Airway epithelial cells play a major role in asthma. We recently discovered striking abnormalities in epithelial expression of micro-RNAs (miRNAs) in most subjects with asthma. The overall goal of this project is to understand the nature, causes and consequences of altered epithelial miRNA expression in asthma. Our preliminary studies suggest that IL-13 is responsible for miRNA abnormalities seen in many asthmatics. IL- 17 also alters epithelial miRNA expression, a finding that may be especially relevant for individuals with severe asthma. Epithelial miRNA abnormalities were only modestly reversed by corticosteroid treatment, suggesting that miRNAs may represent novel therapeutic targets for steroid-resistant asthma. Some ofthe miRNAs that are changed in asthma are known to regulate mucociliary differentiation in related systems, but the functional consequences of altered epithelial miRNA expression in asthma remain to be determined. This project has 3 specific aims: 1) Identify epithelial miRNAs that are altered in severe asthma and relate their expression to IL-13 and IL-17 production and mucous metaplasia in the airway, 2) Determine how IL-13 and IL-17 affect miRNA levels in human bronchial epithelial (HBE) cells, and 3) Determine how selected IL-13- and IL-17-regulated miRNAs affect HBE cell gene expression, differentiation and function. These studies will impact asthma research by identifying novel pathophysiologic mechanisms, providing new tools for molecular phenotyping of asthma subsets, and discovering novel therapeutic targets.
Epithelial cells line the airways and play an important role in asthma. Micro-RNAs regulate gene expression. We will identify the nature, causes and consequences of changes in airway epithelial cell micro-RNAs in asthma.
|Bhakta, Nirav R; Christenson, Stephanie A; Nerella, Srilaxmi et al. (2018) IFN-stimulated Gene Expression, Type 2 Inflammation, and Endoplasmic Reticulum Stress in Asthma. Am J Respir Crit Care Med 197:313-324|
|Levin, Albert M; Gui, Hongsheng; Hernandez-Pacheco, Natalia et al. (2018) Integrative approach identifies corticosteroid response variant in diverse populations with asthma. J Allergy Clin Immunol :|
|Wong-McGrath, Kelly; Denlinger, Loren C; Bleecker, Eugene R et al. (2018) Internet-Based Monitoring in the Severe Asthma Research Program Identifies a Subgroup of Patients With Labile Asthma Control. Chest 153:378-386|
|Oh, Sam S; Du, Randal; Zeiger, Andrew M et al. (2017) Breastfeeding associated with higher lung function in African American youths with asthma. J Asthma 54:856-865|
|Sherenian, M G; Cho, S H; Levin, A et al. (2017) PAI-1 gain-of-function genotype, factors increasing PAI-1 levels, and airway obstruction: The GALA II Cohort. Clin Exp Allergy 47:1150-1158|
|Bonser, Luke R; Erle, David J (2017) Airway Mucus and Asthma: The Role of MUC5AC and MUC5B. J Clin Med 6:|
|Yi, L; Cheng, D; Zhang, K et al. (2017) Intelectin contributes to allergen-induced IL-25, IL-33, and TSLP expression and type 2 response in asthma and atopic dermatitis. Mucosal Immunol 10:1491-1503|
|Sundaram, Aparna; Chen, Chun; Khalifeh-Soltani, Amin et al. (2017) Targeting integrin ?5?1 ameliorates severe airway hyperresponsiveness in experimental asthma. J Clin Invest 127:365-374|
|Thakur, Neeta; Barcelo, Nicolas E; Borrell, Luisa N et al. (2017) Perceived Discrimination Associated With Asthma and Related Outcomes in Minority Youth: The GALA II and SAGE II Studies. Chest 151:804-812|
|Wells, Karen E; Cajigal, Sonia; Peterson, Edward L et al. (2016) Assessing differences in inhaled corticosteroid response by self-reported race-ethnicity and genetic ancestry among asthmatic subjects. J Allergy Clin Immunol 137:1364-1369.e2|
Showing the most recent 10 out of 117 publications