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HUMAN BIOMARKER DISCOVERY AND VALIDATION STUDIES

人类生物标志物的发现和验证研究

基本信息

批准号：
8109313
负责人：
Joel G Pounds
金额：
$ 29.01万
依托单位：
BATTELLE PACIFIC NORTHWEST LABORATORIES
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-06 至 2011-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8109313
关键词：
20 year old Adult Antibodies Arthritis Arts Benchmarking Biological Assay Biological Markers Biology Biosensor Body mass index Breathing Centers for Disease Control and Prevention (U.S.)Cessation of life Child Cholesterol Chronic Chronic Disease Chronic Obstructive Airway Disease Clinic Collaborations Comorbidity Complex Cotinine Custom Data Databases Development Disease Enzyme-Linked Immunosorbent Assay Evaluation Exposure to Fourier transform ion cyclotron resonance Gall Bladder Diseases Generic Drugs Genes Genome Goals Heart Diseases Human Hypertension Individual Inflammation Inflammatory Inflammatory Response Laboratories Measurement Measures Modification Mus National Institute of Environmental Health Sciences Nitrogen Non-Insulin-Dependent Diabetes Mellitus Obesity Organ Outcome Overweight Oxidative Stress Participant Pathway interactions Peptides Plasma Plasma Proteins Population Predisposition Proteins Proteomics Reactive Oxygen Species Reagent Reproducibility Risk Risk Factors Sampling Side Sleep disturbances Smoke Smoker Smoking Source Specificity Stimulus Stream Stress Stroke System Teenagers Testing Tobacco use Toxic Environmental Substances United States United States National Center for Health Statistics Validation aged base biosignature cancer type cigarette smoking cohort cytokine design detector environmental stressor human disease human morbidity mortality multiple reaction monitoring nanoparticle non-smoker programs response response marker sensor stressor tandem mass spectrometry validation studies

项目摘要

The ultimate goal of the Exposure Biology Program is to understand the development and progression of complex disease by 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. Smoking and obesity are each associated with systemic chronic inflammatory and oxidative stress. There is increasing evidence that the oxidative stress resulting from chronic inflammatory stimuli is the unifying mechanism underlying the development of co-morbidities in cigarette smoke and obesity and for the interaction of these risk factors with other environmental toxicants and the genome. We hypothesize that reactive nitrogen and reactive oxygen species (RNS/ROS) modified proteins in plasma will provide important biomarkers for exposure to cigarette smoke, presence of obesity, and the combined response. The overarching objective for Project 1 is to identify, verify, and validate plasma protein biomarkers of oxidative stress in a human population through four aims: Aim 1. Identify RNS/ROS-modified peptides as candidate biomarkers in human plasma using MS/MS. Aim 2 will Verify RNS/ROS-modified peptides as specific biosignatures in 120 human plasma samples by data-directed MS and FTICR-MS (Core A). Aim 3. Validate RNS/ROS-modified proteins for use as specific biomarkers using custom-designed sandwich ELISA microarrays (Core B). The validation will include development and evaluation of antibody reagents and assay reproducibility and sensitivity (Core B). The selection of proteins for validation will be informed by Project 2. Aim 4. Test in the laboratory and in the clinic, a detector system for exposure and for both specific and general markers of RNS/ROS response (with Project 3). The sensor system is nanoparticle-based multiplexed Immunochromatographic / Electrochemical Biosensor (IEB) that will support the measurement of markers for exposure (cotinine) and specific RNS/RNS modified proteins and generic response markers of oxidative stress and chronic inflammation on a single platform. Project 1 will apply state-of-the-art proteomic analysis of human plasma samples from robust, well characterized cohort to provide NIEHS a database of candidate biomarkers, and reagents for selected markers for exposure to cigarette smoke, presence of obesity, and the combined effect. The biomarkers will be tested and validated a cohort containing 500 humans and informed by parallel studies in mice, and deployed on robust, in-clinic deployable nanoparticle-based sensors.

暴露生物学项目的最终目标是了解生物的发展和进步