Understanding the Cellular Pathways of Nuclear Receptor Activation

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The success of drug treatment depends critically on specificity, i.e., stimulation of a therapeutic response at a target site, and avoidance of activity at other (potentially toxic) locations. This project aims to 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 intends to employ molecular, structural and cell biology approaches to map drug-binding protein-receptor interactions and to determine how the structure of these complexes dictates receptor activation. The data could provide a roadmap to design drugs that interact with the right protein in the right tissue and in doing so dramatically enhance drug specificity.