The principal investigator has already demonstrated a strong commitment to a career in clinical investigation and her goal is to utilize epidemiologic methods to extend current knowledge of the relationship between allergen exposure and the pathogenesis of allergic sensitization. A detailed understanding of this relationship will ultimately drive the development of strategies to prevent allergic sensitization. To meet the career goals, the principal investigator has ? proposed a career development plan that includes mentoring by experts in allergen exposure, immunology, study design, and longitudinal data analysis. In addition, the principal investigator has completed all requirements for a Master's of Health Science in Epidemiology, and will take additional courses in longitudinal data analysis, cohort study design, and exposure assessment. The expertise of the mentors and the didactic coursework complement the proposed research project which builds on preliminary work and will provide the principal investigator with invaluable experience in allergen exposure assessment, quantification of allergen-specific immune responses, and the design, conduct and analysis of prospective cohort studies. ? Using occupational mouse allergy as a model, the principal investigator proposes to study the relationship between mouse allergen exposure and immunologic responses using a prospective cohort study of laboratory mouse workers to 1) determine if the phenotype of the mouse-specific T lymphocyte cytokine responses is associated with the level of mouse allergen exposure, 2) determine if mouse allergen-specific cytokine responses are associated with particular mouse-specific IgG subclasses, and 3) determine if mouse allergen-specific IgG4 predicts the development of IgE mediated ? mouse sensitization. She specifically aims to determine if high levels of exposure result in mouse allergen induced upregulation of T lymphocyte IL-10 gene expression, and whether the development of a mouse-specific IL-10 response, in turn, promotes the production of mouse-specific IgG4 instead of IgE. A prospective cohort study of the relationship between exposure and sensitization would provide the data that is critically needed for developing scientifically sound approaches to primary prevention of allergic sensitization. In addition, improvements in the prediction of allergic sensitization would allow interventions to be targeted in a more practical and efficient manner to those at highest risk. ? ? ? ?
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