基于质谱的生物标志物发现-猫眼课题宝

基于质谱的生物标志物发现

批准号：

8267662

负责人：

Subramaniam Pennathur

金额：

$38.24万

依托单位：

UNIVERSITY OF MICHIGAN AT ANN ARBOR

依托单位国家：

美国

项目类别：

财政年份：

2009

资助国家：

美国

项目状态：

已结题

起止时间：

2009-08-07 至 2015-05-31

来源：

https://reporter.nih.gov/project-details/8267662

关键词：

3-chlorotyrosine 3-nitrotyrosine Acetylcysteine Acute Acute respiratory failure Address Affect Alveolar Amino Acids Ancillary Study Antioxidants Apoptosis Applications Grants Area Azathioprine Biological Markers Blood capillaries Carbon Monoxide Cells Cessation of life Chronic Chronic Obstructive Airway Disease Clinical Clinical Research Clinical Trials Clinical Trials Network Cross-Sectional Studies Data Development Diagnosis Diagnostic Diffuse Disease Disease Progression Effectiveness Enrollment Epithelial Cells Fibrosis Frequencies Gases Glutathione Goals Hamman-Rich syndrome Heterogeneity Human Incidence Individual Inflammatory Laboratories Lung diseases Mass Fragmentography Mass Spectrum Analysis Measures Mediating Molecular Profiling Morbidity - disease rate Multi-Institutional Clinical Trial Myofibroblast Natural regeneration Oral Outcome Oxidation-Reduction Oxidative Stress Oxidative Stress Pathway Parents Pathogenesis Pathway interactions Patients Performance Pharmaceutical Preparations Pharmacotherapy Phase III Clinical Trials Physiological Placebos Plasma Plasma Proteins Post-Translational Protein Processing Prednisone Prevalence Progressive Disease Protein Profiling Microarrays Proteins Proteome Proteomics Randomized Reactive Nitrogen Species Reactive Oxygen Species Request for Applications Respiratory Failure Respiratory physiology Risk Role Sampling Severities Severity of illness Signal Transduction Stratification Subgroup Techniques Testing Therapeutic Intervention Therapeutic immunosuppression Tissues Tyrosine United States United States National Institutes of Health Vital capacity Volunteer Group Walking abstracting antioxidant therapy base capillary cell injury cell type clinical application clinical phenotype cohort conventional therapy dityrosine drug discovery effective therapy functional loss high risk injury and repair insight lung injury mortality novel novel strategies oxidation protein profiling public health relevance repaired response success treatment strategy volunteer

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DESCRIPTION (provided by applicant): Humans with Idiopathic pulmonary fibrosis (IPF) are at a high risk for progressive respiratory failure, acute exacerbations of the disease and death. There is a recognized need for novel mechanism-based biomarkers that accurately predict pathways activated in the individuals with progressive IPF and those that are likely to be more responsive to specific therapies. This proposal is in response to a request of application (RFA-HL-08- 001) and directly addresses this critical gap in our diagnostic capability. The overall goals of this proposal are to develop and validate novel biomarkers using a mass spectrometry (MS)-based approach followed by a microarray-based proteomic platform combined with MS to elucidate pathways that contribute to IPF progression. A major focus of the proposal will involve development of a microarray-based proteomic platform that can readily be transferred to high throughput clinical applications. Using highly sensitive and specific gas chromatography MS we have recently characterized and validated specific markers of oxidative stress in human plasma. These markers serve as molecular fingerprints for specific oxidation pathways. We have also developed a novel microarray based proteomic platform that can accurately identify and screen modified proteins from the plasma proteome. We predict that using our novel approach we will be able to identify differential oxidation of plasma proteins which uniquely identifies subsets of IPF patients at risk for progressive disease and those likely to benefit from redox-modulating drug therapies. PUBLIC HEALTH RELEVANCE: IPF is a progressive and ultimately fatal disease for which no effective drug therapies currently exist. Finding effective therapies for this disease has been limited by the lack of reliable biomarkers of disease activity/progression. Heterogeneity in responsiveness to specific treatments may also limit the ability to demonstrate effectiveness of a particular treatment strategy. This study will define novel plasma biomarkers in IPF patients with progressive disease and identify specific patient subgroups that respond favorably to redox- modulating drug therapy. (End of Abstract)

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