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
基本信息
- 批准号:10364288
- 负责人:
- 金额:$ 55.43万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 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:
- 关键词:AccountingAcuteAddressBacteremiaBacteriaBioinformaticsBiologicalBiological MarkersBlood TestsBlood specimenCardiovascular DiseasesCause of DeathCessation of lifeClinicalComplexCoupledDataData SetDevelopmentDiabetes MellitusDiagnosisDiagnosticDiseaseDoseEarly DiagnosisEarly treatmentEscherichia coliEvaluationFoundationsFunctional disorderFutureGoalsHospital CostsHumanImmune responseImmune systemImmunoassayInfectionInfrastructureLifeMalignant NeoplasmsMass Spectrum AnalysisMethodsMissionModelingMonitorNational Institute of General Medical SciencesOklahomaOrganPapioPathologistPatientsPlasmaPositioning AttributePrognosisProteomeProteomicsPublic HealthRaceResearchResourcesSamplingScientistSepsisSeptic ShockSepticemiaSourceSpecialistStandardizationStaphylococcus aureusSyndromeTestingTherapeuticTimeTissue SampleTranslatingValidationbasebiomarker developmentbiomarker discoverybiomarker panelbiomarker signaturebiomarker validationcandidate markerclinical developmentcohortcomorbiditydifferential expressiondrug developmentearly detection biomarkersexperienceexperimental studyimproved outcomeinstrumentationmedical attentionmicrobialmultidisciplinarynonhuman primatenovelnovel markernovel therapeuticspathogenpatient stratificationperformance testspersonalized medicinepredictive markerprotein biomarkersproteomic signatureresearch clinical testingseptic patientsspecific biomarkersstatisticstargeted treatmenttooltreatment strategyvalidation studies
项目摘要
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.
抽象的
该项目将使用基于质谱的蛋白质组学来发现和验证生物标志物,并将
对可能构成基础的强大候选生物标志物和生物标志物特征进行早期评估
用于新的临床血液测试。这些生物标志物可用作早期检测败血症和/或
促进脓毒症治疗方法的临床开发。
目标:本应用的重点是鉴定和初步生物学、分析和临床
评估脓毒症的生物标志物和生物标志物特征,为最终的分析和临床做好准备
验证。
中心假设:使用来自标准化良好的非人类灵长类动物的血液样本发现蛋白质组学
脓毒症模型随后在临床样本中进行验证有可能揭示新的生物标志物和生物标志物
用于脓毒症患者早期检测、预后和治疗监测的面板。
理由:脓毒症是一种复杂的异质性疾病,经常伴有合并症(例如,
癌症、糖尿病、心血管疾病),它们可以改变宿主对病原体的反应,从而使其变得困难
通过临床血浆样本中的发现蛋白质组学来确定脓毒症特异性生物标志物谱。我们
建议使用公正的蛋白质组学,结合强大的生物信息学来发现新的预测生物标志物。
我们处于实现这些目标的独特位置,可以从以下来源获得经过充分表征的血浆样本
使用革兰氏阴性或革兰氏阳性菌血症的狒狒模型进行历史时间过程实验 -
加上配备世界一流仪器的 NIGMS 国家蛋白质组学资源
专业知识。此外,定量蛋白质组学和免疫测定将用于鉴定和验证
脓毒症患者血浆中的新型生物标志物。
具体目标 1: 早期生物标志物的鉴定和器官图谱
狒狒实验性败血症。
具体目标 2:临床样本中候选生物标志物的验证和性能测试。
影响:我们的短期目标是确定狒狒和狒狒败血症的生物标志物和生物标志物特征
使用精心标准化的样本对人体进行初步生物学、分析和临床评估
和数据集。我们项目的长期目标是提供新的候选生物标志物,为
明确的分析和临床验证研究。这些生物标志物将有助于早期诊断和监测
