Laura Wingler, Ph.D.

Research

The Wingler lab will unravel how different signaling molecules can activate the same receptor yet induce distinct cellular responses. Even though G protein-coupled receptors (GPCRs) are the largest single class of drug targets, only a small fraction of these receptors are targeted clinically, often due to their pleiotropic roles in vivo. Much of this complexity stems from the fact that many GPCRs have more than one endogenous ligand. While it is known that different GPCR ligands can cause the receptors to activate different cellular pathways, both the biochemical mechanisms underlying this phenomenon and the physiological implications of this promiscuity remain unclear. As a postdoctoral fellow, I collaboratively developed methods to isolate probes that can distinguish between receptors that are even slightly different in shape. My group is now applying these strategies to identify probes that can recognize or modulate the same receptor bound to different ligands. These probes will give us the tools to disentangle complex ligand-receptor networks, and they could inspire more nuanced strategies to therapeutically target receptors previously believed to be “undruggable.”