Discovery and Characterization of Novel Sepsis Proteome Biomarkers

新型脓毒症蛋白质组生物标志物的发现和表征

• 批准号: 10364288
• 负责人: FLOREA LUPU
• 金额: $ 55.43万
• 依托单位: OKLAHOMA MEDICAL RESEARCH FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-10 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10364288
• 关键词: Accounting; Acute; Address; Bacteremia; Bacteria; Bioinformatics; Biological; Biological Markers; Blood Tests; Blood specimen; Cardiovascular Diseases; Cause of Death; Cessation of life; Clinical; Complex; Coupled; Data; Data Set; Development; Diabetes Mellitus; Diagnosis; Diagnostic; Disease; Dose; Early Diagnosis; Early treatment; Escherichia coli; Evaluation; Foundations; Functional disorder; Future; Goals; Hospital Costs; Human; Immune response; Immune system; Immunoassay; Infection; Infrastructure; Life; Malignant Neoplasms; Mass Spectrum Analysis; Methods; Mission; Modeling; Monitor; National Institute of General Medical Sciences; Oklahoma; Organ; Papio; Pathologist; Patients; Plasma; Positioning Attribute; Prognosis; Proteome; Proteomics; Public Health; Race; Research; Resources; Sampling; Scientist; Sepsis; Septic Shock; Septicemia; Source; Specialist; Standardization; Staphylococcus aureus; Syndrome; Testing; Therapeutic; Time; Tissue Sample; Translating; Validation; base; biomarker development; biomarker discovery; biomarker panel; biomarker signature; biomarker validation; candidate marker; clinical development; cohort; comorbidity; differential expression; drug development; early detection biomarkers; experience; experimental study; improved outcome; instrumentation; medical attention; microbial; multidisciplinary; nonhuman primate; novel; novel marker; novel therapeutics; pathogen; patient stratification; performance tests; personalized medicine; predictive marker; protein biomarkers; proteomic signature; research clinical testing; septic patients; specific biomarkers; statistics; targeted treatment; tool; treatment strategy; validation studies

ABSTRACT This project will use mass spectrometry-based proteomics for biomarker discovery and validation and will perform early evaluation of strong candidate biomarkers and biomarker signatures that might form the foundation for new clinical blood tests. These biomarkers can be used as diagnostic tools for early detection of sepsis and/or facilitate the clinical development of sepsis therapeutics. Objectives: The focus of this application is on the identification and initial biological, analytical and clinical evaluation of biomarkers and biomarker signatures for sepsis that will be ready for definitive analytical and clinical validation. Central hypothesis: Discovery proteomics using blood samples from well-standardized non-human primate sepsis models followed by validation in clinical samples has the potential to reveal new biomarker and biomarker panels for early detection, prognosis and therapy monitoring of sepsis patients. Rationale: Sepsis is a complex, heterogeneous disease that frequently is complicated with comorbidities (e.g., cancer, diabetes, cardiovascular disease) that can alter the host responses to pathogens, thus making it difficult to determine the spectrum of sepsis-specific biomarkers by discovery proteomics in clinical plasma samples. We propose to use unbiased proteomics, coupled with robust bioinformatics to discover novel predictive biomarkers. We are in a unique position to achieve these goals, having access to well-characterized plasma samples from historical time-course experiments using baboon models of Gram-negative or Gram-positive bacteremia – coupled with access to a NIGMS national proteomics resource equipped with world-class instrumentation and expertise. Further, quantitative proteomics and immunoassays will be used for qualification and validation of the novel biomarkers in human plasma from sepsis patients. Specific Aim 1: Identification and organ mapping of early stage biomarkers during the time course of experimental sepsis in baboons. Specific Aim 2: Validation and performance testing of biomarker candidates in clinical samples. Impact: Our short-term goals are to identify biomarkers and biomarker signatures for sepsis in baboons and perform the initial biological, analytical and clinical evaluation in humans using carefully standardized samples and datasets. The long-term goal of our project is to deliver novel candidate biomarkers that are ready for definitive analytical and clinical validation studies. These biomarkers will allow early diagnosis and monitoring of sepsis progression and will help patient stratification for targeted therapies.

摘要