Core D: Biomarkers, Genomics & Epigenomics Core

BGE核心概述：生物标志物、基因组和表观基因组学(BGE)核心的目标是促进 并协调WNY调味品研究中心内的1-3个项目的生物谱学分析 烟草制品(克罗夫特)，以加强整体主题和提高科学生产力。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(完)/雪茄/水烟斗烟草和确定生物标志物 在生物体液、原代细胞和组织中的暴露和潜在危害。这些同步的努力将会增加 关于加香烟草产品的有效性和确保有效、高精度的规程和可重复使用的方法 适用于FDA-CTP的监管需求。我们提供的证据表明 暴露于空气和烟草/香烟烟雾(CS)的小鼠和 人类非吸烟者与吸烟者经Luminex、ELISA、质谱学、基因组学和 表观基因组学方法。我们意识到加香烟草产品会影响系统性生物标记物 潜在危害，包括将在具体目标1-3下调查的基因组和表观基因组签名： 目标1：标准化实验条件，重点是实验室检测、生化分析和 测量接触加香烟草潜在危害的生物标记物的分析方法 产品。我们将从项目(1-3)中获取生物检疫/样本，以分析暴露和 潜在危害(毒性)，包括标准生化分析。此外，BGE核心将支持人类 研究以核实烟草产品在血浆、唾液和尿样中的尼古丁摄入量和暴露状况。 目标2：开发标准生物测定以确定现有的/已知的和较新的循环生物标记物 使用基因组和表观基因组的生物液、原代细胞和临床前小鼠模型 接近了。我们将评估现有的生物标记物，并开发新的鉴定方法 使用尖端基因组学和 用表观基因组学方法指导调味烟草制品的监管。 目的3：建立基于毒性/生物评价的多元毒性分级系统 加味烟草产品的影响/健康结果。我们将开发出一种多元毒性 基于潜在危害的生物标记物、基因组和表观基因组签名的排名系统 BGE核心以及BI(生物统计和信息学)核心的参与，以进行深入的生物统计 分析。BGE CORE的总体目标是提供测试生物标记物所需的新技术 生物体液、原代细胞和临床前模型。BGE核心将为发展和发展提供核心资源 根据良好实验室操作规范(GLP)标准进行的分析性能，以告知FDA的 对香料烟草产品的生产、分销和营销进行监管，以保护公众健康。

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.