Nuclear Receptor Function in Hepatic Pathology

与本项目特别相关的两个具体领域是筛选代谢信号的影响 和代谢疾病对肝脏microRNA表达的影响，以及NRs及其靶点在不良反应中的作用。 药物反应。该项目基于两个一般假设：1）微RNA表达改变， 反应核受体活化和其他代谢信号在肝脏中，允许非增殖性 肝细胞随着时间的推移改变其功能。2)药物不良反应中肝毒性的诱导是 与NR表达、其共调节因子和下游代谢产物的大规模改变相关。 靶点和不同类别的肝毒性剂引起不同的反应。我们将通过以下方式来检验这两种假设： 利用该链在最初开发的高通量QPCR筛选技术， 项目的第一阶段。

Two specific areas with particular relevance to this project arescreening for the impact of metabolic signals and metabolic disease on hepatic expression of microRNAs, and the role of NRs and their targets in adverse drug reactions. This project is based on two general hypotheses: 1) Micro RNA expression is altered in response to nuclear receptor activation and other metabolic signals in the liver, allowing non-proliferative hepatocytes to alter their function over time. 2) The induction of hepatotoxicity in adverse drug reactions is associated with large scale alterations in expression of NRs, their coregulators and downstream metabolic targets, and distinct classes of hepatotoxic agents elicit distinct responses. We will test both hypotheses by leveraging the ongoing high throughput QPCR screening technologies developed by this Strand in the initial Phase of the NURSA project.