Trauma Reprograms Cells

创伤重新编程细胞

基本信息

批准号：
9209196
负责人：
ANIRBAN BANERJEE
金额：
$ 155.12万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-04-01 至 2019-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9209196
关键词：
Accountability Acidity Acute Address Adult Affect Affinity Animal Experiments Animal Model Animal Organ Animals Attention Attenuated Awareness Biochemistry Bioinformatics Biological Assay Biological Models Biometry Biophysics Blood Blood Coagulation Disorders Cause of Death Cells Chronic Clinical Data Coagulation Process Colorado Critical Care Custom Data Data Collection Diagnostic Discipline Ensure Epidemiology Fibrinolysis Fibronectins Functional disorder Glutamine Goals Head Hemoglobin Hemorrhagic Shock Human Hypoxia Image Incidence Individual Injury Intention Kringles Lead Leadership Light Link Liquid substance Lung Lung Inflammation Mediator of activation protein Metabolic Metabolism Mission Mitochondria Modeling Morbidity - disease rate Multiple Organ Failure Operative Surgical Procedures Outcome Paramedical Personnel Pathology Patients Phenotype Philosophy Plasma Plasmin Plasminogen Population Proteins Proteome Proteomics Regulation Research Research Personnel Resuscitation Role Sampling Secure Shock Source Succinates Survivors Technology Testing Tissues Translational Research Trauma Trauma Research Universities Veterans Whole Blood base bench to bedside blood product calponin demographics design enolase experience frontier gamma Actin improved insight interest member metabolomics microbial mortality novel point of care programs protein complex viscoelasticity

项目摘要

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.

我们的资深调查人员领导团队提出了3个项目，以解决当前最可预防的项目损害后死亡率的来源：创伤引起的凝血病（TIC）和发病率：延迟的肺功能障碍幸存者。鼓励我们成为有助于减轻多器官发病率的文化的一部分失败，MOF，十年。经验丰富的管理核心将像以前一样执行此程序。通过在每个先前项目中结合显着的发现，在护理研究中的突破，由 SIMP核心并在HS核心中的临床数据的指导下，我们确定了最重要的问题和可测试的问题假设。项目1、2和3基于凝结功能，蛋白质组学和代谢组学在匹配的患者样品中，然后继续得出实验方法项目1由DRS组成的领导团队。 Moore，Silliman，Sauaia和Banerjee检查纤维蛋白水解导致急性死亡率的表型。他们假设出血性休克易于高纤维蛋白溶解，但由于纤溶酶原/纤溶酶的调节，组织损伤会导致纤维蛋白溶解关闭。这在休克动物模型中测试了假设，并具有有关患者的高含量数据。项目2由DRS组成的领导团队。 Silliman，Banerjee，Hansen，Moore，Sauaia和 Dziecatowskowa设计了这些目的是研究创伤后血浆中发现的新型纤溶酶调节剂。他们专注于含有蛋白质（kringles，calponin或纤连蛋白）结构域，这些结构域在血液后变得丰富存储，或在出血性休克与组织损伤的条件下，似乎是人类的新调节剂纤溶酶。项目3由DRS组成的领导团队。 D'Alessandro，Peltz，Banerjee，Silliman，Moore和Sauaia 设计这些目的是专门了解血浆酸度的阴离子贡献者（AIM1）。他们假设这种创伤和出血性休克促使不同的代谢变化导致全身病理，这可以通过代谢组学分析来识别。他们评估琥珀酸酯和谷氨酰胺升高的作用代谢（AIM2）和潜在的微生物产生的代谢产物，用于下一代复苏疗法。这些目标将导致务实地衰减急性死亡率和未来十年的幸存者发病率，由活跃的HS核心支持，该核心验证科学机制和SIMP核心和管理确保能力的核心。