defining molecular mechanisms of drug action

Structural Pharmacology

We are an interdisciplinary research group that utilizes structural biology, biochemical, biophysical, chemical biology, and cellular/molecular pharmacology methods to explore structure-function mechanisms of nuclear (hormone) receptor transcription factors. 

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. 

We use interdisciplinary structural biology and functional approaches to understand how activation and repression of nuclear receptor transcription is regulated on the molecular and cellular level, including the influence of small molecule ligands—natural/endogenous ligands, synthetic ligands, and FDA-approved drugs used clinically.