Regulation of Bilirubin Metabolism by the Receptor CAR

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DESCRIPTION (provided by applicant): The nuclear hormone receptor CAR (Constitutive Androstane Receptor) is a key regulator of the metabolism of a wide range of xenobiotic compounds. This proposal is focused on a newly identified role of CAR in the bilirubin metabolism pathway. Preliminary results demonstrate that CAR is a key regulator of bilirubin clearance pathway in mice. The overall goals of this project are to extend this finding to human CAR and begin to explore its role in neonatal jaundice as well as its role in mediating a well-known Chinese medicine in the treatment of jaundice. The specific aims of this proposal are: 1) Determine the role of human CAR in regulation of bilirubin metabolism. 2) Compare the level of expression of CAR in human neonatal livers with adult livers. 3) Determine the role of CAR in mediating the effect of a Chinese medicine, Yinzhi Huang, in treatment of human jaundice. The findings will elucidate the essential role of CAR in bilirubin metabolism and have significant implications for development of more potent drugs for the treatment of human jaundice and other related diseases.