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: 7790598
• 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/7790598
• 关键词: 12q24; Acute; Adenine Nucleotides; Affect; Agonist; Alleles; Alveolar Macrophages; Asthma; Attenuated; Basic Science; Biological; Biological Assay; Biological Markers; Blood specimen; Bronchoscopy; Businesses; Cations; Characteristics; Chlamydia; Chlamydophila pneumoniae; Chronic; Clinical; Clinical Investigator; Clinical Research; Clinical Trials; Data; Databases; Development; Development Plans; Diagnosis; Dilatation - action; Disease; Educational Status; Educational workshop; Environment; Epidemiologic Methods; Epidemiology; Epithelial Cells; Evaluation; Eye; Functional disorder; Funding; Future; Genes; Goals; Grant; High Prevalence; Human; Immune; Immune response; Immunity; Immunoglobulin A; Individual; Infection; Institutes; Integration Host Factors; Interleukin-10; Language; Leadership; Leukocytes; Ligands; Link; Mediator of activation protein; Medicine; Mentors; Metabolic Clearance Rate; Modeling; Modification; Morbidity - disease rate; Mycobacterium tuberculosis; National Heart, Lung, and Blood Institute; Natural Immunity; Needs Assessment; Neutrophilia; Patients; Performance; Permeability; Pharmacogenomics; Pharmacology; Phenotype; Phospholipase D; Population; Positioning Attribute; Production; Proteins; Protocols documentation; Recording of previous events; Regulation; Research; Research Infrastructure; Research Personnel; Resolution; Risk; Risk Factors; Role; Safety; Sample Size; Scientist; Screening procedure; Shapes; Signal Transduction; Sputum; Structure of respiratory epithelium; Symptoms; Testing; Tissues; Training; Training Activity; Translating; Universities; Up-Regulation; Upper Respiratory Infections; Variant; Whole Blood; Wisconsin; airway hyperresponsiveness; asthmatic patient; career; career development; cytokine; experience; extracellular; interest; loss of function; macrophage; methacholine; nucleotide receptor; pathogen; patient population; 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）：本申请的目标是对Loren Denlinger博士进行高级培训，以完成他从基础科学家到气道疾病学术临床研究者的过渡。长期的职业目标是成为一名具有地方和国家领导潜力的独立资助的临床研究者，专注于与呼吸道病原体相关的流行病学气道疾病，并着眼于诊断和治疗这些感染的个性化药物。本计划书的目标是：1)实际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；3)发展项目管理、领导和商业技能。职业发展计划提出了新的教学课程、研讨会和实习经验的结合，利用了威斯康星大学临床研究者预备项目在需求评估、发展规划和评估方面的既定基础设施。指导委员会已经重组，以包括新的智力影响，以塑造Denlinger博士的临床研究技能发展，并与每个导师同步培训活动的详细计划。这将在威斯康星大学和NHLBI哮喘临床研究中心提供的丰富环境中进行。科学的重点是宿主对细胞内呼吸道病原体的免疫反应的特异性变异性，这些病原体有助于哮喘的急性和慢性病理生理。一般来说，假设是核苷酸受体P2X7是一组对细胞内病原体的急性和慢性清除很重要的先天免疫因子的一部分。申办者和共同申办者的资助和临床试验的辅助方案提供了在流行病学数据库中测试P2X7活性功能筛查工具的方法，并评估其作为急性和慢性哮喘风险因素的作用。原代肺泡巨噬细胞P2X7反应的药物基因组学分析也将在未来的临床试验中进行，着眼于风险因素的改变。简而言之，该提案将促进对新的临床研究者的高水平培训，这些研究者对开发针对哮喘的新的患者特异性疗法感兴趣，哮喘影响了美国7%的人口，并且患病率和发病率都在增加。