Core B, that was favorably received and budget approved, will provide all human airway smooth muscle (HASM) cell lines, precision cut lung slice (PCLS) studies and magnetic twisting cytometry (MTC) measurements of single ASM force generation that will be used in the research projects. Our laboratory has 20 years of experience in the establishment, cultivation and characterization of HASM cells. Core B will provide and develop novel platforms to measure bronchoconstriction and bronchodilation in HASM cells using MTC and in human small ainways using human PCLS (hPCLS) to characterize E-C signal transduction processes. Quality assurance and characterization of cell lines will be performed using our established approaches. The use of ASM cell lines derived coincident with hPCLS provides a unique cell- and tissue- based platform that enables investigators to molecular dissect the contribution of specific cell signaling events in the regulation of physiologically relevant ex vivo outcomes.
The aims of this facility core will meet the anticipated needs ofthe four interactive projects. In Project 1, PCLS will sen/e as a useful model in the characterization of p^-adrenergic receptor (PjAR) desensitization in HASM cells from non-asthma and fatal asthma subjects and will provide an opportunity to moleculariy dissect critical signaling pathways by which steroids modulate p^AR tachyphylaxis. In Project 2, HASM cells will be used to characterize taste receptor- mediated inhibition of ASM contraction and desensitization regarding the taste receptor ligands. In Project 3, HASM cell lines and hPCLS will be used to determine the role of proton-activated GPCR regulation ofthe contractile responses as measured by twisting cell microscopy or calcium mobilization studies performed in HASM cells and by bronchoconstriction in PCLS. In Project 4, HASM cell lines and hPCLS will be used to define novel approaches to inhibit p^AR desensitization and G^-mediated contractile responses. A centralized human cell and tissue core with faculty and research staff adept in the manipulation of HASM cells is a unique asset that ensures success and provides advantages with regard to centralized quality assurance across the Program Project grant.

Public Health Relevance

Core B will provide human cells and tissue for the Program Project Grant in order to characterize molecular mechanisms regulating bronchoconstriction and bronchodilation.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
Project #
Application #
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Pennsylvania
United States
Zip Code
Aisenberg, William H; Huang, Jessie; Zhu, Wanqu et al. (2016) Defining an olfactory receptor function in airway smooth muscle cells. Sci Rep 6:38231
Carr 3rd, Richard; Schilling, Justin; Song, Jianliang et al. (2016) β-arrestin-biased signaling through the β2-adrenergic receptor promotes cardiomyocyte contraction. Proc Natl Acad Sci U S A 113:E4107-16
Carr 3rd, Richard; Koziol-White, Cynthia; Zhang, Jie et al. (2016) Interdicting Gq Activation in Airway Disease by Receptor-Dependent and Receptor-Independent Mechanisms. Mol Pharmacol 89:94-104
Ghosh, Arnab; Koziol-White, Cynthia J; Asosingh, Kewal et al. (2016) Soluble guanylate cyclase as an alternative target for bronchodilator therapy in asthma. Proc Natl Acad Sci U S A 113:E2355-62
Xie, Yan; Jiang, Haihong; Zhang, Qian et al. (2016) Upregulation of RGS2: a new mechanism for pirfenidone amelioration of pulmonary fibrosis. Respir Res 17:103
Pera, Tonio; Penn, Raymond B (2016) Bronchoprotection and bronchorelaxation in asthma: New targets, and new ways to target the old ones. Pharmacol Ther 164:82-96
Dileepan, Mythili; Sarver, Anne E; Rao, Savita P et al. (2016) MicroRNA Mediated Chemokine Responses in Human Airway Smooth Muscle Cells. PLoS One 11:e0150842
Kim, Donghwa; Pauer, Susan H; Yong, Hwan M et al. (2016) β2-Adrenergic Receptors Chaperone Trapped Bitter Taste Receptor 14 to the Cell Surface as a Heterodimer and Exert Unidirectional Desensitization of Taste Receptor Function. J Biol Chem 291:17616-28
An, Steven S; Mitzner, Wayne; Tang, Wan-Yee et al. (2016) An inflammation-independent contraction mechanophenotype of airway smooth muscle in asthma. J Allergy Clin Immunol 138:294-297.e4
Billington, Charlotte K; Penn, Raymond B; Hall, Ian P (2016) β2 Agonists. Handb Exp Pharmacol :

Showing the most recent 10 out of 38 publications