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The CFTR Functional Analysis Core

Director: Martina Gentzsch, Ph.D.

Multiple research strategies for treatment of cystic fibrosis (CF) are currently being explored. Translating CF therapeutic strategies from basic research to clinical studies requires the assessment of drug candidates in physiologically relevant assays. To support translational CF research, the CFTR Functional Analysis Core pursues four objectives:

Ussing Chamber System

Ussing Chamber Systems for measuring electrophysiological characteristics of tissue samples and cell cultures.

1) Analyze ion channel properties and correction efficiency of human bronchial epithelial (HBE) cells from harvested CF lungs to provide a full characterization report to investigators.

2) Measure ion transport function of CFTR and ENaC in HBE and human nasal epithelial (HNE) cultures by bioelectric and organoid assays to asses efficacy of candidate therapies.

3) Evaluate CFTR expression and processing by biochemical analyses to assess efficacy of CFTR modulation strategies.

4) Validate the suitability of reagents, supplies, and techniques for optimizing HBE and HNE cell integrity.

Although numerous investigators using services provided by the CFTR Functional Analysis Core focus on restoration of CFTR function in CF cells by small-molecule pharmacological interventions, our services offer broad applications to multiple research programs that examine gene targeting/therapy, modifier genes, and impact of environmental factors such as inflammation, infection, and smoking on epithelial ion transport. Furthermore, our services allow for the correlation of CFTR activity with other outcome measures such as airway surface liquid hydration and mucus clearance.

Rescue of DF508 and G551D in CF HBE cells.
Rescue of DF508 and G551D in CF HBE cells. ∆F508/∆F508 (A-C) or G551D/∆F508 (D-G) CF HBE cells were treated chronically with VX-809 or VX-770 for 48 hrs (cV809, cVX770). A, D. CFTR function was then characterized in HKLC/KBR in Ussing chambers. Amil=amiloride, Fsk=forskolin, CFTRinh172. ∆F508/∆F508 cells from 5 patients and G551D/∆F508 cells from 3 patients were analyzed (N=3-4). B, E. Chronic treatment with VX-809 and VX-770 restores CFTR function in ∆F508/∆F508 and G551D/∆F508 cultures, respectively. C, G. CFTR in cell lysates was analyzed by Western blotting. VX809 treatment leads to formation of band C (*) in ∆F508/∆F508 cells. F. Acute and chronic VX770 treatments have similar outcomes in G551D/∆F508 cells.

Core Personnel:

Martina Gentzsch, Ph.D.
Deborah Cholon, Ph.D.
Nancy Quinney (Research Specialist)
Susan Boyles (Research Specialist)
 

Acknowledgement:

This Core is part of a CFF-supported Research Development Program (BOUCHE19R0).
 

Contact Information

Martina Gentzsch, Ph.D.
Assistant Professor, Department of Cell Biology and Physiology
Director, Pre-Clinical Core
Director, CFTR Functional Analysis Core
Marsico Lung Institute/Cystic Fibrosis Research Center
The University of North Carolina
1121 Marsico Hall CB 7248
125 Mason Farm Road
Chapel Hill, NC 27599

Phone:(919) 966-7058
Fax:(919)966-5178
E-mail: gentzsch@med.unc.edu