Trauma Primes Cells

这份申请是我们资助的2000年创伤中心申请的延伸，也是我们获得2004-2005年过渡性资金的竞争性续签的重新提交。我们的全球假设是，人类核心(存储临床数据库和患者样本)与炎症信号机制研究之间的双向交流将有助于我们设计创伤原始细胞的治疗方法。自1993年首次资助以来，我们的MOF数据库大幅增长，对失血性休克(I)、输血(II)、组织损伤(IV)和抗炎复苏机制(V)固有的基本问题产生了新的见解。这些项目仍然高度依赖于彼此，并邀请人类核心进一步测试假设。Silliman的项目对淋巴和储存的血液中积累的类似脂肪代谢物进行了详细的分析，重点是肺内皮细胞。亚伯拉罕的项目专注于另一种普遍存在的细胞内蛋白HMGBP，它可能是由细胞因子或内毒素引起的炎症的倒数第二个效应物。奇怪的是，它的信号机制可能导致相同的内毒素受体途径。Banerjee的项目挑战了其他项目， 炎症因子依赖于大的信号复合体，这些复合体作为激活的受体被内化。因此，通过破坏内体-支架信号模块的组装，可以避免炎症表现。为了验证这些想法，人类核心负责提供样本，收集数据，并重新注释数据库，同时保持严格的法规遵从性。随着年轻的临床医生和生物统计学家回来质疑这个强大的数据库，我们重新评估了改变治疗的影响，并为未来周期的台架试验开发了新的假设。一个充满活力的细胞和成像核心将为每个项目提供常用的人类细胞，以及使用抗体进行先进的分子共定位和细胞学测量的设备和专业知识。这些努力得到了经验丰富的行政核心的支持，该核心寻求进一步加强我们三个机构的能力，以 发布创伤研究报告。

This application is an extension of our funded 2000 Trauma Center application and a resubmission of our competing renewal that was awarded bridge funding for 2004-2005. Our global hypothesis is that two-way exchanges between Human Core (housing clinical databases and patient samples) with mechanistic studies of inflammatory signaling will help us devise THERAPY FOR TRAUMA PRIMES CELLS. Since initial funding in 1993, our MOF databases have grown substantially to yield novel insights into fundamental problems inherent to hemorrhagic shock (I), transfusion (II), tissue injury (IV) and mechanisms of antiinflammatory resuscitation (V). The projects remain highly dependent on each other, and invite the Human Core to further test hypotheses. Project by Silliman undertakes a detailed analysis of analogous lipid metabolites accruing in lymph and stored blood, focusing on lung endothelium. Project by Abraham focuses on another type of ubiquitous intracellular protein HMGBP that may be the penultimate effector of inflammation, caused by either cytokines or LPS. Curiously, its signaling mechanism could lead to the same LPS receptor pathway. Project by Banerjee challenges other projects that signaling by inflammatory agents depends on large signaling complexes that form as activated receptors are internalized. Therefore, by disrupting assembly of the endosome-scaffolded signaling modules, inflammatory manifestations might be avoided. To validate these ideas, the Human Core is charged with supplying specimens, gather data, and re-annotate the database while remaining in strict regulatory compliance. With young clinicians and bio-statisticians returning to query this powerful database, we reassess the impact of changing therapy and develop new hypotheses for bench-testing in future cycles. A vigorous Cell & Imaging Core will provide each project with commonly used human cells, and equipment and expertise to perform advanced molecular colocalization and cytometry using antibodies. These efforts are supported by a seasoned Administrative Core that seeks to further the prowess of our three institutions to promulgate Trauma Research.