My research focuses on understanding the etiology and pathogenesis of systemic autoimmune diseases. This requires unraveling vast networks of interconnected immune responses, a task that exceeds the limitations of traditional laboratory methods. My group applies high-throughput/high-content precision medicine approaches to this problem. Our primary focus is defining, at a systems level, the pathways that influence the regulation and development of autoimmune responses.

I was involved in some of the early candidate gene association studies and then in the whole genome association studies in lupus. I have also been intimately involved with large consortium studies and many follow-up fine mapping studies through my management of several large collections of lupus samples and data in the OMRF Biorepository and Sample Procurement Core. These results led to studies on the functional effects of disease-associated genetic variants, particularly in genes affecting the complement regulatory proteins/receptors, innate immune responses, and B cell signaling pathways.

To gain a high-level view of immune function in patients with autoimmune disease, we use a systems biology approach to combine data from our genetic/genomic studies, innovative biomarker assessments, cellular immunophenotyping experiments, and single-cell proteomics analyses. Because multiple immune pathways can lead to the same autoimmune disease diagnosis, we also use these multidimensional datasets and associated clinical data to cluster patient subpopulations and model altered pathways in various populations. We apply these methods both in translational studies of cross-sectional and longitudinal autoimmune disease cohorts, and in investigator-initiated clinical trials. The ultimate goal of this work is to enable more accurate diagnosis, risk assessment before clinical disease onset, and prediction of therapeutic responses in order to improve patient care.