Adenovirus modulation of pulmonary inflammation

腺病毒调节肺部炎症

• 批准号: 7491750
• 负责人: Jason Brice Weinberg
• 金额: $ 13.21万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7491750
• 关键词: Acute; Address; Adenovirus E1A Proteins; Adenovirus Infections; Adenoviruses; Advisory Committees; Animals; Asthma; Bronchiolitis Obliterans; CCL2 gene; CCR5 gene; Cell Line; Cessation of life; Chemokine (C-C Motif) Receptor 5; Chronic Obstructive Airway Disease; Chronic Obstructive Asthma; Chronic lung disease; Clinical; Condition; Data; Development; Doctor of Philosophy; Environment; Genes; Goals; Human; Human Adenovirus Infections; Human Adenoviruses; Immune response; Immunocompromised Host; Immunology; In Vitro; Infection; Inflammatory; Inflammatory Response; Knock-out; Knockout Mice; Laboratories; Lead; Link; Long-Term Effects; Lung; Lung diseases; Mediating; Medicine; Mentors; Michigan; Modeling; Molecular Biology; Mus; Outcome; Outcomes Research; Pathogenesis; Pneumonia; Postdoctoral Fellow; Prevention; Prevention therapy; Principal Investigator; Protein Overexpression; Publishing; RANTES; Range; Reagent; Research; Research Personnel; Resources; Respiratory Tract Infections; Role; Severities; Solid; Stimulus; Students; Testing; Training; Training Programs; Transgenic Mice; Universities; Upper Respiratory Infections; Viral; Viral Genes; Virus; Virus Diseases; Work; abstracting; airway hyperresponsiveness; base; career; chemokine; chemokine receptor; defined contribution; design; experience; human disease; in vivo; member; mouse model; novel; pathogen; prevent; programs; research study; respiratory; response; skills; virology

DESCRIPTION (provided by applicant): This proposal outlines a five-year program to develop a career in academic medicine. The principal investigator will focus his efforts on developing the skills and experience in virology and immunology necessary to become an independent investigator. This program is based on a study of adenovirus pathogenesis, in particular the interactions between respiratory viral infection, pulmonary inflammation and airway hyperreactivity. Kathy Spindler, Ph.D., is an established investigator in the field of adenovirus pathogenesis and is a recognized expert in the mouse adenovirus type 1 (MAV-1) model used in this proposal. She has successfully trained postdoctoral fellows and graduate students and will mentor the principal investigator's scientific development. The principal investigator's scientific and career development will be enhanced by interactions with the members of his advisory committee, comprised of a group of investigators at the University of Michigan who are leaders in the fields of virology and pulmonary immunology. Their expertise will provide relevant support for the proposed research plan. Their vast mentoring experience will provide solid career guidance for the principal investigator. Research will focus on the interplay between adenovirus infection and host chemokine responses in the lung. The proposal uses MAV-1, providing the advantage of using a pathogen in its natural host, allowing for studies of both acute and persistent infection, and allowing the use of a vast array of reagents including knockout and transgenic mice. The proposed experiments will define the role of chemokine responses in the control of acute and persistent adenovirus infection and will determine the ability of Dersistent adenovirus infection to modulate host responses in the lung. The specific aims are: 1) define the roles of CCL5 and CCR5 in the pathogenesis of MAV-1 respiratory infection, and 2) determine whether Dersistent MAV-1 infection modulates pulmonary inflammation and airway hyperreactivity induced by subsequent inflammatory stimuli. The University of Michigan provides the ideal setting for this training program, with a wealth of physical and intellectual resources that maximize the principal investigator's Dotential to successfully establish a career as an independent investigator. Information resulting from this research will substantially increase our understanding of how adenovirus causes respiratory disease. In addition, these experiments will aid in solidifying links between persistent adenovirus infection and chronic lung diseases such as asthma and chronic obstructive pulmonary disease and have the potential to lead to virus-targeted therapies for the prevention or management of these conditions. (End of Abstract)

描述（由申请人提供）： 该提案概述了发展学术医学职业的五年计划。校长 调查员将集中精力培养成为独立调查员所需的病毒学和免疫学技能和经验。该计划基于对腺病毒发病机制的研究，特别是呼吸道病毒感染、肺部炎症和气道高反应性之间的相互作用。 Kathy Spindler 博士是腺病毒发病机制领域的知名研究者，也是小鼠领域公认的专家 本提案中使用 1 型腺病毒 (MAV-1) 模型。她成功地培养了博士后研究员和研究生，并将指导首席研究员的科学发展。首席研究员的科学和职业发展将通过与其咨询委员会成员的互动得到加强，该委员会由密歇根大学的一组研究人员组成，他们是病毒学和肺部免疫学领域的领导者。他们的专业知识将为拟议的研究计划提供相关支持。他们丰富的指导经验将为首席研究员提供坚实的职业指导。研究将集中于腺病毒感染与肺部宿主趋化因子反应之间的相互作用。该提案使用 MAV-1，提供了在其自然宿主中使用病原体的优势，允许研究急性和持续感染，并允许使用大量试剂，包括基因敲除小鼠和转基因小鼠。拟议的实验将确定趋化因子反应在控制急性和持续性腺病毒感染中的作用，并将确定持续性腺病毒感染调节肺部宿主反应的能力。具体目标是：1）定义 CCL5 和 CCR5 在 MAV-1 呼吸道感染发病机制中的作用，以及 2) 确定持续性 MAV-1 感染是否调节后续炎症刺激引起的肺部炎症和气道高反应性。密歇根大学为该培训计划提供了理想的环境，拥有丰富的体力和智力资源，可最大限度地发挥首席研究员的潜力，成功建立独立研究员的职业生涯。 这项研究产生的信息将大大增加我们对如何 腺病毒引起呼吸道疾病。此外，这些实验将有助于巩固持续性腺病毒感染与哮喘和慢性阻塞性肺病等慢性肺部疾病之间的联系，并有可能开发出用于预防或管理这些疾病的病毒靶向疗法。 （摘要完）