Nutrient transport and metabolism in health and disease
The Claxton laboratory employs tools of biochemistry and biophysics to explore the structure/function paradigm of membrane-integrated phosphatases and transporters to understand their contribution to normal metabolic processes and disease. Our primary target is liver glucose-6-phosphatase that couples the uptake of glucose-6-phosphate from the cytosol into the ER lumen by a dedicated transporter (G6PT) with its hydrolysis by the catalytic subunit (G6PC1). Disregulation or malfunction of this catalytic system contributes to metabolic disorders such diabetes and glycogen storage disease. Our overall approach integrates knowledge of protein structure with sophisticated spectroscopic methods and reaction kinetics to develop mechanistic models of functional dynamics. The lab capitalizes on state-of-the-art instrumentation at Vanderbilt, including cryogenic electron microscopy (cryo-EM) and electron paramagnetic resonance (EPR), to facilitate discoveries. Our goal is to uncover relationships between target molecular properties and disease-linked variants to aid rational design of therapeutic strategies.