Clavia Ruth Wooton-Kee Lab

The overall goal of my research program is to understand the role of nuclear receptors in hepatic metabolism and chronic liver disease. Our previous and current studies have utilized a mouse model for Wilson’s disease (Atp7b^-/- mouse). Wilson’s disease results from mutations in the Atp7b transporter, which leads to excessive hepatic copper levels and progressive liver disease. Wilson’s disease patients and Atp7b^-/- mice have profound mitochondria and nuclear ultrastructural changes that are likely due to copper induction of redox stress in the hepatocyte and develop spontaneous hepatic nodules between 10-16 months of age. Our lab identified that excessive copper concentrations decreased metabolic nuclear receptor activity (FXR - farnesoid X receptor, HNF4a – hepatocyte nuclear factor, and LRH-1 – liver receptor homolog-1) in vivo, Atp7b^-/- mice, and Wilson’s disease patients.

Our current projects aim to understand the mechanisms driving metabolic and hepatocellular changes in Atp7b^-/- mice and whether ligand activation of nuclear receptors lessens the hepatocellular dysfunction in Wilson’s disease. Future studies will address whether transcriptomic and proteomic signatures in Wilson’s disease overlap other chronic liver diseases.