Signal transduction across cell membranes plays a central role in human physiology and disease, yet the mechanistic details underlying transmembrane signaling remain poorly understood. Our research aims to elucidate the molecular basis of membrane protein signaling using techniques including protein engineering, structural biology, and pharmacology. In particular, we are focused on the study of proteins important in human health and disease, including G protein-coupled receptors and other proteins that regulate neurotransmission and metabolic homeostasis.

G protein-coupled receptors (GPCRs) are cell-surface receptors that regulate neurotransmission, cardiovascular function, metabolic homeostasis, and many other physiological processes. Due to their central role in human physiology, these receptors are among the most important targets of therapeutic drugs, and are they among the most extensively studied proteins. To better understand GPCR signal transduction at a molecular level, we are using structural biology and biophysical methods to study model GPCRs such as muscarinic acetylcholine receptors. In addition, we are using new approaches in combinatorial biology to facilitate structural studies and to create protein ligands of GPCRs.

We are also interested in signal transduction pathways that remain less extensively studied than GPCRs, particularly receptors involved in the regulation of human metabolic homeostasis. In the long term, we hope to leverage our understanding of molecular signal transduction to guide the development of new and better therapeutics that modulate these pathways.