Nuclear Receptor Signaling Pathways
 A new branch of nuclear receptors important in metabolic regulation |
Nuclear receptors are a special group of transcriptional factors that are activated by their cognate ligands. A new branch of nuclear receptors was recently identified to play pivotal roles in regulation of different important metabolism pathways. These nuclear receptors work as sensors of different metabolic signals and regulate the expression profiles of essential genes in different metabolism pathways. Studies in this area have
generated significant impact in many human diseases such asdiabetes, obesity, cancer and aging.
Our previous studies have mainly focused on three members of this group of nuclear receptors, which play essential roles in regulating the nutritional and chemical metabolism. For example, Farnesoid X Receptor (FXR) is important for bile acid homeostasis. The Constitutive Androstane Receptor (CAR) and Pregnane X Receptor (PXR) are key regulators of metabolism of both xenobiotics and endobiotics such as drugs, bilirubin and bile acids. Our recent interesting results indicate that sustained CAR activation promotes cancer formation, which may provide a novel link between metabolic regulation and carcinogenesis. By using both genetically engineered mouse models and pharmacological tools, my laboratory will be interested in delineating the molecular pathways of nuclear receptor signaling and their relationship to human diseases.
The current research projects in this laboratory focus on 1) Identification of physiological signal molecules and signaling pathways that activate nuclear receptors; 2) Elucidation of the cell growth pathways regulated by nuclear receptors and its relationship to carcinogenesis; 3) Generation of new mouse models for the studies of metabolic diseases and cancers. Our long-term goal is to identify the novel components in nuclear receptor-mediated signaling pathways and provide the new targets for drug discovery.