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

IL-22/IL-22RA2 在肺炎球菌肺炎中的作用

基本信息

批准号：
10198015
负责人：
Giraldina Trevejo-Nunez
金额：
$ 16.73万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-15 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10198015
关键词：
2 year old Advisory Committees Affinity Alveolar Macrophages Award Binding Biomedical Research Cause of Death Cells Cessation of life Child Chronic Chronic Disease Complement Data Data Analyses Development Plans Diabetes Mellitus Disease Educational workshop Epithelial Epithelial Cells Experimental Designs Faculty Foundations Funding Future Goals Grant HIV Heart Diseases Hepatic Hepatocyte Hospitalization IL10RB gene IL6ST gene Immune response Immunity Immunology Individual Infection Infection Control K-Series Research Career Programs Knockout Mice Knowledge Learning Liver Lung Lung diseases Lung infections Manuscripts Medicine Mentors Modeling Molecular Morbidity - disease rate Mus Organ Pathway interactions Patients Pediatrics Phagocytosis Phosphorylation Physicians Play Pneumococcal Infections Pneumococcal Pneumonia Pneumonia Population Process Proteins Publishing Receptor Activation Recombinants Regulation Role STAT3 gene Scientist Signal Transduction Site Smoker Source Streptococcus pneumoniae Testing Therapeutic Tissues Transcriptional Regulation Transgenic Organisms United States Universities Vulnerable Populations Writing career development community acquired pneumonia conditional knockout cytokine gain of function high risk improved insight instructor interleukin-22 loss of function medical schools meetings mortality mouse model novel overexpression pneumonia treatment prevent receptor response responsible research conduct statistics symposium targeted treatment

项目摘要

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.

此申请适用于 K01 指导职业发展奖，以促进教师多样性生物医学研究。 Trevejo-Nunez 博士将研究 IL-22/ IL-22RA2 在肺炎球菌治疗过程中的作用肺炎。在美国，肺炎球菌肺炎（由肺炎链球菌引起的肺部感染）的情况发病率和死亡率的显着百分比。最脆弱的人群是 2 岁以下的儿童 2岁及65岁以上人士。该候选人的数据显示肝脏中的 IL-22 信号传导对于控制肺炎球菌非常重要肺炎，细胞因子 IL-22 治疗可改善细菌负荷。总体假设是通过治疗性给予 IL-22 或不使用诱饵来增强 IL-22 信号传导受体 IL-22RA2，通过维持 STAT3 水平有利于细菌清除和宿主存活肺炎球菌肺炎期间肺上皮和肝脏的激活。为了检验这个假设，候选人建议 1) 定义内源性诱饵受体 IL-22RA2 的肺细胞来源未感染的宿主和肺炎球菌肺炎期间。 2) 测试增强IL-22RA1的预测靶组织中的信号传导控制肺炎球菌肺炎期间的细菌负荷。 3）测试预测增强的 IL-22 信号传导导致肺中不依赖于 gp130/SOCS3 的持续 STAT-3 激活上皮和肝脏。 Trevejo-Nunez 博士是马里兰大学儿科博士后/医学讲师匹兹堡医学院。她提出了一个职业发展计划，重点关注：一对一每周与她的导师 Jay Kolls 博士会面，学习使用转基因和病毒感染的小鼠模型条件性基因敲除小鼠，参加学术课程以加强她的免疫学基础，统计、实验设计和资助写作；参与负责任地举办研究研讨会，每 6 个月与她的审查咨询委员会会面一次，参加会议并发表论文作为第一作者的手稿。 Trevejo-Nunez 博士的长期目标是成为一名独立医生—— 科学家，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的专业知识。候选人还计划收集足够的信息和数据分析，以在最后申请 R01 资金的这个奖项。