Trauma Reprograms Cells

我们由资深调查人员组成的领导团队提出了3个项目，以解决目前最可预防的 损伤后死亡的来源：创伤后凝血障碍(TIC)和发病率：延迟性肺功能障碍 幸存者。我们被鼓励成为帮助降低多器官发生率的文化的一部分 失败，财政部，在十年内。经验丰富的管理核心将一如既往地执行此程序。 通过结合以前每个项目中的突出发现，在关注点研究方面的突破，由 SIMP核心，并以HS核心中的临床数据为指导，我们确定了最重要的问题和可测试的 假设。项目1、2和3以凝血功能、蛋白质组学和代谢组学为基础 在匹配的患者样本上，然后继续推导出实验方法 项目1由摩尔博士、西里曼博士、索亚博士和班纳吉博士组成的领导小组检查纤溶 导致急性死亡的表型。他们假设失血性休克易患上 纤溶亢进，但组织损伤导致纤溶停止，这是由于纤溶酶原/纤溶酶的调节。这个 假说在休克的动物模型中得到了验证，并在患者身上获得了高含量的数据。 项目2领导小组由Silliman博士、Banerjee博士、Hansen博士、Moore博士、Sauaia博士和 Dziecatowskowa设计这些目的是为了研究在创伤后血浆中发现的纤溶酶的新调节剂。 他们专注于含有(kringles、calponin或fimenectin)结构域的蛋白质，这些结构域在血液中变得丰富 储存，或在失血性休克和组织损伤的条件下，似乎是人类的新调节器 纤溶酶。 项目3领导小组由D‘Alessandro博士、Peltz博士、Banerjee博士、Silliman博士、Moore博士和Sauaia博士组成 这些设计的目的是专门了解阴离子对血浆酸度的贡献(Aim1)。他们的假设是 创伤和失血性休克引起不同的代谢变化，导致全身病理， 可以通过代谢组学分析来鉴定。他们评估了升高的琥珀酸和谷氨酰胺的作用 代谢(AIM2)和潜在的微生物生成的代谢物，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， 由验证科学机制的主动HS核心和SIMP核心和管理支持 确保性能的核心。

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.