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.

Project Narrative Ascariasis (roundworm) is the most common intestinal parasitic infection globally and causes severe life-long illness in children. The larval stage ascariasis can cause an asthma-like allergic airway disease. This proposal will identify the immunologic mechanisms of Ascaris-induced allergic airway disease in order to develop interventions that are urgently needed to prevent significant illness in children globally.