脓毒症进展并将有助于患者分层进行靶向治疗。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
FLOREA LUPU其他文献
FLOREA LUPU的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('FLOREA LUPU', 18)}}的其他基金
COBRE: OK MED RES FOUND: CORE I: IN VITRO MICROSCOPY CORE
COBRE:确定医学研究成果:核心 I:体外显微镜核心
- 批准号:
8168454 - 财政年份:2010
- 资助金额:
$ 55.43万 - 项目类别:
EPCR, TAFI as Regulators of PMN/Endothelial Interaction
EPCR、TAFI 作为 PMN/内皮相互作用的调节剂
- 批准号:
7939125 - 财政年份:2009
- 资助金额:
$ 55.43万 - 项目类别:
相似海外基金
Acute senescence: a novel host defence counteracting typhoidal Salmonella
急性衰老:对抗伤寒沙门氏菌的新型宿主防御
- 批准号:
MR/X02329X/1 - 财政年份:2024
- 资助金额:
$ 55.43万 - 项目类别:
Fellowship
Transcriptional assessment of haematopoietic differentiation to risk-stratify acute lymphoblastic leukaemia
造血分化的转录评估对急性淋巴细胞白血病的风险分层
- 批准号:
MR/Y009568/1 - 财政年份:2024
- 资助金额:
$ 55.43万 - 项目类别:
Fellowship
Combining two unique AI platforms for the discovery of novel genetic therapeutic targets & preclinical validation of synthetic biomolecules to treat Acute myeloid leukaemia (AML).
结合两个独特的人工智能平台来发现新的基因治疗靶点
- 批准号:
10090332 - 财政年份:2024
- 资助金额:
$ 55.43万 - 项目类别:
Collaborative R&D
Cellular Neuroinflammation in Acute Brain Injury
急性脑损伤中的细胞神经炎症
- 批准号:
MR/X021882/1 - 财政年份:2024
- 资助金额:
$ 55.43万 - 项目类别:
Research Grant
STTR Phase I: Non-invasive focused ultrasound treatment to modulate the immune system for acute and chronic kidney rejection
STTR 第一期:非侵入性聚焦超声治疗调节免疫系统以治疗急性和慢性肾排斥
- 批准号:
2312694 - 财政年份:2024
- 资助金额:
$ 55.43万 - 项目类别:
Standard Grant
Combining Mechanistic Modelling with Machine Learning for Diagnosis of Acute Respiratory Distress Syndrome
机械建模与机器学习相结合诊断急性呼吸窘迫综合征
- 批准号:
EP/Y003527/1 - 财政年份:2024
- 资助金额:
$ 55.43万 - 项目类别:
Research Grant
FITEAML: Functional Interrogation of Transposable Elements in Acute Myeloid Leukaemia
FITEAML:急性髓系白血病转座元件的功能研究
- 批准号:
EP/Y030338/1 - 财政年份:2024
- 资助金额:
$ 55.43万 - 项目类别:
Research Grant
KAT2A PROTACs targetting the differentiation of blasts and leukemic stem cells for the treatment of Acute Myeloid Leukaemia
KAT2A PROTAC 靶向原始细胞和白血病干细胞的分化,用于治疗急性髓系白血病
- 批准号:
MR/X029557/1 - 财政年份:2024
- 资助金额:
$ 55.43万 - 项目类别:
Research Grant
ロボット支援肝切除術は真に低侵襲なのか?acute phaseに着目して
机器人辅助肝切除术真的是微创吗?
- 批准号:
24K19395 - 财政年份:2024
- 资助金额:
$ 55.43万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Collaborative Research: Changes and Impact of Right Ventricle Viscoelasticity Under Acute Stress and Chronic Pulmonary Hypertension
合作研究:急性应激和慢性肺动脉高压下右心室粘弹性的变化和影响
- 批准号:
2244994 - 财政年份:2023
- 资助金额:
$ 55.43万 - 项目类别:
Standard Grant