My lab focuses on understanding and exploiting the complex signaling properties of human membrane proteins with a particular focus on G-protein coupled receptors (GPCRs). GPCRs adopt a very broad set of distinct conformations, the populations and dynamics of which are highly important for determining their diverse signaling outcomes. It is because of their complex signaling profiles as well as their involvement in nearly all areas of human physiology that GPCRs are the targets for >1/3 of all FDA approved drugs. We use cryo-electron microscopy in conjunction with various protein dynamics techniques (principally solution nuclear magnetic resonance (NMR)) to understand at the atomic level how receptor thermodynamics drives activity. To facilitate these studies, we are developing cryoEM and NMR methods suited for detailed characterizations of fleeting yet highly important GPCR intermediate states. In order to exploit our novel mechanistic insights into GPCR signaling, the lab develops new DNA-encoded library (DEL) screening approaches for use in small molecule discovery programs in conjunction with leading academic and industry collaborators. In short, we do GPCR biophysics with an eye towards the clinic!