My research centers on the genetic and molecular mechanisms behind systemic lupus erythematosus (SLE, or lupus), a complex autoimmune disease that impacts multiple organs, including the kidneys, skin, and cardiovascular system. While the causes of lupus are not fully understood, uncovering its genetic basis is crucial for understanding the disease biology.

Unlike Mendelian disorders, lupus results from the combination of multiple genetic variants, gene-gene interactions, and environmental factors. My laboratory uses genetic epidemiology tools, including linkage analysis, genome-wide association studies (GWAS), admixture mapping, and meta-analysis, to identify susceptibility genes in large, well-characterized family collections and case-control cohorts from diverse backgrounds. Our genome scans have helped pinpoint several chromosomal regions harboring lupus susceptibility genes, including ITGAM, CDKN1B,NCF2, and KLF2. Our recent analysis, combining our findings with those of others, has contributed to the mapping of over 180 genetic loci associated with lupus susceptibility.

In the post-GWAS era, the main challenge is turning these statistical associations into mechanistic insights. The Nath lab uses genomic, epigenomic, and functional techniques to understand how lupus-linked variants influence target genes and regulatory networks. By using patient-derived immune cells, primary tissues, cell lines, and induced pluripotent stem cells (iPSCs), we model disease-relevant processes both in vitro and in vivo. Our multidisciplinary toolkit includes:

• High-throughput “omics” technologies such as transcriptomics, epigenomics, and chromatin accessibility.
• 3D chromatin organization assays (such as 3C, Hi-C, ChIP-Seq) for mapping long-range regulatory interactions.
• CRISPR/Cas9 genome editing to introduce or correct risk variants and evaluate their functional effects.

Our primary goal is to link genetic variation to disease phenotypes, thereby identifying new therapeutic targets and reliable biomarkers. These advancements will aid precision-medicinestrategies, enhancing diagnosis, predicting flares, and improving outcomes for patients with lupus and related autoimmune disorders.