Contact Activation and Infection

接触激活和感染

基本信息

  • 批准号:
    10269038
  • 负责人:
  • 金额:
    $ 52.6万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-09-23 至 2025-08-31
  • 项目状态:
    未结题

项目摘要

Project Summary Our research project is designed to test our central hypothesis that the contact activation system contributes to pathologic mechanisms that lead to vascular dysfunction, thrombin generation, and inflammatory responses during systemic bacterial challenge by specific pathogens. Despite the availability of effective antibiotics, sepsis remains a prevalent clinical syndrome and significant cause of severe in-hospital morbidity and mortality, brought about by a sequence of rapidly advancing dynamic molecular and cellular events that occur upon exposure to and subsequent systemic infection by certain pathogens. Complicating the problem is the increasing prevalence of multiresistant bacterial pathogens. At present, after more than half a century of research, drug development, and countless clinical trials, there are still no FDA-approved marketed drugs specifically indicated for the treatment of sepsis. Sepsis can lead to multiple organ system failure, including failure of vasoregulation, poor tissue perfusion, edema, and systemic hypotension, which are hallmarks of severe sepsis. By triggering cardiopulmonary and vascular collapse, it is often lethal even with available supportive and antibiotic treatments. Sepsis may be accompanied by disseminated intravascular coagulation (DIC), which can lead to both thrombosis and bleeding due to the consumptive coagulopathy. We focus on the contact activation system, because 1) there appears to be a causal relationship between activation of coagulation factor XII and the poor prognosis of some forms of sepsis, and 2) targeting the contact activation system as a therapeutic approach is unlikely to have detrimental consequences for the host such as bleeding. We will study the role of the molecular steps in the contact activation system in the development and outcome of experimental bacterial infection, in vivo. We will define the roles of FXII (Aim 1) and its procoagulant substrate FXI (Aim 2), and translate our mechanistic in vitro studies to characterize the pathological role of contact activation in two distinct baboon models of bacterial infection. The potential translational relevance of our project will be the identification of safe and druggable molecular targets and mechanisms within the contact activation system. Our research may ultimately provide rationale for the development of selective contact activation inhibitors that could safely benefit patients that have or are at risk of infections by pathogens that can cause contact system activation.
项目总结

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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FLOREA LUPU其他文献

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{{ truncateString('FLOREA LUPU', 18)}}的其他基金

Complement C5 inhibition as sepsis therapy
补体 C5 抑制作为脓毒症治疗
  • 批准号:
    10569623
  • 财政年份:
    2022
  • 资助金额:
    $ 52.6万
  • 项目类别:
Complement C5 inhibition as sepsis therapy
补体 C5 抑制作为脓毒症治疗
  • 批准号:
    10420351
  • 财政年份:
    2022
  • 资助金额:
    $ 52.6万
  • 项目类别:
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
  • 财政年份:
    2021
  • 资助金额:
    $ 52.6万
  • 项目类别:
Contact Activation and Infection
接触激活和感染
  • 批准号:
    10676088
  • 财政年份:
    2020
  • 资助金额:
    $ 52.6万
  • 项目类别:
Contact Activation and Infection
接触激活和感染
  • 批准号:
    10458712
  • 财政年份:
    2020
  • 资助金额:
    $ 52.6万
  • 项目类别:
FXI and Sepsis
FXI 和败血症
  • 批准号:
    9127988
  • 财政年份:
    2015
  • 资助金额:
    $ 52.6万
  • 项目类别:
MICROSCOPY
显微镜
  • 批准号:
    8364980
  • 财政年份:
    2011
  • 资助金额:
    $ 52.6万
  • 项目类别:
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:
    $ 52.6万
  • 项目类别:
Intravital Multiphoton Microscope
活体多光子显微镜
  • 批准号:
    7794743
  • 财政年份:
    2010
  • 资助金额:
    $ 52.6万
  • 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:
    $ 52.6万
  • 项目类别:

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