Nuclear Receptor Functional Profiling in Metabolism and Disease

核受体家族由配体激活的转录调节因子组成， 被认为是人体发育和代谢稳态的关键调节因子。许多共同 诸如动脉粥样硬化、肝和肺纤维化、癌症和慢性炎症的疾病， 他们的起源是失去代谢或发育控制。我们将重点探讨mRNA表达 人类疾病中的核激素受体谱，包括但不限于非酒精性 脂肪性肝炎（NASH）、动脉粥样硬化和糖尿病、皮肤病（例如牛皮癣）、脑肿瘤和骨髓瘤 白血病此外，将使用选择性小鼠模型来检查mRNA NR的表达模式。 在代谢和炎症疾病进展的早期和晚期阶段， 动脉粥样硬化分析将通过定量PCR NR PCR SA平台实现，该平台提供 一种灵敏、高定量的NR mRNA水平分析方法。从这些收集的数据 研究将包含在共享的生物信息学资源中，供更广泛的科学研究人员进行数据挖掘。 社区此外，该项目的主要目标之一是开发新的分析工具， 确定和改变核受体家族所有成员在特定细胞中的表达， 组织中此外，我们还将设计、开发和验证一种全面的慢病毒shRNA敲除方法， 这是一个针对整个NR家族的库。最后，我们将使用该文库来询问细胞系和动物 代谢，炎症和癌症状态的模型，其中受体已被证明具有动态 和/或显性表达谱。NR慢病毒shRNA敲低文库将在其他 CNOSA成员的最终目标是为研究界提供一个强大的新工具， 分析NR函数。

The nuclear receptor family is made up of ligand-activated transcriptional regulators that have been implicated as key regulators of development and metabolic homostatsis of the human body. Many common diseases such as atherosclerosis, hepatic and pulmonary fibrosis, cancer and chronic inflammation have their origins in loss metabolic or developmental control. We will focus on exploring the mRNA expression profile of nuclear hormone receptors in human diseases including but not limited to nonalcoholic steatohepatitis (NASH), atherosclerosis and diabetes, skin diseases (eg psoriasis), brain tumors and myeloid leukemia. In addition, selective mouse models will be used to examine the expression pattern of mRNA NR family during early and late phases of progression of metabolic and inflammation diseases such as atherosclerosis. Profiling will be achieved through the quantitative PCR NR NURSA platform which provides a sensitive and highly quantitative method for analyzing NR mRNA levels. The data collected from these studies will be contained within a shared Bioinformatics Resource for data mining by the wider scientific community. In addition one of the major goals of this project is to develop of new analytical tools for determining and altering the expression of all members of the nuclear receptor family in specific cells and tissues. In addition, we will design, develop and validate a comprehensive lentiviral shRNA knockdown library that targets the entire NR family. Finally, we will use the library to interrogate cell lines and animal models of metabolic, inflammatory and cancer states in which a receptor has been shown to have a dynamic and/or dominant expression profile. The NR lentiviral shRNA knockdown library will be made available other NURSA members with the eventual goal of supplying the research community with a powerful new tools for analyzing NR function.