The major focus of Dr. Baechler Gillespie’s laboratory is the use of genomic and proteomic techniques for identification and validation of biomarkers for human autoimmune disease. Currently there are three major projects based on a large biorepository of blood and urine samples from patients with systemic lupus erythematosus (SLE). The first project seeks to identify gene expression biomarkers of SLE disease activity using blood cell RNA from longitudinally-collected samples. In a second study, a parallel approach is being used to identify serum protein biomarkers of SLE activity. In both of these studies, we hope to identify biomarkers that reflect current disease activity, as well as those that precede disease flare. The results of these studies will increase our understanding of the pathogenic mechanisms underlying disease flare and may be useful in the clinical monitoring of patients with SLE.

A third project focuses on the genetic determinants of blood cell gene expression in SLE. A number of interesting gene expression signatures have already been identified in SLE patients, including a signature that reflects activation of the type I interferon pathway. However, it is has not been shown whether these signatures are causative for disease or are instead effects of the disease process. We are generating both whole genome gene expression data (microarray) and genotype data (500K SNP chips) on 300 SLE patients. The goal is to identify genetic determinants of SLE gene expression signatures. This study may reveal biological pathways that lead to SLE, and would thus identify new targets for therapy. The results will also help us prioritize candidate genes in the era of genome-wide association studies.