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

• 批准号: 10515489
• 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
• 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/10515489
• 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; Lead; 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

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.

摘要 这项拟议研究的总体目标是确定人类先天淋巴的新方面。 应用以患者为中心的研究(POR)和通过指导青少年在呼吸道疾病中的细胞(ILC)生物学 临床调查员。应聘者有在多个层面指导个人的良好记录，包括 多个专业的临床研究人员。导师计划包括招募和培训研究员 和来自加州大学圣迭戈分校三个学科(过敏、耳鼻喉科和肺科)的教职调查人员 哮喘和鼻窦疾病卓越中心促进初级调查人员的职业生涯 并表现出色的POR。目前，我们对国际法委员会的作用的理解存在很大差距 在人类鼻窦疾病和哮喘方面，这两种疾病在世界范围内造成了显著的发病率。ILC除以 它们分泌的细胞因子类型和分泌Th2细胞因子的ILC2已被证明促进 动物模型中的呼吸道炎症。重要的是，最近的研究表明，ILC2在 哮喘和慢性鼻窦炎(CRS)患者的样本。我们的团队是第一个展示 在CRS中含有嗜酸性粒细胞的鼻息肉亚群中ILC2增加，而且 阿司匹林加重的呼吸系统疾病患者在阿司匹林挑战后被招募到鼻腔 (AERD)。AERD患者有严重的鼻窦疾病和鼻息肉，中度到重度哮喘，以及 对阿司匹林和类似化合物的呼吸道反应。在目前的提案中，我们将检验这一假设 通过使用尖端技术(单细胞rna-seq)，我们将能够识别特定的 CRS和哮喘患者按组织和血液ILC亚群组成的亚型或“内型”。 我们还假设，对AERD、哮喘和CRS患者2型炎症的生物阻断将 减少ILC2在呼吸道的募集。关键的是，这个奖项将为POR在鼻窦中提供保护时间 疾病和哮喘，并为下一代POR调查人员提供出色的指导。