Variant Nucleotide Receptor Function in Airway Disorders

气道疾病中的变异核苷酸受体功能

• 批准号: 7384659
• 负责人: Loren C Denlinger
• 金额: $ 14.26万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7384659
• 关键词: Acute; Affect; Agonist; Alleles; Alveolar Macrophages; Asthma; Attenuated; Basic Science; Businesses; Chlamydophila pneumoniae; Chronic; Clinical Investigator; Clinical Research; Clinical Trials; Condition; Databases; Development; Development Plans; Diagnosis; Disease; Educational Status; Educational workshop; Environment; Epidemiologic Methods; Evaluation; Eye; Functional disorder; Funding; Future; Genes; Goals; Grant; High Prevalence; Human; Immune; Immune response; Infection; Interleukin-10; Language; Leadership; Link; Medicine; Mentors; Modification; Morbidity - disease rate; Needs Assessment; Nucleotides; Patients; Pharmacogenomics; Pharmacology; Phenotype; Population; Protocols documentation; Range; Rate; Research Infrastructure; Risk Factors; Role; Scientist; Screening procedure; Shapes; Sputum; Testing; Training; Training Activity; Translating; Universities; Variant; Wisconsin; asthmatic patient; career; experience; interest; loss of function; macrophage; methacholine; pathogen; programs; receptor; receptor function; respiratory; response; skills; tool

DESCRIPTION (provided by applicant): The goal of this proposal is the advanced training of Dr. Loren Denlinger to complete his transition from a basic scientist to an academic clinical investigator in airway diseases. The long range Career Goal is to become an independently funded clinical investigator with local and national leadership potential, focusing on airway disorders linked epidemiologically to respiratory pathogens, and with a view towards personalized- medicine for the diagnosis and treatment of these infections. The Objectives for this proposal are to 1) become practically familiar with the skills needed for asthma phenotyping, 2) utilize epidemiological methods to translate basic science findings to clinical research hypotheses, and 3) develop project management, leadership, and business skills. The Career Development plan proposes a combination of new didactic courses, workshops, and practicum experiences, taking advantage of the established infrastructure in needs assessment, development planning and evaluation of the University of Wisconsin Clinical Investigator Preparatory Program. The Mentoring Committee has been restructured to include new intellectual influences to shape Dr. Denlinger's clinical research skills development, and a detailed plan with each mentor synchronizing training activities. This will take place within the rich environment provided by the University of Wisconsin and the NHLBI Asthma Clinical Research Center. The scientific focus is on the host-specific variability in the immune response to intracellular respiratory pathogens that contribute to the acute and chronic pathophysiology of asthma. Generally stated, the hypothesis is that the nucleotide receptor P2X7 is part of a set of innate immune factors important to the acute and chronic clearance of intracellular pathogens. Ancillary protocols to the Sponsor and Co-Sponsor's grant and clinical trial provide the means to test a functional screening tool for P2X7 activity within epidemiological databases and assess its role as a risk factor in both acute and chronic asthma. Pharmacogenomic analysis of the P2X7 responses of primary alveolar macrophages will also be performed with an eye toward risk factor modification in future clinical trials. In lay-language summary, this proposal will promote high-level training of a new clinical investigator interested in developing new patient-specific therapies for asthma, a condition affecting 7% of the U.S. population with an increasing prevalance and morbidity.

描述（由申请人提供）：该提案的目的是对Loren Denlinger博士的高级培训，以完成他从基本科学家到气道疾病的学术临床研究者的过渡。远程职业生涯的目标是成为具有本地和国家领导潜力的独立资助的临床研究者，重点是在流行病学上与呼吸道病原体相关的气道疾病，并观察到个性化医学 - 用于诊断和治疗这些感染。该提案的目标是1）实际上熟悉哮喘表型所需的技能，2）利用流行病学方法将基础科学发现转化为临床研究假设，以及3）发展项目管理，领导力和业务技能。职业发展计划提出了新的教学课程，讲习班和实践经验的结合，利用了威斯康星大学临床研究人员预备计划的需求评估，开发计划和评估的既定基础设施。指导委员会被重组为包括新的智力影响，以塑造Denlinger博士的临床研究技能发展，并与每位导师同步培训活动进行详细计划。这将发生在威斯康星大学和NHLBI哮喘临床研究中心提供的丰富环境中。科学的重点是对细胞内呼吸道病原体的免疫反应的宿主特异性变异性，这有助于哮喘的急性和慢性病理生理。通常，假设是核苷酸受体P2X7是对细胞内病原体急性和慢性清除重要的一组先天免疫因子的一部分。赞助商和共同赞助商的赠款和临床试验的辅助方案提供了测试流行病学数据库中P2X7活性的功能筛查工具的手段，并评估其作为急性和慢性哮喘的危险因素的作用。对原发性肺泡巨噬细胞的P2X7反应的药物基因组学分析也将在未来的临床试验中注视风险因素。在外行摘要中，该提案将促进对有兴趣开发新的患者特异性疗法的新临床研究者的高级培训，这种疾病影响了7％的美国人群，患病和发病率的增加。