Role of IL-22/IL-22RA2 during pneumococcal pneumonia

此申请表是K01导师职业发展奖的申请表，该奖项旨在促进 生物医学研究。特雷韦霍-努涅斯博士将研究IL-22/IL-22RA2在肺炎球菌病中的作用 肺炎。在美国，肺炎球菌肺炎(由肺炎链球菌引起的肺部感染)占 发病率和死亡率占很大比例。最易受伤害的人群是年龄小于 2岁和65岁以上的个人。 这位候选人有数据表明，肝脏中的IL-22信号对控制肺炎球菌很重要 肺炎和细胞因子IL-22的治疗改善了细菌负荷。总体假设是 通过治疗性应用IL-22或不使用诱饵来增强IL-22信号 受体IL-22RA2通过维持STAT3水平促进细菌清除和宿主存活 肺炎球菌肺炎时肺上皮和肝脏的激活。为了检验这一假设， 候选人建议1)确定内源性诱骗受体IL-22RA2的肺细胞来源 未受感染的宿主和肺炎球菌肺炎期间。2)验证IL-22Ra1增强的预测 靶组织中的信号控制肺炎期间的细菌负荷。3)检验预测 IL-22信号增强导致肺组织STAT-3持续激活而不依赖gp130/SOCS3 上皮细胞和肝脏。 特雷韦霍-努内斯博士是加州大学儿科学博士后、医学讲师。 匹兹堡医学院。她提出了一个职业发展计划，重点是：一对一 每周与她的导师Jay Kolls博士会面，学习使用转基因和 条件基因敲除小鼠，参加学术课程以加强她的免疫学基础， 统计、实验设计和赠款撰写；参加负责任的研究研讨会， 每6个月与她的审查咨询委员会举行一次会议，参加会议和出版 作为第一作者的手稿。特雷韦霍-努涅斯博士的长期目标是成为一名独立的医生- 在肺炎链球菌肺部感染的免疫学和宿主反应方面具有特殊专业知识的科学家。 候选人还计划收集足够的信息和数据分析，以便在年底申请R01资金 这个奖项的获得者。

This application is for a K01 Mentored Career Development Award to Promote Faculty Diversity in Biomedical Research. Dr. Trevejo-Nunez will investigate the role of IL-22/ IL-22RA2 during pneumococcal pneumonia. In United States, pneumococcal pneumonia (lung infection caused by S. pneumoniae) accounts for significant percentage of morbidity and mortality. The most vulnerable population are children younger than 2 years old and individuals older than 65. The candidate has data that shows IL-22 signaling in the liver is important for control of pneumococcal pneumonia and that treatment with the cytokine IL-22 improves bacterial burden. The overall hypothesis is that enhancement of IL-22 signaling, through therapeutic administration of IL-22 or absence of decoy recptor IL-22RA2, favors bacterial clearance and host survival by sustaining the levels of STAT3 activation in lung epithelium and liver during in pneumococcal pneumonia. To test this hypothesis, the candidate proposes 1) Define the lung cellular sources of endogenous decoy receptor IL-22RA2 in the uninfected hosts and during pneumococcal pneumonia. 2) Test the prediction that enhanced IL-22RA1 signaling in target tissues controls bacterial burden during pneumococcal pneumonia. 3) Test the prediction that enhanced IL-22 signaling results in sustained STAT-3 activation imdependent of gp130/SOCS3 in lung epithelium and liver. Dr. Trevejo-Nunez is Postdoctoral Associate of Pediatrics/ Instructor of Medicine at the University of Pittsburgh School of Medicine. She proposes a career development plan that focuses on: one- to- one meetings with her mentor Dr. Jay Kolls every week, learning mouse model of infection using transgenic and conditional knockout mice, attending academic coursework to strengthen her foundation in immunology, statistics, experimental design and grant writing; participating in responsible conduct of research workshops, meeting with her review advisory committee every 6 months, attending conferences and publishing manuscripts as first author. Dr. Trevejo-Nunez's long term goal is to become an independent physician- scientist with particular expertise in the immunology and host response against S. pneumoniae lung infection. The candidate also plans to gather enough information and analysis of data to apply for R01 funding at the end of this award.