We currently pursue structural and biochemical studies of human nuclear receptors, which are lipid regulated transcription factors that play central roles in development, cancer, stress and metabolism. The ability of nuclear receptors to control gene programs in response to small lipophilic molecules makes them ideal pharmaceutical targets for a wide range of metabolic and neoplastic diseases. Broadly, our goals are to understand the structural mechanisms driving transcriptional activation within nuclear receptors with a focus on proteins involved in phospholipid-mediated signaling and transport. This includes characterzing interactions between nuclear receptors and their ligands, other proteins, DNA, and RNA. We use sophisticated structural biology techniques such as x-ray crystallography and mass spectrometry coupled with an array of biochemical techniques to gain a molecular-level understanding of transcriptional signaling. Studies are complemented by analysis of these processes in cultured human and rodent cells and we have a strong track record of collaboration, which has led to numerous contributions in the nuclear receptor field and to the lipid signaling community.
A second project in the lab centers on understaning the evolutionary forces that dicate protein function. In collaboration with Dr. Joseph Thornton at the University of Chicago (Chicago, IL), and Dr. Eric Gaucher at the Georgia Instititute of Technology (Atlanta, GA), we have made seminal contributions to the field of molecular evolution using transcrption factors and enzymes to understand the evolutoin of new function.