Translational Biomarker Facility Core

翻译生物标志物核心(TBC)：摘要 翻译生物标记物核心(TBC)支持在 战略远景中描述的卓越环境毒理学(CEET)。核心使用生物分析 测量暴露和影响、疾病发生和进展以及治疗的生物标志物的方法 对环境病原学疾病的反应。TBC采用了基于严格的质谱学(MS) 在基于细胞培养的模型、动物模型、人群和患者中识别生物标记物的方法学 在综合健康科学设施核心(IHSFC)中设计的队列研究。所测量的分析物是金属 离子、生物小分子、蛋白质以及靶向和非靶向代谢物 “曝光”。TBC认识到有必要将生物标记物的表型变化与 转录组或带有遗传变异，这是通过暴露执行的数据集成实现的 生物信息学核心(EBIC)。基因组、蛋白质组和代谢组学生物标记物的集成提供了 承诺提供新的诊断和预后指标。我们的目标是将调查结果转化为改进 脆弱人群或个人的环境健康，我们称之为精准公共卫生 (PPH)。TBC配备了最先进的超性能液相色谱(UPLC)-MS和 UPLC-高分辨率(HR)MS仪器。它还配备了电感耦合等离子体(ICP)-MS 用于重金属的形态分析。许多LC-MS分析使用稳定同位素稀释(SID)LC-MS作为 精密度和准确度的黄金标准，许多分析无法在世界其他地方进行。 该核心将实现以下目标。目标1：我们将为CEET提供高度敏感和特异的检测方法 研究人员在模型系统和人群生物体液中分析暴露和影响的生物标志物 队列和病人。在目标2：我们将支持CEET关于空气污染和肺部健康的专题领域； 环境暴露与癌症，易感窗口；环境神经科学与服务 并使用蛋白质组学和代谢组学方法实现生物标记物的发现。目标3：我们将开发新的 对专题领域进行分析，并根据CEET调查人员的需要确定服务的优先顺序。在目标4中：我们将 为试点项目接受者和环境健康科学的初步研究提供分析支持。 目标5：我们将提供使用最先进的分析设备和软件的途径和培训，包括 用于金属分析的新型电感耦合等离子体质谱仪。目标6：我们将把TBC服务与 EBIC和IHSFC使人类主题研究无缝；在目标7：我们将促进生物标记物 通过每月培训班和年度讲习班对CEET调查员及其受训人员进行教育。

TRANSLATIONAL BIOMARKER CORE (TBC): ABSTRACT The Translational Biomarker Core (TBC) supports exposure assessment conducted in the Center of Excellence in Environmental Toxicology (CEET) described in the Strategic Vision. The Core uses bioanalytical methods to measure biomarkers of exposure and effect, disease onset and progression, and therapeutic response for diseases of environmental etiology. The TBC employs rigorous mass spectrometry (MS)-based methodology to identify biomarkers in cell-culture based models, in animal models and in population and patient cohorts studies designed in the Integrative Health Sciences Facility Core (IHSFC). Analytes measured are metal ions, small biomolecules, proteins, as well as targeted and untargeted metabolomes as reporters of the “exposome”. The TBC recognizes the need to relate phenotypic changes in biomarkers with either changes in the transcriptome or with genetic variants and this is achieved by data integration performed by the Exposure Biology Informatics Core (EBIC). The integration of genomic, proteomic and metabolomics biomarkers offers the promise to deliver new diagnostic and prognostic indicators. Our goal is to translate findings to improve environmental health in vulnerable populations or individuals which we call Precision Public Health (PPH). The TBC is equipped with state-of-the art ultraperformance liquid chromatography (UPLC)-MS and UPLC-high resolution (HR) MS instrumentation. It is also equipped with inductively coupled plasma (ICP)-MS for heavy metal analysis with speciation. Many LC-MS assays use stable-isotope dilution (SID) LC-MS as the gold standard for precision and accuracy and many of the assays cannot be performed elsewhere in the world. The Core will perform the following aims. In Aim 1: we will provide highly sensitive and specific assays to CEET investigators to analyze biomarkers of exposure and effect in model systems and in biofluids from population cohorts and patients. In Aim 2: we will support the CEET thematic areas in Air Pollution & Lung Health; Environmental Exposures & Cancer, Windows-of-Susceptibility; and Environmental Neuroscience with services and enable biomarker discovery using proteomics and metabolomics approaches. In Aim 3: we will develop new assays for the thematic areas and prioritize services based on CEET investigators needs. In Aim 4: we will provide analytical support for pilot-project recipients and for preliminary studies in environmental health sciences. In Aim 5: we will provide access and training to use state-of-the art analytical equipment and software, including the new ICP-MS instrument for metal analysis. In Aim 6: we will integrate the TBC services with those of the EBIC and IHSFC so that human subject research is seamless; and in Aim 7: we will facilitate biomarker education for CEET investigators and their trainees through monthly training sessions and annual workshops.