Research Interests

My laboratory primarily focuses on understanding the mechanism by which hormone binding to G protein-coupled receptors (GPCRs) lead to activation of signaling cascades. GPCRs are cell surface proteins that detect environmental stimuli and are key conduits for intracellular communication. This superfamily of genes (3rd largest in the human genome) contains members responsible for vision, smell and taste. Family members also serve as the primary receptors for hormones such as epinephrine, serotonin and dopamine, as well as chemokines, to name few. Following activation by this vast array of stimuli GPCRs couple to the heterotrimeric family of G proteins, intracellular proteins that serve as arbiters between the receptor and downstream effector such as adenylyl cyclase, phospholipase C and ion channels, to name a few. GPCRs continue to be the most popular targets for all therapeutics currently on the market, yet off-target activity, as well as our poor understanding for the structural basis of ligand efficacy, remain as major contributors to adverse reactions or side-effects.  My laboratory is keenly interested in the nature of the allosteric relationship between hormone binding and G protein activation. We utilize  biochemical, biophysical and pharmacological approaches to study how hormones and ligands influence receptor-G protein coupling and to understand the mechanisms underlying the implicit cooperativity. Achieving a better understanding of the structural and functional basis of this allostery will help us understand the mechanisms underlying ligand efficacy.  Together with structure-guided drug discovery initiatives we hope to use these models to develop safer and more efficacious therapeutics.