Human Immunomics & Trained Immunity in Persistent Candidemia
人类免疫组学
基本信息
- 批准号:10551710
- 负责人:
- 金额:$ 43.61万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-08-10 至 2028-05-31
- 项目状态:未结题
- 来源:
- 关键词:ATAC-seqAddressAffectAnti-Infective AgentsAntibiotic TherapyAntibioticsAntifungal TherapyAntigen PresentationAttenuatedAutomobile DrivingBig DataBiological AssayBiometryBlood specimenCandida albicansCandidiasisChIP-seqChromatinClinicalClinical ResearchCoculture TechniquesCommunicable DiseasesComputer AnalysisComputer ModelsDNA MethylationDataDisease OutcomeDisseminated candidiasisEnhancersEnzymesEpigenetic ProcessExperimental ModelsGeneticGenetic TranscriptionGoalsHematogenousHematologyHistone AcetylationHospitalsHumanImmuneImmune Response GenesImmune responseImmune systemImmunityImmunologyIn VitroInfectionInnate Immune ResponseIntegration Host FactorsInterferon Type IIInterferon alphaInterventionLifeLinkMacrophageMapsMediatingMethicillin ResistanceModificationMolecularMulti-Drug ResistanceMusMyeloid CellsNatural ImmunityNitrous OxideOutcomeOxygenPathologicPathway interactionsPatientsPeripheralPhagocytosisPlasmaProphylactic treatmentProteomicsResearchRoleSepsisShapesSignal PathwaySignal TransductionSpecificityStaphylococcus aureusStaphylococcus aureus infectionStimulusSulfidesSurfaceSystemSystems BiologyT cell responseT-Cell ActivationT-LymphocyteTNF geneTrainingVaccinesValidationadaptive immune responseadaptive immunitybeta-Glucanscandidemiacathelicidin antimicrobial peptidechemokinechronic infectioncytokinediagnostic toolepigenomeepigenomic profilingepigenomicshistone methylationimmune functionin vivoinfection rateinhibitorinnate immune functioninnovationinsightmachine learning modelmethylation patternmortalitymultiple omicsmutantnetwork modelsnovelpathogenperipheral bloodpharmacologicpredictive modelingpredictive signatureprogramspromoterprophylacticresistant strainresponsestatistical learningsurvival outcometargeted treatmenttherapeutic developmenttherapeutic targettranscription factortranscriptometranscriptome sequencingtranscriptomicswhole genome
项目摘要
PROJECT SUMMARY
Hematologic disseminated candidiasis (HDC) is the most common invasive fungal species in hospital settings
worldwide. The mortality rate is high (40%) for these infections despite treatment with antifungal therapies.
Similarly, methicillin-resistant strains of Staphylococcus aureus (MRSA) can cause invasive and life-threatening
infections despite treatment with standard anti-infective therapies. Thus, persistence reflects host-pathogen
interactions occurring uniquely in context of antibiotic therapy in vivo. However, host factors and mechanisms
involved in persistent MRSA and HDC remain unclear. This study will use systems-based, high-throughput
multi-omics platforms and novel statistical and computational approaches to provide a comprehensive
longitudinal assessment of host in vitro and in vivo innate and adaptive responses to HDC and MRSA infection
using patient peripheral blood, stimulus specific PAMPs and patient-derived HDC plasma PAMPs and isolates.
Innovative deliverables include: i) Constructing an in-depth immune profile of HDC and MRSA immune profiles;
ii) understand the stimulus-specificity of de novo enhancer formation in macrophages and how they affect
transcriptional landscapes and functions iii) generate a detailed molecular map of the cross-talk between the
innate and adaptive immune response during HDC and MRSA infection; iv) using the combination of
biostatistics and computational modeling to explain and predict cellular and molecular networks driving trained
immunity and persistent, resolving, and survival outcomes; and v) identification and validation of druggable
epigenomic regulators of reprogramming. Detailed insights into the interaction of HDC and MRSA with the host
immune system stand to generate fundamentally new mechanistic hypotheses and diagnostic tools to guide
development of therapeutic strategies.
项目总结
血液播散性念珠菌病(HDC)是医院最常见的侵袭性真菌种类
全世界。尽管接受了抗真菌治疗,但这些感染的死亡率很高(40%)。
同样,耐甲氧西林金黄色葡萄球菌(MRSA)可导致侵袭性和危及生命
尽管接受了标准的抗感染治疗,但仍受到感染。因此,持久性反映了宿主-病原体
在体内抗生素治疗的背景下发生的独特的相互作用。然而,宿主因素和机制
涉及持续性MRSA和HDC的情况仍不清楚。本研究将使用基于系统的高吞吐量
多组学平台和新颖的统计和计算方法提供全面的
宿主对HDC和MRSA感染的体内外先天和适应性反应的纵向评估
使用患者外周血、刺激特异性PAMP和患者来源的HDC血浆PAMP和分离物。
创新成果包括:i)构建HDC和MRSA免疫图谱的深度免疫图谱;
二)了解巨噬细胞新生增强子形成的刺激特异性及其如何影响
转录景观和功能III)生成详细的分子图谱
HDC和MRSA感染期间的先天和获得性免疫反应;iv)结合使用
用于解释和预测细胞和分子网络的生物统计学和计算模型
免疫和持久的、可分辨的和存活的结果;以及v)可用药物的鉴定和验证
重编程的表观基因组调控因子。对HDC和MRSA与宿主的互动的详细见解
免疫系统将从根本上产生新的机械性假说和诊断工具来指导
制定治疗策略。
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)
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{{ truncateString('ELAINE F REED', 18)}}的其他基金
Targeting YAP with statins to prevent antibody-mediated transplant rejection
用他汀类药物靶向 YAP 预防抗体介导的移植排斥
- 批准号:
10320048 - 财政年份:2020
- 资助金额:
$ 43.61万 - 项目类别:
The role of HLA and its coreceptors in endothelial cell activation and leukocyte recruitment in antibody-mediated transplant rejection
HLA 及其辅助受体在抗体介导的移植排斥中内皮细胞激活和白细胞募集中的作用
- 批准号:
10231220 - 财政年份:2018
- 资助金额:
$ 43.61万 - 项目类别:
The role of HLA and its coreceptors in endothelial cell activation and leukocyte recruitment in antibody-mediated transplant rejection
HLA 及其辅助受体在抗体介导的移植排斥中内皮细胞激活和白细胞募集中的作用
- 批准号:
10462514 - 财政年份:2018
- 资助金额:
$ 43.61万 - 项目类别:
Mapping Immune Responses to CMV in Renal Transplant Recipients - Transplant Supplement
绘制肾移植受者对 CMV 的免疫反应 - Transplant Supplement
- 批准号:
10225673 - 财政年份:2017
- 资助金额:
$ 43.61万 - 项目类别:
Mapping Immune Responses to CMV in Renal Transplant Recipients
绘制肾移植受者对 CMV 的免疫反应
- 批准号:
10000838 - 财政年份:2017
- 资助金额:
$ 43.61万 - 项目类别:
Ischemia-Reperfusion Injury in Human Liver Transplantation: Reciprocal Regulation of Innate/Adaptive Immune Responses
人肝移植中的缺血再灌注损伤:先天/适应性免疫反应的相互调节
- 批准号:
9975701 - 财政年份:2017
- 资助金额:
$ 43.61万 - 项目类别:
Mapping Immune Responses to CMV in Renal Transplant Recipients
绘制肾移植受者对 CMV 的免疫反应
- 批准号:
10225355 - 财政年份:2017
- 资助金额:
$ 43.61万 - 项目类别:
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