Patient-Oriented Research on Pseudomonas aeruginosa

此K24续约申请为豪瑟博士提供33%的工资努力，并补充机构支持 他继续指导MD和MD/PhD研究员和初级教师，并扩大他的病人- 导向研究计划。豪瑟实验室的一个重点是鉴定铜绿假单胞菌的生物标志物 定义了特别具有攻击性的菌株。过去的工作已经成功地确定了几个基因， 与小鼠模型中更严重的感染有关。这项研究的目的是扩大 这些研究是针对人类患者群体的。在第一个项目中，重点将是急性呼吸道疾病， 感染.铜绿假单胞菌基因与引起特别严重的呼吸机相关性 重症监护室患者的肺炎将被识别。为了开始将基因解析为功能类别， 还将鉴定那些允许铜绿假单胞菌抵抗嗜中性粒细胞杀伤的基因。在第二个项目中， 重点是慢性呼吸道感染。系统生物学方法将被用来识别P。 铜绿假单胞菌菌株能够在囊性纤维化个体的气道中持续存在。的小鼠模型 慢性呼吸道感染将被用来确定这些菌株的某些方面是否在 持久性。这些项目结合了联合收割机强大的基因组，遗传和微生物技术与人类 标本和相应的临床数据，以产生尖端的以病人为导向的研究。因此，它们是理想的 初级临床研究人员的培训工具，并有可能导致改善病人护理。 学员将参加一个严格而广泛的指导计划，利用许多可用的资源 在西北大学，最大限度地提高他们的发展成为独立的以病人为导向的研究人员。在 总之，这个K24奖将提供工资支持和研究资金，让豪瑟博士花一个 他的大部分工作是指导临床研究员和初级教师进行以患者为导向的研究， 扩大他的病人导向研究项目

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.