Discovering the Immunologic Mechanism of Ascaris-induced Allergic Airway Disease.

发现蛔虫引起的过敏性气道疾病的免疫机制。

基本信息

批准号：
10563160
负责人：
Jill Elizabeth Weatherhead
金额：
$ 18.75万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-02-20 至 2025-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10563160
关键词：
Acceleration Accounting Adaptive Immune System Advisory Committees Allergens Antigens Area Ascariasis Ascaris Asthma Attenuated Authorization documentation Basic Science Cell physiology Cells Child Child Health Childhood Communicable Diseases Communication Complex Comprehension Data Development Development Plans Dissection Environment Extrinsic asthma Fibrinogen Goals Helper-Inducer T-Lymphocyte Hospitalization Host-Parasite Relations IgE Immune Immune Tolerance Immune response Immunologics Infection Inflammatory Ingestion Innate Immune Response Innate Immune System Instruction Interleukin-13 Interleukin-4 Interleukin-5 Intervention Intestines Investments K-Series Research Career Programs Laboratories Larva Leadership Ligands Link Lung Mediating Medicine Mentors Mentorship Molecular Molecular Immunology Morbidity - disease rate Mus Nematoda Parasitic infection Parasitology Pathogenesis Pathway interactions Peptide Hydrolases Peripheral Persons Phenotype Physicians Poverty Regulatory T-Lymphocyte Research Research Personnel Research Proposals Resolution Resources Role STAT6 Transcription Factor Schedule Scientist Signal Transduction Symptoms TLR4 gene Teacher Professional Development Th2 Cells Therapeutic Training Activity Translational Research Tropical Medicine United States National Institutes of Health Vaccines adaptive immune response airway hyperresponsiveness allergic airway disease asthma model authority career career development college cytokine egg fungus health disparity helminth infection high risk immune activation improved innovation insight meetings microbial microbial host migration mouse model new therapeutic target novel pathogen prevent professor response skills translational research program vaccine development

项目摘要

Summary: Dr. Weatherhead is an Assistant Professor of Pediatric Tropical Medicine and Infectious Diseases at Baylor College of Medicine (BCM) and a physician-scientist in the area of immunoparasitology. Her career goal is to be an expert in parasitic health disparities and perform high-quality basic science research that improves the health of children living in poverty. Children living in poverty are at high risk of parasitic infections such as ascariasis, which infects over 800 million children and is associated with significant morbidity including allergic airway disease. Dr. Weatherhead aims to dissect the complex host immune response to ascariasis in order to highlight novel interventions that are urgently needed to prevent morbidity in children living in poverty. Her unique skill set will allow her to serve as a link between laboratory discovery and field implementation of newly developed anthelminthic targets. To accomplish these goals, Dr. Weatherhead has developed a comprehensive career development plan which combines thorough mentoring and training activities integrated into her basic and translational research program. She will have scheduled meetings with her invested mentorship team, Dr. David Corry, an authority in molecular immunology and allergic airway disease, and Dr. Peter Hotez, a global leader in parasitology and vaccine development. Dr. Weatherhead will receive additional expert-level mentorship on the microbial-host immune interface from her scientific advisory committee. Mentored research will be supplemented with formal training activities including graduate-level coursework, participation in national scientific meetings and instruction in scientific communication and academic leadership. Her career development plan is supported by a world-class scientific environment which offers ample opportunities for junior faculty development and provides all the resources needed to achieve her career goals. Dr. Weatherhead's research will evaluate the innate and adaptive immunologic mechanism by which Ascaris larval lung migration induces allergic airway disease. The first aim will define the molecular pathway involved in innate immune activation during pulmonary ascariasis. The second aim will determine when and for how long the host loses peripheral immune tolerance as a result of Ascaris-induced adaptive immune activation. Both aims will evaluate the immune pathways in the presence and absence of protease activity. Questions outlined in this proposal are highly significant to the field of tropical medicine and parasitology having the potential to shift our understanding of the complex parasite-host relationship, lending support to the hypothesis that ascariasis is a leading cause of allergic airway disease in endemic regions. This proposal will advance the comprehension of the mechanistic pathways of Ascaris-induced allergic airway disease as well as provide therapeutic insight into asthma in general, suggesting novel interventional targets that are critically needed to prevent morbidity in children. The mentored career development activities proposed in this application will allow Dr. Weatherhead to evolve as an independent investigator in immunoparasitology.

摘要：Weatherhead 博士是小儿热带医学和传染病助理教授贝勒医学院 (BCM) 博士，免疫寄生虫学领域的医师科学家。她的事业目标是成为寄生虫健康差异方面的专家并进行高质量的基础科学研究改善贫困儿童的健康。贫困儿童感染寄生虫的风险很高例如蛔虫病，它感染了超过 8 亿儿童，并与多种疾病相关，包括过敏性气道疾病。 Weatherhead 博士旨在剖析宿主对蛔虫病的复杂免疫反应旨在强调为预防贫困儿童发病而迫切需要的新干预措施。她独特的技能将使她能够成为实验室发现和现场实施之间的纽带新开发的驱虫目标。为了实现这些目标，Weatherhead 博士开发了一种全面的职业发展计划，结合了全面的指导和培训活动进入她的基础和转化研究计划。她将与她的投资人安排会面导师团队由分子免疫学和过敏性气道疾病领域权威David Corry博士和 Peter Hotez，寄生虫学和疫苗开发领域的全球领导者。韦瑟黑德博士将获得额外的她的科学顾问委员会对微生物-宿主免疫界面提供专家级指导。指导研究将辅以正式的培训活动，包括研究生水平的课程、参加国家科学会议以及科学传播和学术指导领导。她的职业发展计划得到了世界一流的科学环境的支持，该环境提供了为初级教师提供充足的发展机会，并提供实现其职业生涯所需的所有资源目标。 Weatherhead 博士的研究将评估先天性和适应性免疫机制，通过该机制蛔虫幼虫肺部迁移诱发过敏性气道疾病。第一个目标将定义分子途径参与肺蛔虫病期间的先天免疫激活。第二个目标将决定何时以及为了什么宿主因蛔虫诱导的适应性免疫而失去外周免疫耐受需要多长时间激活。这两个目标都将评估存在和不存在蛋白酶活性的情况下的免疫途径。本提案中概述的问题对于热带医学和寄生虫学领域非常重要有潜力改变我们对复杂的寄生虫与宿主关系的理解，为假设蛔虫病是流行地区过敏性气道疾病的主要原因。该提案将促进对蛔虫引起的过敏性气道疾病以及过敏性气道疾病的机制途径的理解提供对哮喘的总体治疗见解，提出关键的新干预目标需要预防儿童发病。本报告中提出的指导性职业发展活动该应用程序将使 Weatherhead 博士成为免疫寄生虫学领域的独立研究者。