Abstract

The focus of this proposal is on ORMDL-3, a protein localized to chromosome 17q21, which has been highly linked to asthma in several genome wide association studies.
The aim of this project is on understanding how ORMDL3 expressed in bronchial smooth muscle cells influences smooth muscle contraction through activation of SERCA2b. The study will utilize human lung smooth muscle cells in vitro, human lung sections of asthmatics ex vivo, and in vivo studies examining mice expressing the human ORMDL3 transgene in smooth muscle to determine how ORMDL3 activates SERCA2b to regulate smooth muscle phenotypic changes and contraction in vitro, and influences levels of smooth muscle and airway hyperreactivity in vivo. Overall, these studies will provide important insight into how ORMDL3, a gene highly linked to asthma, contributes to smooth muscle remodeling and asthma.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
2U19AI070535-11
Application #
9154624
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2016-09-01
Budget End
2017-08-31
Support Year
11
Fiscal Year
2016
Total Cost
Indirect Cost

  Institution

Name
University of California San Diego
Department
Type
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093

  Publications

Karta, Maya R; Rosenthal, Peter S; Beppu, Andrew et al. (2018) ?2 integrins rather than ?1 integrins mediate Alternaria-induced group 2 innate lymphoid cell trafficking to the lung. J Allergy Clin Immunol 141:329-338.e12
Mehta, A K; Doherty, T; Broide, D et al. (2018) Tumor necrosis factor family member LIGHT acts with IL-1? and TGF-? to promote airway remodeling during rhinovirus infection. Allergy 73:1415-1424
Doherty, Taylor A; Broide, David H (2018) Lipid regulation of group 2 innate lymphoid cell function: Moving beyond epithelial cytokines. J Allergy Clin Immunol 141:1587-1589
da Silva Antunes, Ricardo; Mehta, Amit K; Madge, Lisa et al. (2018) TNFSF14 (LIGHT) Exhibits Inflammatory Activities in Lung Fibroblasts Complementary to IL-13 and TGF-?. Front Immunol 9:576
Unno, Hirotoshi; Miller, Marina; Rosenthal, Peter et al. (2018) Activating transcription factor 6? (ATF6?) regulates airway hyperreactivity, smooth muscle proliferation, and contractility. J Allergy Clin Immunol 141:439-442.e4
Miller, Marina; Vuong, Christine; Garcia, Meghan Farrell et al. (2018) Does reduced zona pellucida binding protein 2 (ZPBP2) expression on chromosome 17q21 protect against asthma? J Allergy Clin Immunol 142:706-709.e4
Ordovas-Montanes, Jose; Dwyer, Daniel F; Nyquist, Sarah K et al. (2018) Allergic inflammatory memory in human respiratory epithelial progenitor cells. Nature 560:649-654
Herro, Rana; Shui, Jr-Wen; Zahner, Sonja et al. (2018) LIGHT-HVEM signaling in keratinocytes controls development of dermatitis. J Exp Med 215:415-422
Chen, Jun; Miller, Marina; Unno, Hirotoshi et al. (2018) Orosomucoid-like 3 (ORMDL3) upregulates airway smooth muscle proliferation, contraction, and Ca2+ oscillations in asthma. J Allergy Clin Immunol 142:207-218.e6
White, Andrew A; Doherty, Taylor A (2018) Role of group 2 innate lymphocytes in aspirin-exacerbated respiratory disease pathogenesis. Am J Rhinol Allergy 32:7-11

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