This career development award will provide Emily McGowan, MD with the skills, knowledge, and mentored research experience that are essential for an independent career as a clinician scientist in the field of allergy and immunology. Food allergy (FA) is a common childhood disease that appears to have increased in prevalence over the past two decades. The interplay between genes and the environment likely plays a key role in the development of FA, and DNA methylation is one possible mechanism by which environmental influences may affect gene expression. Several nutrients, including folate, vitamin B12, and choline, are involved in the one carbon metabolism pathway (OCMP), in which a methyl donor is transferred to DNA. In two separate cohorts, our group has shown an association between higher serum folate levels and the development of allergic sensitization, leading to our central hypothesis that differential exposure to folate, B12, and choline is associated with the development of food sensitization (FS) and FA, and that this is mediated by changes in DNAm. Dr. McGowan proposes to explore this hypothesis by examining 1) whether pre-natal or post-natal exposure to these OCMP micronutrients is independently associated with FS and FA; 2) whether differential exposure to these OCMP micronutrients is associated with DNA methylation; and 3) whether differentially methylated genes are associated with the development of FS and FA. In order to address these questions, Dr. McGowan will use two study populations: 1) a nested case-control study of children within the well-characterized Boston Birth Cohort (BBC) and 2) a new prospective cohort of 100 children at high risk for developing FA. Given the widespread exposure to methyl donors through formula and supplements in infancy, the results of this study could have major public health implications. In addition, this K23 award will provide Dr. McGowan with opportunities for advanced training in epidemiology, including the completion of a PhD in Clinical Investigation at the Johns Hopkins Bloomberg School of Public Health (JHBSPH). She will also pursue training to develop new skills in the analysis and interpretation of epigenomic data. Dr. McGowan plans to achieve these goals through formal coursework, workshops, national meetings, and mentored research. Her primary mentor for this award is Dr. Xiaobin Wang, a molecular epidemiologist who studies genetic and environmental predictors of childhood health. Her mentoring team further includes Drs. Robert Wood, Elizabeth Matsui, Corinne Keet, Daniele Fallin, and Kasper Hansen, experts in food allergy, epidemiology, epigenetics, and statistics. This training plan, and the data generated from this proposed project, will provide the foundation needed to successfully transition to the role of an independent clinician scientist studying the epidemiology and treatment of food allergy.

Public Health Relevance

Food allergy is a common childhood condition that appears to have increased in prevalence over the past two decades. This proposed study will address the important question of whether increased exposure to dietary methyl donors leads to changes in DNA methylation, and ultimately, allergic disease. Given the widespread exposure to methyl donors through formula and supplements in early life, the results of this study could have major public health implications.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23AI123596-02
Application #
9411078
Study Section
Allergy, Immunology, and Transplantation Research Committee (AITC)
Program Officer
Gondre-Lewis, Timothy A
Project Start
2017-01-10
Project End
2020-12-31
Budget Start
2018-01-01
Budget End
2018-12-31
Support Year
2
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Virginia
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
065391526
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
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Schuyler, Alexander J; Tripathi, Anubha; Workman, Lisa J et al. (2018) Underestimation of specific IgE measurements using extract-based assays on undiluted sera revealed through dilution. J Allergy Clin Immunol Pract 6:1070-1072.e4
Lawrence, Monica G; Palacios-Kibler, Thamiris V; Workman, Lisa J et al. (2018) Low Serum IgE Is a Sensitive and Specific Marker for Common Variable Immunodeficiency (CVID). J Clin Immunol 38:225-233
Wilson, Jeffrey M; McGowan, Emily C (2018) Diagnosis and Management of Eosinophilic Esophagitis. Immunol Allergy Clin North Am 38:125-139
Wilson, Jeffrey M; Workman, Lisa; Schuyler, Alexander J et al. (2018) Allergen sensitization in a birth cohort at midchildhood: Focus on food component IgE and IgG4 responses. J Allergy Clin Immunol 141:419-423.e5