Determining Regulatory Mechanisms of Human Disease

Thousands of studies of the genetic contributions to human traits and diseases have together revealed that genetic variation in gene regulatory elements causes a substantial fraction of human disease. Mapping the specific mechanisms underlying those genetic associations with disease has potential to improve human health by improving diagnostics and prevention and by nominating new therapeutic targets for subsequent development. Realizing that potential has been made challenging by technical challenges quantifying the specific effect of non-coding variants on gene regulatory element activity, and the downstream consequences of those effects on the expression of one or more target genes. In my talk, I will discuss emerging technologies including high-throughput reporter assays and CRISPR/Cas9-based epigenome editing to map the regulatory contributions underlying GWAS signals. I will specifically focus on applications to investigate the genetic architecture underlying genetic associations with gestational and fetal metabolic health, as well as opportunities to address diverse other areas of health and disease.