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.

Public Health Relevance

(See Instructions):

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Center Core Grants (P30)
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Special Emphasis Panel (ZDK1-GRB-7 (J1))
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University of Alabama Birmingham
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