权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Cellular regulation of the IL-22 receptor and its importance in lung immunity.

IL-22 受体的细胞调节及其在肺免疫中的重要性。

基本信息

批准号：
8805079
负责人：
NATHANIEL M WEATHINGTON
金额：
$ 12.68万
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：
2014
资助国家：
美国
起止时间：
2014-12-01 至 2019-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8805079
关键词：
Address Animal Model Animals Award Bacteria Bacterial Infections Bacterial Pneumonia Biological Biology Cell membrane Cells Cessation of life Clinical Containment Critical Care Cytokine Receptors Data Disease Doctor of Philosophy Effector Cell Environment Enzymes Epithelial Epithelial Cells Epithelium Fellowship Functional disorder Gases Glycogen Synthase Kinase 3 Health Host Defense Human Hypersensitivity Immune Immune response Immunity In Vitro Infection Inflammatory Influenza Interleukins Irritants K-Series Research Career Programs Klebsiella pneumonia bacterium Laboratories Leukocytes Ligation Lung Lung Inflammation Lysosomes Mediating Medicine Mentors Molecular Mus Normal tissue morphology Organ Patients Phosphorylation Phosphotransferases Pneumonia Post-Translational Protein Processing Process Production Protein Chemistry Proteins Publications Pulmonary Inflammation Recovery Regulation Research Rest Role STAT3 gene Sampling Sepsis Signal Transduction Signaling Protein Specimen Surface System Techniques Testing Training Translational Research Translations Ubiquitin Ubiquitination Universities Work antimicrobial peptide base career development cell growth regulation cytokine immune activation in vivo interleukin-22 killings mouse model multicatalytic endopeptidase complex novel pathogen personalized medicine prevent professor protein degradation public health relevance receptor receptor binding response ubiquitin-protein ligase

项目摘要

DESCRIPTION (provided by applicant): This application, Cellular regulation of the IL-22 receptor and its importance in lung immunity, is submitted by me, Dr. Nathaniel Weathington, MD PhD in the University of Pittsburgh Department of Medicine, Division of Pulmonary Allergy, and Critical Care Medicine for a mentored Career Development Award (K08). I have a strong background and commitment to research in pulmonary inflammation biology with aspirations to ultimately direct a center on lung inflammation biology. I propose a research-intensive period of career development with hands-on and didactic training integrated into the activities planned. To complete my primary research Aims, I will gain and extend expertise in protein chemistry, cell biologic, and animal model techniques. I present preliminary data on modulation of the interleukin (IL)-22 signaling axis, which is essential and protective for Type 17 immune responses. Molecular regulation of IL-22 receptor (IL-22R) protein levels is unknown, and I show that IL-22R is degraded by the ubiquitin (Ub) proteasome with identification of a molecular motif for IL-22R ubiquitination. I also observe that the uncharacterized Ub E3 ligase subunit FBXW22 shuttles the IL-22R protein for degradation in lung epithelial cells. Further, the multi-functional kinase glycogen synthase kinase 3 phosphorylates and stabilizes IL-22R in cells. Based on this, I propose to more specifically characterize IL-22R regulation, study abundance of involved proteins in human specimens for disease correlation, and test the hypothesis that stabilization of IL-22R in vivo can protect from pneumonia. My work will proceed under close advisement from my primary mentor and research advisors. I also propose select coursework for enrichment on translational science and personalized medicine. I have an environment of enduring support at the University of Pittsburgh from my advisors, mentor, division, and department, and will be promoted to Assistant Professor of Medicine on completion of my fellowship in summer 2014. With support from the K08 mentored Career Development Award, this project will yield publications and presentations, and I will develop my research to an independent project with a transition to independence and application for an R01 project award in the next five years.