Nuclear receptors are ligand-dependent transcription factors that function in part by recruiting chromatin remodeling machinery to promoter regions of target genes. Nuclear receptors exert powerful influences on all aspects of human physiology, and dysfunctional nuclear receptor signaling is linked to many human diseases including cardiovascular, metabolic, and neurological disorders, cancer, and inflammation. The ligand-regulated nature of nuclear receptor function has provided opportunities to develop synthetic ligands to pharmacologically probe the function of nuclear receptors in normal and diseased states, which has provided therapeutic treatments for a variety of disorders including >10% of FDA approved drugs.
The goal of our research is to understand how activation and repression of nuclear receptor transcription is regulated on the structural and molecular level, including the influence of small molecule ligands—natural/endogenous ligands, synthetic ligands, and FDA-approved drugs used clinically. We use biomolecular NMR spectroscopy as a main structural technique, but also apply a variety of structural, computational, biophysical, and functional approaches including X-ray crystallography, molecular dynamics simulations, biophysical and biochemical assays, and cellular assays to connect our molecular and structural findings on nuclear receptors to cellular functions.