Understanding the Cellular Pathways of Nuclear Receptor Activation

The success of drug treatment depends critically on specificity, ie, stimulation of a therapeutic response at a target site, and avoidance of activity at other (potentially toxic) locations. This project will explore how drug interactions with binding proteins in the cytosol can induce nuclear transport and tissue specific activation of nuclear receptors - a major drug target. The project will employ molecular, structural and cell biology approaches to map drug-binding protein-receptor interactions and will determine how the structure of these complexes dictates receptor activation. The data will provide a roadmap to design drugs that interact with the right protein in the right tissue and in doing so dramatically enhance drug specificity.