"Systematic lupus erythematosus (SLE or lupus) is a debilitating autoimmune disease, characterized by abnormal immune cell response. While the etiology of SLE is incompletely understood, a substantial genetic contribution is well established. Therefore, genetic studies have the potential to delineate the pathogenic mechanisms of SLE. Several genome-wide association studies (GWAS) have identified over 100 SLE predisposing loci, mostly defined by single nucleotide polymorphisms (SNPs). Recent studies highlighted GWAS loci are enriched within regulatory elements (i.e., enhancers), likely to modulate target gene expression. Even though they are thought to play a role in gene regulation, it is unclear which genes they regulate and in which cell types or physiological contexts.
To systematically delineate the regulatory SNPs (rSNPs) and their impact on target genes, we propose to apply HiChIP experiments in human primary immune cells, relevant to SLE (T-cells and B-cells). This will gives us a 3D view of our sequence data which can directly associate rSNPs in distal regulatory sequences with the transcriptional targets that they regulate. Discovery of rSNPs and their target genes will significantly advance our knowledge of SLE genetics, and yield directions for future in-depth mechanistic research for understanding lupus susceptibility." - Dr. Swapan Nath