Dr. Baranski received his MD and PhD from Washington University School of Medicine in 1992 where he studied molecular biology with Stuart Kornfeld (1987-91). He did his medicine and endocrinology clinical training at UCSF where he also trained in signal transduction and endocrinology research with Henry Bourne (1995-98). Dr. Baranski joined the faculty in the Department of Medicine in 1998.
Our laboratory studies signal transduction by G protein-coupled receptors, a superfamily of heptahelical transmembrane proteins. The receptors act as elegantly engineered switches, receiving signals involved in many physiologic processes — blood pressure regulation, glucose homeostasis, sight and smell — to turn on specific signaling cascades within cells. Remarkably, we devote more than 3 percent of our entire genome to encoding these receptors. Despite their widespread importance, we do not understand how the receptors actually function as ligand-activated switches.
We use engineered yeast to apply the power of genetics to the study of signaling by human G protein-coupled receptors. In one strategy, we use saturation mutagenesis to force segments of a chemoattractant receptor to evolve at an extremely high rate. We have generated the largest set of functional mutations within any G protein-coupled receptor. Combined with bioinformatic approaches, this data allows us to build higher-resolution models of the receptor structure. Insights into how ligands activate receptors will aid in drug design and greatly impact medicine; more than half of currently prescribed pharmaceuticals target G protein-coupled receptors.
A new project in the lab involves developing a model system of glucose toxicity in the simple model organism Drosophila melanogaster to answer a basic question: Why is high glucose toxic to cells? We have performed screens in flies to identify genes that contribute to the effects of a high glucose diet on developing larvae. In addition, we can now perform metabolic phenotyping on the flies to characterize the affects of many genes to the ability of the animal to tolerate high glucose.