K24: Midcareer Investigator Award: Urban School Allergen Exposure and Childhood Asthma

K24：职业生涯中期研究员奖：城市学校过敏原暴露和儿童哮喘

• 批准号: 9920076
• 负责人: WANDA PHIPATANAKUL
• 金额: $ 18.93万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9920076
• 关键词: Address; Adverse effects; Affect; Allergens; Allergic Disease; Anatomy; Animals; Asthma; Award; Biological Markers; Blood; Cells; Cellular biology; Chemotaxis; Child; Childhood Asthma; Clinical; Clinical Research; Collaborations; Collection; Communities; Disadvantaged; Disease; Education; Encapsulated; Ensure; Environment; Environmental Exposure; Environmental Risk Factor; Epigenetic Process; Fostering; Functional disorder; Funding; Gender; Gene Expression; Genetic; Goals; Health; Home environment; Human; Hypersensitivity; Incidence; Inflammation; Inflammatory; Inflammatory Response; Infrastructure; Inhalation; Intervention; Intervention Studies; Intervention Trial; Investigation; Knowledge; Leukocytes; Localized Malignant Neoplasm; Location; Mediating; Membrane; Mentors; Messenger RNA; MicroRNAs; Molecular; Molecular Biology; Morbidity - disease rate; National Heart, Lung, and Blood Institute; National Institute of Allergy and Infectious Disease; Organ; Outcome; Particulate; Particulate Matter; Pathway interactions; Phenotype; Physicians; Pollution; Prediction of Response to Therapy; Productivity; Public Health; RNA; Research; Research Activity; Research Design; Research Personnel; Resources; Respiratory physiology; Role; Running; Saliva; Salivary; Schools; Scientist; Severities; Signal Transduction; Sleep; Source; Statistical Methods; Structure; Students; Symptoms; System; Techniques; Testing; Time; Tissues; Translations; United States; United States National Institutes of Health; Validation; Vesicle; Work; Youth; allergic airway disease; base; biomarker-driven; career development; cohort; cost; cytokine; data archive; design; disorder control; educational atmosphere; environmental intervention; extracellular; extracellular vesicles; immunoregulation; improved; inner city; longitudinal analysis; molecular marker; next generation; novel; novel marker; particle; particulate pollutant; patient oriented; patient oriented research; precision medicine; predicting response; predictive marker; programs; public health relevance; recruit; success; therapy design; urban school; vesicular release

Project Summary / Abstract Childhood asthma, particularly in urban environments, is a source of significant morbidity. Children spend the majority of their day in school. The immediate goal of this project is to determine the role of changes in school- specific environmental exposures and molecular biomarkers and asthma morbidity. The Candidate/PI is a physician scientist with expertise in patient oriented research and runs a fully NIH funded asthma/allergy clinical research center. Since this K-24 was awarded 4 years ago she has been extremely successful in mentoring by supporting 5 funded K-23 awards and expanding her program with her role as PI on 2 new U01s and 1 R01 with multiple other NIH funded clinical collaborations. This renewal is critical to maintaining this level of productivity and mentoring of the next generation of patient-oriented researchers. Her environment includes unparalleled community relationships, infrastructure, resources, and collaborators. Career Development Goals are to ensure that the candidate will be provided sufficient time for mentoring and patient oriented clinical research activities. The award will also allow her to further her education in statistical methods, study design, molecular biology, phenotype and endotype driven biomarker precision medicine, and environment interactions to help her expand her patient oriented research program. This will allow us to move towards our overall goal of further our understanding of molecular underpinnings in predicting treatment response and disease pathophysiology, which will allow her to develop and design interventions to reduce the severity and incidence of childhood asthma. The research hypothesis is that changes in classroom/school specific allergen/pollution levels will be associated with molecular extracellular vesicle (EV) changes and asthma morbidity. We will use a two stage validation approach to compare number, size, and miRNA cargo in saliva are associated with classroom levels of allergens and particulate pollutants and modified by the NIAID SICAS-2 school/classroom based environmental intervention and asthma health outcomes and compare them with data archived from SICAS-1 (our NIAID observational cohort). We will also compare these results in a subset of age/gender matched students without asthma as controls (the NHLBI funded EASY cohort) attending the same classrooms to further the interpretation of our findings utilizing state of the art techniques. The impact of this research may result in novel biomarkers that could inform us about the efficacy of school-based interventions against environmental exposures important to childhood asthma and its immune modulation, addressing a critical public health problem.

项目摘要/摘要 儿童哮喘，特别是在城市环境中，是严重发病率的一个来源。孩子们花在 他们一天的大部分时间都在学校。这个项目的直接目标是确定学校变革的作用- 特定环境暴露和分子生物标志物与哮喘发病率。应聘者/PI是 内科科学家，在以患者为中心的研究方面具有专业知识，并经营着由NIH全额资助的哮喘/过敏项目 临床研究中心。自从4年前获得K-24证书以来，她在 通过支持5个资助的K-23奖项和扩展她的项目，在2个新的U01上扮演PI的角色进行指导 和1个R01，与NIH资助的多个其他临床协作。这一更新对于保持这一点至关重要 下一代以患者为中心的研究人员的工作效率和指导水平。她所处的环境 包括无与伦比的社区关系、基础设施、资源和协作者。职业生涯 发展目标是确保候选人有足够的时间进行指导和耐心 以临床研究活动为导向。该奖项还将允许她继续在统计方法方面的教育， 研究设计，分子生物学，表型和内型驱动的生物标记物精密医学，以及 环境互动，帮助她扩大以病人为中心的研究计划。这将允许我们移动 我们的总体目标是进一步了解分子基础在预测治疗中的作用 反应和疾病病理生理学，使她能够开发和设计干预措施，以减少 儿童哮喘的严重程度和发病率。研究假设是教室/学校的变化 特定的过敏原/污染水平将与分子细胞外小泡(EV)的变化和 哮喘发病率。我们将使用两阶段验证方法来比较数量、大小和miRNA货物 唾液中的过敏原和颗粒污染物与教室中的过敏原和颗粒污染物水平有关，并被NIAID修改 SICAS-2学校/教室环境干预与哮喘健康结局的比较 这些数据来自SICAS-1(我们的NIAID观测队列)。我们还将比较这些 结果在年龄/性别匹配的没有哮喘的学生中作为对照组(NHLBI资助的Easy 队列)参加相同的教室，以进一步解释我们的发现，利用最先进的技术 技巧。这项研究的影响可能导致新的生物标志物，可以告诉我们关于 以学校为基础的干预措施对儿童哮喘和儿童重要环境暴露的有效性 它的免疫调节，解决了一个关键的公共卫生问题。