis, osteoarthritis, and systemic sclerosis. Her group developed fingerstick RNA sequencing to empower patients to participate in longitudinal genomic studies from home and used this approach to discover B cells, followed by PRIME cells, which are fibroblast like cells in the circulation, that are increased in blood just prior to rheumatoid arthritis flares. Using this approach, they also discovered patients with periodontal disease who experience repeated episodes of subclinical oral bacteremia, which in turn trigger an inflammatory monocyte response. This same inflammatory monocyte is seen in the joints of patients with rheumatoid arthritis who do not improve with usual immunosuppressive therapy. The discovery that oral bacteremia is a trigger for these inflammatory monocytes shed light on the clinical observation that rheumatoid arthritis patients with concurrent periodontal disease tend to receive less benefit from immunosuppression. The Orange group continues to use longitudinal gene expression profiling to decipher the order of immune events that correspond to changes in inflammatory diseases over time in an array of clinical scenarios such as treatment discontinuation, progression of disease, and circadian fluctuations in disease activity.

Through collaborations with multidisciplinary teams and consortiums such as the NIH-industry sponsored Accelerating Medicines Partnership (AMP) and Restoring Joint Health and Function to Reduce Pain Consortium (RE-JOIN), Orange studies the molecular phenotypes of cells in synovial tissue in rheumatoid arthritis and osteoarthritis. Her group has applied computer vision approaches to refine quantification of synovial inflammation and applied a variety of machine learning approaches to integrate bulk and single cell RNA sequence data with histology and patient reported data to provide insight into disease subsets, predict treatment responses, as well as clinical worsening.

Orange is also an attending physician in rheumatology and a member of the Inflammatory Arthritis Center at the Hospital for Special Surgery.