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Multiplex Mass Spectrometric Protein Assays for Precise Monitoring of the Pathophysiology of Obesity

用于精确监测肥胖病理生理学的多重质谱蛋白质分析

基本信息

批准号：
10238054
负责人：
Wei-Jun Qian
金额：
$ 75.28万
依托单位：
BATTELLE PACIFIC NORTHWEST LABORATORIES
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-20 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10238054
关键词：
Adopted Adult Affinity Anti-Inflammatory Agents Area Benchmarking Biochemistry Biological Assay Biological Markers Blinded Blood Proteins Body Weight decreased Buffaloes C-reactive protein Cardiovascular Diseases Child Clinical Collaborations Communities Coupled Data Detection Diabetes Mellitus Disease Epidemic Failure Family Functional disorder GDF15 gene Goals Hormones IGF1 gene Immunoassay Inflammatory Insulin Insulin Resistance Insulin-Like Growth-Factor-Binding Proteins Intelligence Intervention LCN2 gene Laboratories Leptin Mass Spectrum Analysis Matrix Metalloproteinases Medicine Metabolism Monitor Non-Insulin-Dependent Diabetes Mellitus Obesity Overweight Patient Care Peptides Performance Phase Plasma Prevalence Procedures Protein Isoforms Proteins Protocols documentation RBP4 gene Reagent Reporting Reproducibility Research Research Institute Resolution Sampling Site Solid Specificity Standardization Technology Translational Research Translations Universities Validation Vermont Weight Work adipokines adiponectin assay development base biomarker panel blood glucose regulation cancer type clinical application cohort combat data repository disorder prevention energy balance experience experimental study ghrelin inflammatory marker insight mortality risk multiplex assay multiplex detection obese person personalized care personalized medicine precision medicine pressure prohormone resistance exercise validation studies

项目摘要

PROJECT SUMMARY/ABSTRACT The prevalence of overweight and obesity has increased dramatically in recent decades in both children and adults, reaching an epidemic proportion. In order to gain new insights into the pathophysiology of obesity towards better personalized patient care, there is a critical need to develop reliable multiplex protein assays that can be easily implemented in clinical laboratories to enable precise monitoring of many hormones and inflammatory markers closely associated with obesity. Unfortunately, current clinical assays often lack of reproducibility, especially between different clinical laboratories due to the lack of assay standardization. Targeted mass spectrometry is a promising technology for providing robust multiplex assays for blood proteins. Therefore, the overall objective of this application is to develop and validate reproducible and transferable mass spectrometry-based multiplex protein assays for enabling precise quantification of a panel of obesity markers. The panel will cover multiple aspects of obesity pathophysiology, including glucose homeostasis and energy balance (e.g., insulin, leptin, and other hormones), pro-inflammatory markers (e.g., C-reactive protein), and anti-inflammatory markers (e.g., adiponectin). To facilitate full validation of the robustness and transferability of the assays, an inter-lab assay validation will be pursued. Specifically, Aim 1 will be focused on initial assay development for optimal configurations and on demonstrating confident multiplex detection of endogenous analytes in blood plasma. Aim 2 will be centered on assay optimization and full assay characterization in the aspects of reproducibility, stability, selectivity, linearity, and limit of quantification. Aim 3 will demonstrate the utility of the assays through inter-lab quantification of endogenous analytes in a pilot cohort of clinical plasma samples from normal weight and obese subjects, and obese individual before and after weight loss and benchmarking against well-established immunoassays for selected analytes such as insulin and leptin. To facilitate the easy- implementation of the validated assays in other laboratories, all assay data including chromatographic data and detailed standard operating procedures will be shared through public data repositories and assay portals. Together, the project will establish robust and easy-to-transfer multiplex assays that will enable precise monitoring of the pathophysiology of obesity.

项目总结/文摘