Multiscale Analysis of Trauma

创伤的多尺度分析

基本信息

  • 批准号:
    9032214
  • 负责人:
  • 金额:
    $ 75.63万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2016
  • 资助国家:
    美国
  • 起止时间:
    2016-05-01 至 2021-01-31
  • 项目状态:
    已结题

项目摘要

 DESCRIPTION (provided by applicant): In response to PAR-15-085, the University of Pennsylvania and Princeton University have assembled an interdisciplinary team of bioengineers, computational scientists, trauma surgeons, and hematologists to develop a multiscale model of trauma. Better elucidation and quantitative measurement of blood reactions, platelet signaling, neutrophil signaling, and endothelial signaling pathways under hemodynamic conditions are directed at clinical needs in: (i) stratifying trauma induced coagulopathy (TIC) risks, (ii) improving the safety and efficacy of transfusion therapy, and (iii) identifying moleculr mechanisms that can be targeted pharmacologically or serve as improved biomarkers. Six specific aims are proposed: Aims 1 and 2 focus on the development of mechanistic and data-driven computer models of biochemical and cellular function relating to: protease cascades of coagulation, fibrinolysis, and complement assembly, as well as platelet, neutrophil and endothelial function. Aim 3 then develops a multiscale model of blood clotting and hemostatic function in a damaged blood vessel. The individual sub-models at the single cell level are combined into the unit vessel bleeding model which is related closely to laboratory experiments that test the functional performance of mouse and human patient blood under the extreme conditions of trauma. Aim 3 also involves microfluidic bleeding assays of human blood under diverse pathological conditions that explore bleeding scenarios involving combinatorial alterations of biochemistry and biology relevant to trauma. Aim 4 will implement "coarse projective integration" (CPI) to make prediction of the evolving systemic circulation and its interaction with a traumatized tissue where bleeding is quantified at the single cell to single vessel to tissue scale. These simulations are designed to validate an in silico trauma patient in order to stratify the risk of TIC. In Aim 5, the intensive use of fresh blood samples from trauma patients and annotated records from trauma patients will be part of the validation of the multiscale CPI algorithm. Key preliminary data demonstrates detection and quantification of platelet hypofunction in trauma patients. Aim 6 will utilize a novel in vivo mouse injury model to study bleeding and hemostasis in a calibrated model of trauma severity. This in vivo data will also be used to enhance the predictive capability of the multiscale model and to potentially identify biomarkers for stratifying TIC risks in humans. Also the mouse work emphasizes the use of novel fluorescent sensors developed specifically for this research. Overall, these aims represent the full integration of platelet, neutrophil, and endothelial signaling models with realistic and hierarchical hemodynamic/mass transport simulations that regulate bleeding and blood function at the various scales relevant to trauma.


项目成果

期刊论文数量(0)
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{{ truncateString('SCOTT L DIAMOND', 18)}}的其他基金

Neonatal and Pediatric Platelet Function and Pharmacology
新生儿和儿童血小板功能和药理学
  • 批准号:
    9759659
  • 财政年份:
    2018
  • 资助金额:
    $ 75.63万
  • 项目类别:
Multiscale Analysis of Trauma
创伤的多尺度分析
  • 批准号:
    9264028
  • 财政年份:
    2016
  • 资助金额:
    $ 75.63万
  • 项目类别:
Neonatal and Pediatric Platelet Function and Pharmacology
新生儿和儿童血小板功能和药理学
  • 批准号:
    9292339
  • 财政年份:
    2015
  • 资助金额:
    $ 75.63万
  • 项目类别:
Neonatal and Pediatric Platelet Function and Pharmacology
新生儿和儿童血小板功能和药理学
  • 批准号:
    8908392
  • 财政年份:
    2015
  • 资助金额:
    $ 75.63万
  • 项目类别:
Neonatal and Pediatric Platelet Function and Pharmacology
新生儿和儿童血小板功能和药理学
  • 批准号:
    9103240
  • 财政年份:
    2015
  • 资助金额:
    $ 75.63万
  • 项目类别:
Blood Systems Biology
血液系统生物学
  • 批准号:
    8134883
  • 财政年份:
    2010
  • 资助金额:
    $ 75.63万
  • 项目类别:
Blood Systems Biology
血液系统生物学
  • 批准号:
    7934185
  • 财政年份:
    2010
  • 资助金额:
    $ 75.63万
  • 项目类别:
Core C: Genomics and High Throughput Screening Core
核心 C:基因组学和高通量筛选核心
  • 批准号:
    8066104
  • 财政年份:
    2010
  • 资助金额:
    $ 75.63万
  • 项目类别:
Blood Systems Biology
血液系统生物学
  • 批准号:
    8927743
  • 财政年份:
    2010
  • 资助金额:
    $ 75.63万
  • 项目类别:
Blood Systems Biology
血液系统生物学
  • 批准号:
    8293284
  • 财政年份:
    2010
  • 资助金额:
    $ 75.63万
  • 项目类别:

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组合细胞因子包被的巨噬细胞用于急性肺损伤的靶向免疫调节
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