Numerous investigators within the current P30 application have indicated a need for 1) primary human airway epithelial cells (from lung transplantation) or nasal epithelial cells from CF and non-CF individuals;2) measurements of the functional anatomy of respiratory epithelia that track airway surface liquid homeostasis, ciliary beating, and mucociliary transport;or 3) CFTR bioelectric assays in human subjects. Core C is intended to provide the necessary expertise and supply these reagents in a centralized, standard format. The Core will facilitate transition from in vitro proof of concept studies to in vivo analysis, and furnish expertise in cell culture, airway physiology, and human translational science.
The specific aims of Core C are:
Specific Aim 1 : To procure, grow, and distribute well-differentiated primary human airway epithelial cells from CF and non-CF donors. The Core will interface with human subjects to (1) procure, derive, and grow cells from lung transplants, nasal polypectomies, or nasal brushings;(2) maintain a robust informatics system that includes clinical information regarding consenting subjects, CFTR genotyping, performance of cells in culture, and a large repository of frozen cells for the P30 Center;and (3) provide quality assurance and regulatory expertise necessary to protect the rights and safety of human subjects, including IRB submissions, material transfer agreements, and HIPAA compliance.
Specific Aim 2 : To conduct functional anatomic imaging of airway epithelia by 1-micron resolution Spectral Domain-Optical Coherence Tomography (?mu?OCT) in vitro and ex vivo. The Core will conduct ?mu?OCT imaging of the functional anatomy of respiratory epithelia in (1) fully-differentiated primary epithelial cells (of human or non-human origin);and (2) intact full-thickness tracheas from animal (e.g. pig, ferret, rat) or human origin.
Specific Aim 3 : To support the design and conduct in vivo measurements of CFTR activity in human subjects. The Core will provide expertise in the conduct of NPD measurements, assist in the development of new in vivo assays of CFTR activity (e.g intestinal current measurements), and provide data management, biostatistical, and regulatory expertise to assist in the design, conduct, and interpretation of CF clinical trials utilizing these in vivo capabilities. As such, Core C is poised to """"""""bridge the gap"""""""" between in vitro proof of concept studies, new clinical insight regarding disease mechanisms, and clinical translation of novel CF therapeutics.
(See Instructions):
| Shei, Ren-Jay; Peabody, Jacelyn E; Kaza, Niroop et al. (2018) The epithelial sodium channel (ENaC) as a therapeutic target for cystic fibrosis. Curr Opin Pharmacol 43:152-165 |
| Gebert, Magdalena; Bartoszewska, Sylwia; Janaszak-Jasiecka, Anna et al. (2018) PIWI proteins contribute to apoptosis during the UPR in human airway epithelial cells. Sci Rep 8:16431 |
| Montoro, Daniel T; Haber, Adam L; Biton, Moshe et al. (2018) A revised airway epithelial hierarchy includes CFTR-expressing ionocytes. Nature 560:319-324 |
| Lutful Kabir, Farruk; Ambalavanan, Namasivayam; Liu, Gang et al. (2018) MicroRNA-145 Antagonism Reverses TGF-? Inhibition of F508del CFTR Correction in Airway Epithelia. Am J Respir Crit Care Med 197:632-643 |
| Shei, Ren-Jay; Peabody, Jacelyn E; Rowe, Steven M (2018) Functional Anatomic Imaging of the Airway Surface. Ann Am Thorac Soc 15:S177-S183 |
| Clancy, John Paul; Cotton, Calvin U; Donaldson, Scott H et al. (2018) CFTR modulator theratyping: Current status, gaps and future directions. J Cyst Fibros : |
| Plyler, Z E; Birket, S E; Schultz, B D et al. (2018) Non-obstructive vas deferens and epididymis loss in cystic fibrosis rats. Mech Dev : |
| Poore, T Spencer; Virella-Lowell, Isabel; Guimbellot, Jennifer S (2018) Potential pathogenicity of Inquilinus limosus in a pediatric patient with cystic fibrosis. Pediatr Pulmonol 53:E21-E23 |
| Heltshe, Sonya L; Rowe, Steven M; Skalland, Michelle et al. (2018) Ivacaftor-treated Patients with Cystic Fibrosis Derive Long-Term Benefit Despite No Short-Term Clinical Improvement. Am J Respir Crit Care Med 197:1483-1486 |
| Guimbellot, Jennifer; Solomon, George M; Baines, Arthur et al. (2018) Effectiveness of ivacaftor in cystic fibrosis patients with non-G551D gating mutations. J Cyst Fibros : |
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