C. ABSTRACT OF PLANNED BODY OF WORK We plan to continue our studies of angiogenesis and remodeling in eosinophil associated diseases. Areas of innovation: The studies investigate novel pathways that are unexplored in mediating allergen induced remodeling (including Del-1 interacting with VEGF;MMP-7;trafficking of endothelial and fibroblast progenitors), use novel reagents (endothelial cell specific knockout of Del-1;Tie GFP and Col-1 GFP transgenic mice to track endothelial and fibroblast progenitors), and discovery approaches (proteomics, microarray) to identify differentially expressed genes/proteins in chronic vs acute allergen challenged lung (identified several candidates including Wnt signaling member Kremin;miRNA376b). In addition the availability of specimens from asthma and EE allow the findings to be translated to human subjects with remodeling.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AI038425-18
Application #
8597324
Study Section
Special Emphasis Panel (NSS)
Program Officer
Plaut, Marshall
Project Start
1996-04-01
Project End
2016-11-30
Budget Start
2013-12-01
Budget End
2014-11-30
Support Year
18
Fiscal Year
2014
Total Cost
$362,142
Indirect Cost
$128,502
Name
University of California San Diego
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Doherty, Taylor A; Broide, David H (2017) Pathways to limit group 2 innate lymphoid cell activation. J Allergy Clin Immunol 139:1465-1467
Chen, Jun; Miller, Marina; Unno, Hirotoshi et al. (2017) Orosomucoid-like 3 (ORMDL3) upregulates airway smooth muscle proliferation, contraction, and Ca2+ oscillations in asthma. J Allergy Clin Immunol :
Lund, Sean J; Portillo, Alex; Cavagnero, Kellen et al. (2017) Leukotriene C4 Potentiates IL-33-Induced Group 2 Innate Lymphoid Cell Activation and Lung Inflammation. J Immunol 199:1096-1104
Song, Dae Jin; Miller, Marina; Beppu, Andrew et al. (2017) Rhinovirus Infection of ORMDL3 Transgenic Mice Is Associated with Reduced Rhinovirus Viral Load and Airway Inflammation. J Immunol 199:2215-2224
Miller, Marina; Tam, Arvin B; Mueller, James L et al. (2017) Cutting Edge: Targeting Epithelial ORMDL3 Increases, Rather than Reduces, Airway Responsiveness and Is Associated with Increased Sphingosine-1-Phosphate. J Immunol 198:3017-3022
Eastman, Jacqueline J; Cavagnero, Kellen J; Deconde, Adam S et al. (2017) Group 2 innate lymphoid cells are recruited to the nasal mucosa in patients with aspirin-exacerbated respiratory disease. J Allergy Clin Immunol 140:101-108.e3
Miller, Marina; Rosenthal, Peter; Beppu, Andrew et al. (2017) Oroscomucoid like protein 3 (ORMDL3) transgenic mice have reduced levels of sphingolipids including sphingosine-1-phosphate and ceramide. J Allergy Clin Immunol 139:1373-1376.e4
Kim, Alexander S; Doherty, Taylor A; Karta, Maya R et al. (2016) Regulatory B cells and T follicular helper cells are reduced in allergic rhinitis. J Allergy Clin Immunol 138:1192-1195.e5
Miller, Marina; Esnault, Stephane; Kurten, Richard C et al. (2016) Segmental allergen challenge increases levels of airway follistatin-like 1 in patients with asthma. J Allergy Clin Immunol 138:596-599.e4
Das, Sudipta; Miller, Marina; Beppu, Andrew K et al. (2016) GSDMB induces an asthma phenotype characterized by increased airway responsiveness and remodeling without lung inflammation. Proc Natl Acad Sci U S A 113:13132-13137

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