Core D: Biomarkers, Genomics & Epigenomics Core

核心 D：生物标志物、基因组学

基本信息

批准号：
10248513
负责人：
Isaac Kirubakaran Sundar
金额：
$ 62.7万
依托单位：
ROSWELL PARK CANCER INSTITUTE CORP
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-14 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10248513
关键词：
4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol Affect Air Animal Model Awareness Behavior Biochemical Biological Biological Assay Biological Markers Biometry Cells Clinical Communication Cotinine DNA Methylation Electronic Nicotine Delivery Systems Electronic cigarette Ensure Enzyme-Linked Immunosorbent Assay Epithelial Cells Experimental Designs Experimental Models Exposure to Flavoring Genomics Goals Health Human In Vitro Informatics Intake Laboratories Liquid substance Marketing Mass Spectrum Analysis Measures Mediating Methodology Methods Methylation Mus Nasal Epithelium Nicotine Outcome Outcome Measure Performance Plasma Pre-Clinical Model Primary Cell Cultures Productivity Protocols documentation Public Health Quality Control Regulation Reproducibility Research Resource Development Resources Risk Assessment Roswell Park Cancer Institute Saliva Sampling Smoker Smoking Standardization System Technology Testing Tissues Tobacco Toxic effect Training Universities Urine analytical method analytical tool base cigarillos circulating biomarkers cost epigenomics exosome exposure to cigarette smoke extracellular vesicles good laboratory practice hookah in vivo innovation mouse model multidisciplinary nano-string new technology non-smoker novel novel marker pre-clinical predictive marker respiratory health response synergism tobacco advertising tobacco flavor tobacco products tool transcriptome sequencing transcriptomics

项目摘要

BGE CORE SUMMARY: The goal of the Biomarkers, Genomics and Epigenomics (BGE) Core is to facilitate and co-ordinate biospecimen analysis across Projects 1-3 within the WNY Center for Research on Flavored Tobacco Products (CRoFT) to strengthen the overall themes and enhance scientific productivity. The main focus of the BGE core is to provide centralized workflow standards for in vitro and in vivo exposure from electronic nicotine delivery systems (ENDS)/cigarillos/waterpipe tobacco and to determine biomarkers of exposure and potential harm in biofluids, primary cells and tissues. These synchronized efforts will increase efficacy and ensure valid, high precision protocols and reproducible methods around flavored tobacco products suitable for the regulatory needs of the FDA-CTP. We have provided evidence that shows altered systemic biomarkers, genomic and epigenomic signatures in air vs. tobacco/cigarette smoke (CS) exposed mouse and human non-smokers vs. smokers confirmed by luminex, ELISA, mass spectrometry, genomics and epigenomics approaches. We are aware that flavored tobacco products can affect systemic biomarkers of potential harm including genomic and epigenomic signatures that will be investigated under specific aims 1-3: Aim 1: Standardize experimental conditions, focusing on laboratory testing, biochemical assays and analytical methods to measure biomarkers of potential harm from exposure to flavored tobacco products. We will obtain biospecimens/samples from Projects (1-3) to analyze for biomarkers of exposure and potential harm (toxicity) including standard biochemical assays. In addition, BGE core will support the human studies to verify the nicotine intake, exposure status of tobacco products in plasma, saliva and urine samples. Aim 2: Develop standard bioassays to identify existing/known and newer circulating biomarkers in biological fluids, primary cells and pre-clinical mouse models using genomic and epigenomic approaches. We will assess existing biomarkers as well as develop methods for identification of novel biomarkers (extracellular vesicle/exosomes) of exposure/potential harm using cutting-edge genomics and epigenomics approaches to guide regulation of flavored tobacco products. Aim 3: Develop a multivariate toxicity ranking system based on the assessment of toxicity/biological effects/health outcomes measured from flavored tobacco products. We will develop a multivariate toxicity ranking systems based on biomarkers of potential harm, genomic and epigenomic signatures assessed by the BGE core along with the involvement of BI (Biostatistics and Informatics) core for in-depth biostatistical analysis. The overall goal of BGE core is to provide novel technologies needed for testing biomarkers in the biofluids, primary cells and pre-clinical models. BGE core will provide a central resource for development and performance of assays as per good laboratory practice (GLP) standards relevant for informing the FDA’s regulation of the manufacture, distribution and marketing of flavored tobacco products to protect public health.

BGE 核心摘要：生物标志物、基因组学和表观基因组学 (BGE) 核心的目标是促进协调 WNY 风味研究中心项目 1-3 的生物样本分析烟草产品（CRoFT）以强化总体主题和提高科学生产力为主。 BGE 核心的重点是为体外和体内暴露提供集中的工作流程标准电子尼古丁输送系统 (ENDS)/小雪茄/水烟烟草并确定生物标志物这些同步努力将会增加生物体液、原代细胞和组织的暴露和潜在危害。功效并确保调味烟草产品有效、高精度的方案和可重复的方法适合 FDA-CTP 的监管需求，我们提供的证据表明系统发生了变化。空气中的生物标志物、基因组和表观基因组特征与暴露于烟草/香烟烟雾 (CS) 的小鼠和通过 luminex、ELISA、质谱、基因组学和技术证实人类非吸烟者与吸烟者的比较我们知道调味烟草产品可以影响全身生物标志物。潜在危害，包括将在具体目标 1-3 下进行调查的基因组和表观基因组特征：目标1：标准化实验条件，重点关注实验室检测、生化检测和测量接触调味烟草潜在危害的生物标志物的分析方法我们将从项目 (1-3) 获取生物样本/样本，以分析暴露和生物标志物。潜在危害（毒性），包括标准生化检测此外，BGE 核心将支持人类。研究验证尼古丁摄入量以及血浆、唾液和尿液样本中烟草制品的暴露状况。目标 2：开发标准生物测定法来识别现有/已知和更新的循环生物标志物使用基因组和表观基因组的生物液体、原代细胞和临床前小鼠模型我们将评估现有的生物标志物并开发识别新生物标志物的方法。使用尖端基因组学和暴露/潜在危害的生物标志物（细胞外囊泡/外泌体）表观基因组学方法指导调味烟草产品的监管。目标 3：开发基于毒性/生物学评估的多变量毒性排名系统通过调味烟草产品测量的影响/健康结果我们将开发多变量毒性。基于潜在危害的生物标志物、基因组和表观基因组特征的排名系统 BGE核心以及BI（生物统计和信息学）核心的参与，进行深入的生物统计 BGE 核心的总体目标是提供测试生物标志物所需的新技术。生物流体、原代细胞和临床前模型将为开发和提供核心资源。根据与 FDA 相关的良好实验室规范 (GLP) 标准进行检测对调味烟草产品的制造、分销和营销进行监管，以保护公众健康。