Structure and Function of Arrestins and their Role in Cell Signaling
Department of Pharmacology
417D Preston Research Building
The lab studies the regulation of signaling by G protein-coupled receptors (GPCRs), focusing on structure, function, and biology of arrestin proteins. The lab has two groups of projects. Our work in vision focuses on visual arrestin interactions with light receptor rhodopsin. These projects involve a variety of methods, from structural, biochemical, and biophysical work with purified proteins to electroretinography in living mice. We engineered enhanced mutants that do not require rhodopsin phosphorylation for tight binding. We are testing the ability of these mutants to compensate for defects of rhodopsin phosphorylation in genetically modified mice. The initial success of our proof-of-concept studies suggest that this is a viable approach for compensational gene therapy in vision, as well as in other systems where excessive GPCR signaling underlies the pathology. We are also studying the interactions of non-visual arrestins with numerous GPCRs abundant in the nervous system, such as dopamine receptors (involved in addiction, Parkinson’s disease), NPY receptors (feeding behavior and obesity), etc. As arrestins play a role in many branches of signaling underlying life-or-death decisions in the cell, we are working on designing arrestin-based molecular tools that can prevent neurodegeneration.
For more information, please visit the lab website.