Expression Profiling in Physiologic and Pathophysiologic Processes

生理和病理生理过程中的表达谱

• 批准号: 7350607
• 负责人: DAVID J MANGELSDORF
• 金额: $ 39.12万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7350607
• 关键词: ATP-Binding Cassette Transporters; Age; Aging; Biological Assay; Communities; Cytochromes; Data; Databases; Diagnosis; Diagnostic; Disease; Funding; Gene Family; Gene Targeting; Genes; Genetic; Goals; Harvest; Hepatitis; Human; Individual; Leptin; Ligands; Lung; Malignant Neoplasms; Malignant neoplasm of lung; Measures; Metabolic Diseases; Metabolic syndrome; Methods; MicroRNAs; Molecular Profiling; Mus; Nuclear Receptors; Online Systems; Patients; Physiological; Polymerase Chain Reaction; Process; Relative (related person); Resources; Sampling; Therapeutic; Time; Tissues; Wild Type Mouse; Work; base; human disease; mRNA Expression; malignant breast neoplasm; mouse model; non-alcoholic; prognostic; receptor expression; success

The long-term objectives of this application are to utilize expression profiling of nuclear receptors and their associated co-regulators and target genes to answer fundamental questions about various physiologic and pathophysiologic processes, including diseases associated with metabolic syndrome, cancer, and aging. Our hypothesis is that NRs represent a principle component set of expressed genes that have the predictive power to provide diagnostic, prognostic, and therapeutic information on an individual basis. An equally important goal of this work is to provide a web-based database that contains this expression profiling information as a mineable resource to the scientific community. Following on the success of the previous funding period to establish a high-throughput, quantitative real-time PCR method for assaying nuclear receptor expression, we plan the following three specific aims: 1) NR expression profiling from human patient samples with various metabolic diseases and cancer. We will use QPCR to measure nuclear receptor (NR) and coregulator (CoR) mRNA expression in samples from patients with non-alcoholic steatosis hepatitis (NASH), and lung and breast cancers. 2) NR expression profiling in mouse models of metabolic diseases and aging. We plan to use both dietary and genetic approaches to assess the dynamics of NR and CoR mRNA expression in tissues collected from wild-type and ob/ob mice treated with NR ligands, as well as in wild-type mice over the course of aging. 3) Expression profiling of additional gene families that correlate to NR expression. We will apply the same standardized QPCR profiling assays to measure the ATP-binding cassette transporters (ABCs), cytochrome p450s (p450s), and microRNAs (miRNAs). Previous data have shown these gene families are either effectors and/or primary targets of NR action. Samples harvested during the previous funding period and those acquired as part of Aims 1 and 2 will be interrogated. Together with other components of the NURSA consortium, these aims should provide an invaluable resource to the NR field, and establish new translational methods for diagnosing and treating human disease.

该应用的长期目标是利用核受体及其的表达分析 相关的共同调节因子和靶基因，以回答有关各种生理和 病理生理过程，包括与代谢综合征，癌症和衰老有关的疾病。我们的 假设是NRS代表具有预测性的原理成分集 单独提供诊断，预后和治疗信息的能力。同样 这项工作的重要目标是提供一个基于Web的数据库，该数据库包含此表达式分析 信息作为科学界的可赚钱资源。跟随以前的成功 建立高通量，定量实时PCR方法的资金期限用于测定核 受体表达，我们计划以下三个特定目的：1）来自人类患者的NR表达分析 样品患有各种代谢疾病和癌症。我们将使用QPCR测量核受体（NR） 来自非酒精性脂肪变性肝炎患者的样品中的核心节（COR）mRNA表达 （纳什），肺和乳腺癌。 2）代谢性疾病的小鼠模型中的NR表达分析 和老化。我们计划使用饮食和遗传方法来评估NR和COR的动力学 从用NR配体处理的野生型和OB/OB小鼠收集的组织中的mRNA表达，以及 在衰老过程中，野生型小鼠。 3）相关的其他基因家族的表达分析 NR表达。我们将应用相同的标准化QPCR分析测定法来测量ATP结合 盒式转运蛋白（ABC），细胞色素P450（P450）和microRNA（miRNA）。以前的数据具有 显示这些基因家族是NR作用的效应子和/或主要靶标。样品收获 在上一个资金期间以及作为目标1和2的一部分获得的资金将受到审问。一起 与NERTA财团的其他组成部分，这些目标应为其提供宝贵的资源 NR领域，并建立新的翻译方法来诊断和治疗人类疾病。