Common underlying biologic pathways link allergic diseases such as asthma, allergic rhinitis, allergic dermatitis, and eosinophilic esophagitis with the epithelium being a nexus. Each of these diseases has been associated with genetic variation;further some genes have been implicated across multiple allergic diseases. While this work clearly points to some shared underlying genetic effects, identification of variants which predispose individuals to specific allergic disease could advance therapeutic treatments and improve prediction. The overall objective of this U19 is to elucidate the mechanisms by which epithelial cells contribute to the pathogenesis of allergic disorders. The overarching hypothesis of this Center proposal is that epithelial cell genes play a central role in the pathogenesis of allergic disorders. As the Data Integration and Analysis core, our objective is to provide the quantitative expertise to accomplish the overall objective. The rationale for this core is that to synthesize information across the individual projects, data must be analyzed in a consistent manner. This component does not have its own scientific aims but its expertise in quantitative genetics, genomics, statistics, and epidemiology creates the capacity for rigorous research that will be applied to advance the goals of the overall Center as well as assist the project investigators with their specific hypotheses and aims.
The specific aims of this core are therefore as follows: 1) To provide statistical genetic expertise for analyses proposing to elucidate the associations between epithelial genes and allergic disorders, 2) To integrate results from the three Center projects in order to further clarify the shared and unique contributions of epithelial genes in allergic diseases, 3) To validate findings utilizing multiple well-established public and private cohorts. The successful completion of the proposed studies will identify shared and unique pathways of diverse allergic diseases (asthma, allergic rhinitis, allergic dermatitis, and eosinophilic esophagitis). Clinically, this research is significant as we expect that this work will help delinieate the relationship of pathways related to allergic disease states and ultimately identify therapeutic targets which will have individualized effects. Further, this research is innovative as the targeted focus on the genetics of the epithelium across disease influencing different musocal surfaces (lung, Gl tract, skin) is an innovative approach which will reduce multiple testing while increasing the biologic interpretability of the findings.

Public Health Relevance

The proposed research is relevant to public health because identifying shared and unique genetic influences of allergic disorders will improve our understanding of the impact of therapies across disease states. Thus, the proposed research is relevant to NIH's mission because it will provide fundamental knowledge necessary to improve treatment of allergic disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
2U19AI070235-06
Application #
8196248
Study Section
Special Emphasis Panel (ZAI1-PA-I (M1))
Project Start
2011-07-01
Project End
2016-06-30
Budget Start
2011-09-01
Budget End
2012-08-31
Support Year
6
Fiscal Year
2011
Total Cost
$172,369
Indirect Cost
Name
Cincinnati Children's Hospital Medical Center
Department
Type
DUNS #
071284913
City
Cincinnati
State
OH
Country
United States
Zip Code
45229
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Johansson, Elisabet; Biagini Myers, Jocelyn M; Martin, Lisa J et al. (2017) KIF3A genetic variation is associated with pediatric asthma in the presence of eczema independent of allergic rhinitis. J Allergy Clin Immunol 140:595-598.e5
Caldwell, Julie M; Paul, Misu; Rothenberg, Marc E (2017) Novel immunologic mechanisms in eosinophilic esophagitis. Curr Opin Immunol 48:114-121
Caldwell, J M; Collins, M H; Kemme, K A et al. (2017) Cadherin 26 is an alpha integrin-binding epithelial receptor regulated during allergic inflammation. Mucosal Immunol 10:1190-1201

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