Mentoring patient-oriented researchers in inflammatory airway disease

指导炎症性气道疾病领域以患者为中心的研究人员

基本信息

批准号：
10657746
负责人：
TAYLOR A DOHERTY
金额：
$ 19.37万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-07-01 至 2027-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10657746
关键词：
ACVR1 gene Affect Airway Disease Allergic Allergic Disease Allergic rhinitis Animal Model Aspirin Asthma Award Bioinformatics Biological Biological Products Biological Response Modifier Therapy Blood Cellular biology Chronic Clinic Clinical Clinical Investigator Clinical Trials Cluster Analysis Coculture Techniques Color Conduct Clinical Trials Discipline Disease Eicosanoids Eosinophilic Esophagitis Epithelial Cells Faculty Flow Cytometry Fostering Funding Future Goals Health Care Costs Human Hypersensitivity Immunology In Vitro Individual Inflammation Inflammatory Interleukin 4 Receptor Interleukin-13 Interleukin-4 Interleukin-5 Laboratories Letters Leukocytes Lipids Lung Lymphoid Cell Mediating Mentors Mentorship Mid-Career Clinical Scientist Award (K24)Migration Assay Mission Morbidity - disease rate Nasal Polyps Nature Nose Otolaryngology Pathogenesis Pathway interactions Patients Pattern Population Prostaglandin D2 Reaction Research Research Personnel Research Proposals Research Training Role STAT6 gene Sampling Scientist Severities Signal Transduction Sinus Sputum Structure of mucous membrane of nose Subgroup Symptoms Technology Testing Time Tissues Training Vocational Guidance Work airway epithelium airway inflammation antagonist anti-IgE aspirin-exacerbated respiratory disease asthmatic biobank career chemokine chronic rhinosinusitis clinical care clinical predictors cyclooxygenase 1 cytokine eosinophil in vivo inhibitor inter-institutional lipidomics medical specialties migration next generation novel patient oriented patient oriented research peripheral blood prevent profiles in patients recruit reduce symptoms respiratory response sample collection single-cell RNA sequencing standard of care statistics therapeutic target transcriptome transcriptomics treatment response

项目摘要

Abstract The overall goal of the proposed research is to identify novel aspects of human innate lymphoid cell (ILC) biology in airway diseases using patient-oriented research (POR) and through mentoring junior clinical investigators. The candidate has a strong record of mentoring individuals at many levels including clinical investigators in multiple specialties. The mentoring plan includes recruitment and training of fellow and faculty investigators from three disciplines (allergy, otolaryngology, and pulmonary) within the UCSD Center for Asthma and Sinus Disease center of excellence to foster the careers of junior investigators and perform outstanding POR. There are currently large gaps in our understanding of the roles of ILCs in human sinus disease and asthma which cause significant morbidity worldwide. ILCs are divided by the types of cytokines they secrete and ILC2s that secrete Th2 cytokines have been shown to promote airway inflammation in animal models. Importantly, recent work has shown that ILC2s are increased in samples from patients with asthma and chronic rhinosinusitis (CRS). Our group was the first to show that ILC2s are increased in a subgroup of nasal polyps in CRS that contain eosinophils and are also recruited to the nose after aspirin challenge in patients with aspirin-exacerbated respiratory disease (AERD). AERD patients have severe sinus disease with nasal polyps, moderate to severe asthma, and respiratory reactions to aspirin and similar compounds. In the current proposal, we will test the hypothesis that through the use of cutting-edge technology (single cell RNA-seq) we will be able to identify specific subgroups or “endotypes” of patients with CRS and asthma by tissue and blood ILC subset composition. We also posit that biologic blockade of type 2 inflammation in AERD, asthma and CRS patients will reduce ILC2 recruitment to the airway. Critically, this award will provide protected time for POR in sinus disease and asthma and allow for outstanding mentorship of the next generations of POR investigators.

抽象的拟议研究的总体目标是确定人类先天淋巴机构的新方面使用以患者为导向的研究（POR）和通过心理少年进行气道疾病中的细胞（ILC）生物学临床研究人员。候选人在许多层面上都有精神上的人的记录，包括多个专业的临床研究人员。心理计划包括招募和培训来自UCSD的三个学科（过敏，耳鼻喉科和肺部）的教师调查员哮喘和鼻窦病卓越中心，以培养初级调查人员的职业并执行出色的POR。目前，我们对ILC的角色的理解有很大的差距在人类鼻窦病和哮喘中，全世界引起了明显的发病率。 ILC由它们秘密的细胞因子类型和秘密Th2细胞因子的ILC2被证明可以促进动物模型中的气道注射。重要的是，最近的工作表明ILC2在来自哮喘和慢性鼻窦炎（CRS）患者的样本。我们的小组是第一个展示的在含有嗜酸性粒细胞的CR中，ILC2在鼻息音的亚组中增加了阿司匹林挑战后，阿司匹林呼吸道疾病的患者被招募到鼻子（Aerd）。 AERD患者患有严重的鼻窦疾病，患有鼻息肉，中度至重度哮喘和对阿司匹林和类似化合物的呼吸反应。在当前的建议中，我们将检验假设通过使用尖端技术（单细胞RNA-seq），我们将能够确定特定的通过组织和血液ILC子集组成的CRS和哮喘患者的亚组或“内型”。我们还确认，AERD，哮喘和CRS患者的2型炎症的生物阻塞将将ILC2招募减少到气道。至关重要的是，该奖项将为鼻窦的POR提供受保护的时间疾病和哮喘，并允许下一代POR研究者的出色心态。