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

摘要：Weatherhead博士是儿科热带医学和传染病的助理教授 他是贝勒医学院(BCM)的教授，也是免疫寄生虫学领域的内科科学家。她的事业 目标是成为寄生虫健康差距方面的专家，并进行高质量的基础科学研究 改善贫困儿童的健康状况。生活贫困的儿童感染寄生虫的风险很高。 例如蛔虫病，它感染了8亿多儿童，并与显著的发病率有关，包括 过敏性呼吸道疾病。Weatherhead博士的目标是剖析对蛔虫病的复杂宿主免疫反应 以突出迫切需要的新干预措施，以防止贫困儿童的发病率。 她独特的技能组合将使她成为实验室发现和现场实施 新开发的驱虫药靶标。为了实现这些目标，韦瑟黑德博士开发了一种 全面的职业发展计划，将全面的指导和培训活动相结合 加入她的基础研究和翻译研究项目。她将安排与她的投资人会面 导师团队，分子免疫学和过敏性呼吸道疾病方面的权威大卫·科里博士和大卫·科里博士。 寄生虫学和疫苗开发领域的全球领先者彼得·霍特兹说。Weatherhead博士将收到额外的 来自她的科学咨询委员会的关于微生物-宿主免疫接口的专家级指导。 辅导性研究将辅之以正式培训活动，包括研究生水平的课程工作， 参加国家科学会议并指导科学交流和学术 领导力。她的职业发展计划得到了世界级的科学环境的支持，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和获得性免疫机制 蛔虫幼虫肺部移行可引起过敏性呼吸道疾病。第一个目标将定义分子途径。 参与肺蛔虫病时的先天免疫激活。第二个目标将决定时间和目标 由于蛔虫诱导的适应性免疫，宿主失去外周免疫耐受的时间 激活。这两个目标都将评估存在和不存在蛋白酶活性时的免疫途径。 这项提案中概述的问题对热带医学和寄生虫学领域具有重要意义。 有可能改变我们对复杂的寄生虫-宿主关系的理解，为 假设蛔虫病是流行地区过敏性呼吸道疾病的主要原因。这项提议将 提高对蛔虫性过敏性呼吸道疾病发病机制的认识 提供对哮喘的总体治疗洞察力，建议关键的新干预靶点 这是预防儿童发病所必需的。本报告建议的辅导式职业发展活动 申请将使Weatherhead博士成为免疫寄生虫学的独立研究员。

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.