Center for Novel Biomarkers of Response

新型反应生物标志物中心

• 批准号: 7851507
• 负责人: Joel G Pounds
• 金额: $ 146万
• 依托单位: BATTELLE PACIFIC NORTHWEST LABORATORIES
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-15 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7851507
• 关键词: Center; Novel; Biomarkers; Response

The ultimate goal of the Exposure Biology Program is to understand the development and progression of complex disease by precisely, accurately, and quantitatively assessing the individual's exposure to environmental stressors and the individual's responses to these stressors. Two of the most important risk factors for human morbidity and mortality are exposure to cigarette smoke and obesity, both assocaiated with systemic chronic inflammation and oxidative stress. The organizing theme the Center is that identification and validation of persistent modified proteins in plasma will provide specific information about the stressor, its mode of action, and the target organ. The environmental stress of the human and animal projects is focused on main-stream and side-stream cigarette smoke with obesity as a confounding physiological factor. We propose an integrated, multidisciplinary center with three research projects (human, mouse, and sensor) and two technology cores (proteomics and ELISA Microarray) which collectively will have four goals. Aim 1. Discover reactive nitrogen and reactive oxygen species (RNS/ROS) modified peptides using MS/MS as candidate biomarkers. Aim 2. Verification of RNS/ROS modified peptides as specific biosignatures using data-directed MS. Aim 3. Validation of RNS/ROS modified proteins for use as specific biomarkers for environmental stressors using custom-designed sandwich ELISA microarrays. Aim 4. Develop, test, and deploy two detector systems for exposure and for both specific and general markers of RNS/ROS response. A laboratory-based ELISA Microarray platform will be used to provide high-throughput, multiplexed analysis of dozens of analytes. The validated biomarkers will be also be deployed on a prototype, clinic-deployable detector system for on-site analysis. The sensor system is nanoparticle-based multiplexed Immunochromatographic / Electrochemical Biosensor (IEB) that will support the measurement of markers for exposure (cotinine) and response, both specific (modified proteins) and generic markers of oxidative stress and chronic inflammation, such as TNF-alpha, in a single platform. Critical Outcomes and Deliverables. The PNNL U54 Center will apply state-of-the-art proteomic and sensor technologies to provide NIEHS with a database of mode-of-action informing biomarkers of response, reagents for selected markers tested and validated in humans and informed by parallel studies in mice, and deployed on (a) a laboratory based ELISA Microarray platform, and (b) on a robust, clinic-deployable nanoparticle-based sensor suitable for use in large-scale human biomonitoring studies to evaluate the interaction of genes and the environment. The results of this U54 Center also will improve the scientific community's ability to compare, contrast and extrapolate biomarkers between humans and mice.

暴露生物学项目的最终目标是通过精确、准确和定量地评估个体暴露于环境压力源和个体对这些压力源的反应来了解复杂疾病的发展和进展。人类发病和死亡的两个最重要的危险因素是吸烟和肥胖，两者都与全身性慢性炎症和氧化应激有关。该中心的组织主题是，血浆中持久性修饰蛋白的鉴定和验证将提供有关应激源、其作用方式和靶器官的具体信息。人类和动物项目的环境压力主要集中在主流和侧流吸烟，肥胖是一个混杂的生理因素。我们建议建立一个综合的多学科中心，包括三个研究项目（人类、小鼠和传感器）和两个技术核心（蛋白质组学和ELISA微阵列），它们将共同实现四个目标。目的1。利用MS/MS发现活性氮和活性氧（RNS/ROS）修饰的肽作为候选生物标志物。目标2。使用数据导向ms验证RNS/ROS修饰肽作为特异性生物标记使用定制设计的夹心ELISA微阵列验证RNS/ROS修饰蛋白作为环境应激源特异性生物标志物的应用。目标4。开发、测试和部署两种检测系统，用于暴露和RNS/ROS反应的特定和一般标记。基于实验室的ELISA微阵列平台将用于提供高通量，

项目成果

Impaired transcriptional response of the murine heart to cigarette smoke in the setting of high fat diet and obesity.

在高脂肪饮食和肥胖的情况下，小鼠心脏对香烟烟雾的转录反应受损。

• DOI: 10.1021/tx400078b
• 发表时间: 2013
• 期刊: Chemical research in toxicology
• 影响因子: 4.1
• 作者: Tilton,SusanC;Karin,NormanJ;Webb-Robertson,Bobbie-JoM;Waters,KatrinaM;Mikheev,Vladimir;Lee,KMonica;Corley,RichardA;Pounds,JoelG;Bigelow,DianaJ
• 通讯作者: Bigelow,DianaJ

Apoferritin protein nanoparticles dually labeled with aptamer and horseradish peroxidase as a sensing probe for thrombin detection.

• DOI: 10.1016/j.aca.2012.10.041
• 发表时间: 2013-01
• 期刊: Analytica chimica acta
• 影响因子: 6.2
• 作者: Jie Zhao;Meiling Liu;Youyu Zhang;Haitao Li;Yuehe Lin;S. Yao

Disruption of phospholipid and bile acid homeostasis in mice with nonalcoholic steatohepatitis.

• DOI: 10.1002/hep.25630
• 发表时间: 2012-07
• 期刊: Hepatology (Baltimore, Md.)
• 作者: Tanaka N;Matsubara T;Krausz KW;Patterson AD;Gonzalez FJ
• 通讯作者: Gonzalez FJ

Improved quality control processing of peptide-centric LC-MS proteomics data.

• DOI: 10.1093/bioinformatics/btr479
• 发表时间: 2011-10-15
• 期刊: Bioinformatics (Oxford, England)
• 作者: Matzke MM;Waters KM;Metz TO;Jacobs JM;Sims AC;Baric RS;Pounds JG;Webb-Robertson BJ
• 通讯作者: Webb-Robertson BJ

Sensitive immunosensor for cancer biomarker based on dual signal amplification strategy of graphene sheets and multienzyme functionalized carbon nanospheres.

• DOI: 10.1021/ac100036p
• 发表时间: 2010-04-01
• 期刊: ANALYTICAL CHEMISTRY
• 影响因子: 7.4
• 作者: Du, Dan;Zou, Zhexiang;Shin, Yongsoon;Wang, Jun;Wu, Hong;Engelhard, Mark H.;Liu, Jun;Aksay, Ilhan A.;Lin, Yuehe
• 通讯作者: Lin, Yuehe