Trauma Reprograms Cells

我们的领导团队的资深调查人员提出3个项目，以解决目前最可预防的 损伤后死亡率的来源：创伤诱导的凝血功能障碍（TIC）和发病率： 幸存者我们被鼓励成为文化的一部分，帮助减少多器官 失败，财政部，在十年内。有经验的管理核心将像以前一样执行此程序。 通过结合以前每个项目的突出发现，护理点研究的突破， 在SIMP核心和HS核心临床数据的指导下，我们确定了最重要的问题和可测试的 假设项目1，2和3锚本身的凝血功能，蛋白质组学和代谢组学 匹配的患者样本，然后继续推导实验方法， 项目1由摩尔博士、Silliman博士、Sauaia博士和Banerjee博士组成的领导小组研究了纤溶酶 导致急性死亡的表型。他们假设失血性休克容易导致 纤溶酶原/纤溶酶的调节导致纤维蛋白溶解过度，但组织损伤导致纤维蛋白溶解关闭。的 在休克的动物模型中和在患者的高内容数据中检验假设。 由Silliman博士、Banerjee博士、汉森博士、摩尔博士、Sauaia博士和 Dziecatowskowa设计这些目的是研究创伤后血浆中发现的纤溶酶的新型调节剂。 他们专注于含有（Kringles，钙调蛋白或纤连蛋白）结构域的蛋白质，这些结构域在血液后变得丰富 储存，或在出血性休克与组织损伤的条件下，似乎是人类 纤溶酶。 项目3领导团队由D 'Alessandro、Peltz、Banerjee、Silliman、摩尔和Sauaia博士组成 设计这些目标是为了具体了解血浆酸度的阴离子贡献者（Aim 1）。他们假设 创伤和失血性休克引起不同的代谢变化，导致全身病理学， 可以通过代谢组学分析来鉴定。他们评估了琥珀酸和谷氨酰胺升高的作用， 代谢（Aim 2）和潜在的微生物产生的代谢产物，用于下一代复苏治疗。 这些目标将导致在未来十年内切实降低急性死亡率和幸存者发病率， 由验证科学机制的HS核心和SIMP核心和管理支持 核心是保证能力。

Our leadership team of veteran investigators propose 3 projects to address the currently most preventable sources of postinjury mortality: trauma induced coagulopathy (TIC) and morbidity: delayed lung dysfunction in survivors. We are encouraged to be part of the culture that helped dwindle the incidence of Multiple Organ Failure, MOF, in a decade. An experienced Administration Core will execute this program as before. By combining salient discoveries in each previous project, breakthroughs in point of care research, enabled by SIMP Core and guided by clinical data in the HS Core, we identify the most important questions and testable hypotheses. Projects 1, 2 and 3 anchor themselves on coagulative functionality, proteomics and metabolomics on matched patient samples and then continue to derive experimental approaches Project 1 The leadership team consisting of Drs. Moore, Silliman, Sauaia and Banerjee examine fibrinolytic phenotypes that contribute to acute mortality. They hypothesize that hemorrhagic shock predisposes to hyperfibrinolysis, but tissue injury causes fibrinolysis shut-down, due to regulation of plasminogen/plasmin. The hypotheses are tested in animal models of shock and with high content data on patients. Project 2 The leadership team consisting of Drs. Silliman, Banerjee, Hansen, Moore, Sauaia and Dziecatowskowa designed these aims to investigate novel regulators of plasmin found in post traumatic plasma. They focus on proteins containing (kringles, calponin or fibronectin) domains that become abundant after blood storage, or in conditions of hemorrhagic shock versus tissue injury, and appear to be novel regulators of human plasmin. Project 3 The leadership team consisting of Drs. D'Alessandro, Peltz, Banerjee, Silliman, Moore, and Sauaia designed these aims to specifically understand anionic contributors to plasma acidity (Aim1). They hypothesize that trauma and hemorrhagic shock instigate different metabolic changes resulting in systemic pathology, which can be identified by metabolomics analysis. They assess the role of elevated succinate and glutamine metabolism (Aim2) and potential microbially generated metabolites, for Next-Gen resuscitation therapy. These aims will lead to pragmatically attenuating acute mortality and survivor morbidity within the next decade, are supported by an active HS core that verifies scientific mechanisms and a SIMP Core and Administration Core that ensure capability.