Patient-Oriented Research on Pseudomonas aeruginosa

这份K24续订申请为豪泽博士提供了33%的薪资努力，并补充了机构支持 他一直指导医学和医学/博士研究员和初级教员，并扩大了他的病人- 以研究计划为导向。豪泽实验室的一个重点是确定铜绿假单胞菌的生物标志物 这定义了特别具有攻击性的菌株。过去的工作已经成功地识别出了几个基因 在小鼠模型中与更严重的感染有关。拟议研究的目标是扩大 这些针对人类患者群体的研究。在第一个项目中，重点将放在急性呼吸道疾病上 感染。引起特别严重呼吸机相关性肺炎的菌株与铜绿假单胞菌相关基因 将确定重症监护病房患者中的肺炎。为了开始将基因解析成功能类别， 那些让铜绿假单胞菌抵抗中性粒细胞杀戮的基因也将被识别出来。在第二个项目中， 重点将放在慢性呼吸道感染上。将使用系统生物学方法来鉴定P. 能够在囊性纤维化患者的呼吸道中持续存在的铜绿假单胞菌。一种小鼠模型 然后将使用慢性呼吸道感染来确定这些菌株的某些方面是否在 坚持不懈。这些项目将强大的基因组、遗传和微生物学技术与人类 样本和相应的临床数据，以产生以患者为导向的尖端研究。因此，它们是理想的 为初级临床医生研究人员提供培训工具，并有可能导致患者护理的改善。 学员将参加一项严格而广泛的指导计划，该计划利用了许多可用的资源 在西北大学，他们最大限度地发展成为独立的、以患者为导向的研究人员。在……里面 总结，这项K24奖励将提供工资支持和研究资金，使豪泽博士能够花费 他的大部分工作是指导临床研究员和初级教员进行以患者为导向的研究，并 扩大他的以病人为中心的研究计划。

This K24 renewal application provides 33% salary effort for Dr. Hauser and supplements institutional support for his continued mentoring of MD and MD/PhD fellows and junior faculty and for expansion of his patient- oriented research program. A focus of the Hauser Lab is to identify biomarkers of Pseudomonas aeruginosa that define particularly aggressive strains. Past work has successfully identified several genes that are associated with more severe infections in mouse models. The goal of the proposed research is to expand these studies into populations of human patients. In the first project, the focus will be on acute respiratory infections. P. aeruginosa genes associated with strains that cause especially severe ventilator-associated pneumonia in intensive care unit patients will be identified. To begin to parse genes into functional categories, those genes that allow P. aeruginosa to resist killing by neutrophils will also be identified. In the second project, the focus will be on chronic respiratory infections. A systems biology approach will be used to identify P. aeruginosa strains capable of persisting in the airways of individuals with cystic fibrosis. A mouse model of chronic airway infection will then be used to determine whether aspects of these strains play a causal role in persistence. These projects combine powerful genomic, genetic, and microbiological techniques with human specimens and corresponding clinical data to yield cutting-edge patient-oriented research. They are thus ideal training vehicles for junior clinician investigators and have the potential to lead to improvements in patient care. Mentees will participate in a rigorous and broad mentoring program that utilizes the many resources available at Northwestern University to maximize their development into independent patient-oriented researchers. In summary, this K24 award will provide salary support and research funds to allow Dr. Hauser to spend a substantial portion of his effort mentoring clinical fellows and junior faculty in patient-oriented research and to expand his patient-oriented research program.