R35 Undergraduate Research Supplement

伤害和创伤是常见的疾病，包括相当大的疾病负担， 医疗保健费用的主要组成部分。内皮细胞（EC）是血液和身体之间的纽带， 并且创伤中内皮功能的破坏导致内皮病综合征，其特征在于受损的 微血管血流、屏障完整性和凝血。我们缺乏对EC如何翻译 创伤信号转化为血管舒张、屏障和凝血功能的变化代表了显著的空白， 也是临床干预的机会。我实验室的中心主题是了解 创伤和炎症，这样我们就可以改善结果。这项研究计划将提供一种分子 组蛋白对血管内皮细胞的直接和持续作用的机制模型 这解释了创伤患者中出现的振荡凝血反应。该项目还将测试新的 保护和/或挽救创伤后内皮功能障碍的策略。预计拟议的研究将 显著推进改善急性胰腺炎诊断和管理所需的连续研究， 创伤性内皮病此外，它有可能从根本上改变我们对内皮生物学的看法。这 这项研究将对了解内皮细胞在健康中的作用产生持久和持续的影响。 和疾病

Injury and trauma are common conditions that encompass a considerable burden of illness and account for a major component of health care costs. Endothelial cells (ECs) are the nexus between the blood and the body, and disruption of endothelial function in trauma leads to a syndrome of endothelipathy characterized by impaired microvascular blood flow, barrier integrity and coagulation. Our lack of understanding of how ECs translate the signals of trauma into changes in vasodilatory, barrier and coagulation functions represents a significant void— but also an opportunity for clinical intervention. The central theme of my lab is to understand endotheliopathy in trauma and inflammation, so that we can improve outcomes. This research program will deliver a molecular model of the mechanisms by which histones cause both immediate and sustained effects on vascular endothelium that explain oscillating clotting responses seen in trauma patients. This project will also test novel strategies to protect and/or rescue endothelial dysfunction after trauma. The proposed research is expected to significantly advance the continuum of research needed to improve diagnosis and management of acute endotheliopathy in trauma. Moreover, it has the potential to radically change our view of endothelial biology. This research will provide an enduring and sustained impact on understanding the role of the endothelium in health and disease.