Adenovirus modulation of pulmonary inflammation

描述(由申请人提供)： 这项提案概述了一项为期五年的计划，以发展学术医学事业。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方面的技能和经验。这个项目是基于对腺病毒致病机制的研究，特别是呼吸道病毒感染、肺部炎症和呼吸道高反应性之间的相互作用。凯西·斯宾德勒博士是腺病毒致病机制领域的知名研究者，也是公认的小鼠专家。 本提案中使用的腺病毒1型(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。首席研究人员的科学和职业发展将通过与他的咨询委员会成员的互动来促进，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调查员提供坚实的职业指导。研究将集中在腺病毒感染和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，允许对急性和持续感染进行研究，并允许使用包括基因敲除和转基因小鼠在内的大量试剂。拟议的实验将确定趋化因子反应在控制急性和持续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)界定 CCL5和CCR5在MAV-1呼吸道感染发病机制中的作用；2)确定持续MAV-1感染是否调节由随后的炎症刺激引起的肺部炎症和呼吸道高反应性。密歇根大学为这一培训项目提供了理想的环境，拥有丰富的体力和智力资源，最大限度地发挥首席调查员的潜质，成功地建立了作为独立调查员的职业生涯。 从这项研究中获得的信息将大大增加我们对 腺病毒会引起呼吸道疾病。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疾病等慢性肺部疾病之间的联系，并有可能导致针对病毒的治疗，以预防或管理这些疾病。 (摘要结束)

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)