FUNCTIONAL GENOMICS & VIROLOGY CORE

在功能基因组学和病毒学核心中，我们汇集了NIH资助的不同群体， 来自基础科学和临床医学的研究人员。这些研究人员有一个共同的兴趣， 最先进的技术，以更好地了解进展背后的分子机制 从HCV感染到终末期肝病。该中心在定义全球基因方面取得了巨大进展 与HCV感染相关的表达特征，包括基因表达模式的鉴定 特别是与纤维化进展相关。虽然该中心继续利用复发的HCV后， 肝移植作为一种研究工具，我们现在更加重视艾滋病，包括 HCV/HIV-1共感染和体外HIV感染系统。我们还开始与 万年青治疗服务调查静脉药物滥用对HCV相关肝脏的影响 疾病和治疗。本核心的具体目标是：1）提供生物样本，包括临床样本， 体外和动物模型系统，用于微阵列、蛋白质组学和分子病毒学分析。支持 服务将包括样品制备，RNA和蛋白质分离，以及基因组材料的制备。 和蛋白质组学分析。用于HCV感染的模型系统将包括但不限于SCIDbeige/ Alb-uPA小鼠模型和HCV 2a体外感染系统。有关爱滋病的研究将包括 分析来自HCV和HIV-1共感染患者和来自体外HIV-1感染患者的肝活检， 体内SIV感染系统。2)使用寡核苷酸微阵列，蛋白质组学，激光/共聚焦显微镜， 和分子病毒学来描述在HCV感染，HCV/HIV-1合并感染， 以及肝病和艾滋病的进展。该核心的总体目标是拥有一个集成的系统， 利用基因组学工具和经典的生物学方法来了解宿主对病毒感染的反应 病毒学和组织学测定。我们将基因表达数据（本核心）与蛋白质组学整合的能力 数据（蛋白质组学核心）和复杂的生物信息学技术（生物信息学和生物统计学核心）将 提供深入了解与肝病和艾滋病相关的分子机制。最终，这将 通过产生改进的诊断方法、疾病进展的标志物和新的 治疗干预的方法。

In the Functional Genomics & Virology Core, we have brought together a diverse group of NIH-funded investigators from basic science and clinical medicine. These investigators have a common interest in using state-of-the-art technologies to better understand the molecular mechanisms underlying the progression from HCV infection to end-stage liver disease. The Center has made great strides in defining global gene expression signatures associated with HCV infection, including the identification of gene expression patterns specifically associated with fibrosis progression. While the Center continues to exploit recurrent HCV after liver transplantation as an investigative tool, we now include a greater emphasis on AIDS, including HCV/HIV-1 co-infection and in vitro HIV infection systems. We have also initiated collaborations with Evergreen Treatment Services to investigate the impact of intravenous drug abuse on HCV-associated liver disease and treatment. The Specific Aims of this Core are to: 1) Supply biological samples, including clinical, in vitro and animal model systems, for microarray, proteomic, and molecular virological analysis. Support services will include sample preparation, RNA and protein isolation, and preparation of materials for genomic and proteomic analyses. Model systems for HCV infection will include, but not be limited to, the SCIDbeige/ Alb-uPA mouse model and the HCV 2a in vitro infection system. AIDS-related studies will include the analysis of liver biopsies from patients co-infected with HCV and HIV-1 and from in vitro HIV-1 infection and in vivo SIV infection systems. 2) Use oligonucleotide microarrays, proteomics, laser/confocal microscopy, and molecular virology to profile the cellular events that occur during HCV-infection, HCV/HIV-1 co-infection, and liver disease and AIDS progression. The overall goal of this Core is to have an integrated systems biology approach to understand the host response to virus infection utlizing genomics tools and classical virological and histological assays. Our ability to integrate gene expression data (this Core) with proteomic data (Proteomics Core) and sophisticated bioinformatic techniques (Bioinformatics & Biostatistics Core) will provide insight into the molecular mechanisms associated with liver disease and AIDS. Ultimately, this will improve patient care by yielding improved diagnostic methods, markers of disease progression, and novel approaches for therapeutic intervention.