Human Immunomics & Trained Immunity in Persistent Candidemia

人类免疫组学

基本信息

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

项目成果

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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:
Core-004
核心004
  • 批准号:
    10167305
  • 财政年份:
    2020
  • 资助金额:
    $ 43.61万
  • 项目类别:
Core-002
核心002
  • 批准号:
    10167302
  • 财政年份:
    2020
  • 资助金额:
    $ 43.61万
  • 项目类别:
Core-003
核心003
  • 批准号:
    10167304
  • 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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