Patient-Oriented Research in Acute Lung Injury and Host Defense in the ICU

翻译后摘要：这个新的应用程序的总体目标是在以病人为导向的职业中期研究者奖 研究是为了使李博士建立一个研究和指导计划，在病人为导向的研究，在急性 肺损伤和宿主防御。ICU中的急性下呼吸道牵拉性感染（LRTI）仍然是一个巨大的 美国和全球的医疗保健负担。下呼吸道感染仍然是脓毒症的主要原因和急性肺损伤的危险因素 损伤细菌性下呼吸道感染也是急性肺损伤的常见并发症， 住院和医疗费用。李博士是一位医生科学家，专注于拓宽分子理解 通过探测宿主-病原体相互作用来阐明 使个体易受病原体诱导的损伤的宿主因素。该奖项将允许受保护的时间 专门的教学，培训和指导学员，包括初级教师，研究员，居民，和医疗 学生在转化研究的重点问题出现在危重病人。具体而言，指导将 支持对常见革兰氏阴性细菌引起急性下呼吸道感染的新研究 重症监护室的病原体主要假设是宿主-病原体相互作用的不同分子决定因素 在板凳上确定提供了独特的见解，与宿主防御机制的损害， ICU中的不良临床结局。提出了两个目标，利用 翻译研究的研究者。目的1将评估使患者易患组织炎的微生物因素 革兰氏阴性病原体铜绿假单胞菌（PA）引起的炎症和损伤 隔离在ICU。我们将测试在实验室鉴定的分子途径，以探索 病原体蛋白酶对患者结果的作用如下呼吸道中的微生物持久性， 无呼吸机天数、住院时间和死亡率。目标2将评估宿主体液免疫的损伤 在危重病期间，并检查与患者结局（包括多器官功能障碍）的关系， 死亡率、多重耐药ICU感染的获得和包裹革兰氏阴性菌的血清杀伤 病原体肺炎克雷伯氏菌。这个K24奖项将使李博士实现两个主要目标：（1）建立联系 基础生物学和医学之间的关系，通过探索ICU环境中的宿主-病原体相互作用， 了解危重病综合征，如ARDS;（2）进一步发展她的指导技能 她在分子重症监护领域开展了以患者为导向的研究，同时扩大了她的指导时间。 该奖项的成功执行将提高K24调查员的工作效率， 一群训练有素的临床研究人员，他们有能力将基础生物学转化为临床研究 再回来

Abstract: The overall goal of this new application for a Midcareer Investigator Award in Patient-Oriented Research is to enable Dr. Lee to build a research and mentoring program in patient-oriented research in acute lung injury and host defense. Acute lower respiratory traction infections (LRTI) in the ICU remains an enormous healthcare burden in the US and worldwide. LRTI remains a major cause of sepsis and risk factor for acute lung injury. Bacterial LRTI is also a frequent complication of acute lung injury that increases patient morbidity, length of stay and health-care costs. Dr. Lee is a physician scientist focused on broadening molecular understanding of critical illness syndromes such as acute lung injury by probing host-pathogen interplay to elucidate the biology of host factors that predispose individuals to pathogen-induced injury. This award will allow protected time for dedicated teaching, training, and mentoring of trainees that include junior faculty, fellows, residents, and medical students in translational research focusing on problems arising in critically ill patients. Specifically, mentoring will support novel investigations into acute lower respiratory tract infections from common Gram-negative bacterial pathogens in the ICU. The major hypothesis is that distinct molecular determinants of host-pathogen interplay identified at the bench provide unique insights into impairments of host defense mechanisms that associate with adverse clinical outcomes in the ICU. Two aims are proposed that leverage the unique capabilities of the investigator in translational research. Aim 1 will evaluate microbial factors that predispose patients to tissue inflammation and injury instigated by the Gram-negative pathogen Pseudomonas aeruginosa (PA) respiratory isolates in the ICU. We will test molecular pathways identified at the bench to explore the relationship between pathogen protease function to patient outcomes such as microbial persistence in the lower respiratory tract, ventilator-free days, length of stay and mortality. Aim 2 will evaluate impairments in host humoral immunity during critical illness and examine the relationship to patient outcomes including multiple organ dysfunction, mortality, acquisition of multi-drug resistant ICU infections, and serum killing of encapsulated Gram-negative pathogen Klebsiella pneumoniae. This K24 award will allow Dr. Lee to achieve two principal goals: (1) forge links between basic biology and medicine by probing host-pathogen interplay in the ICU setting and improve understanding of critical illness syndromes such as ARDS; and (2) to further develop her skills in mentoring trainees in patient-oriented research in molecular critical care while expanding her time devoted to mentoring. The successful execution of this award will enhance the productivity of both the K24 investigator and increase the pool of well-trained clinician investigators who are equipped to translate fundamental biology to the bedside and back.