# Core B: Molecular/Functional Measurement Core

> **NIH NIH P30** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $344,632

## Abstract

ABSTRACT
Cystic fibrosis (CF), the most common lethal genetic disease in the Caucasian population, results from mutations
in the CFTR gene and affects the epithelia of multiple organs including the lung and gastrointestinal tract. Multiple
research strategies for treatment of 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
that require specific expertise. To support urgently required translational CF research, the Molecular/Functional
Measurement Core (Core B) of the University of North Carolina CF Research and Translation Core Center will
pursue two Specific Aims: Specific Aim 1 will focus on in vitro evaluation of multi-organ CF disease
pathophysiology and pre-clinical therapeutics candidates. We will provide in vitro analyses of CF primary
cultured, stem-cell derived, and freshly biopsied epithelia (GI and airway) by Ussing chamber ion transport,
biochemical measurements, and molecular studies to quantitate CFTR expression/function/maturation, organoid
swelling assays to measure CFTR function in higher throughput assays, and novel models to study inflammation,
infection, hypoxia, and pharmacokinetics/pharmacodynamics analyses of designated CF therapeutic agents and
endpoints. Specific Aim 2 will provide in vivo evaluation of CF disease pathophysiology and therapeutic
candidates utilizing animal models. Animal models include CF mice and CF rabbits, β-ENaC overexpressing
mice, secreted and tethered mucin-deficient mice, and gnotobiotic mice. We will provide mouse model
development, colony maintenance, and genotyping of mutant mice relevant to studies of CF GI and lung disease,
phenotyping of naïve and challenged animal models (mouse and rabbit) by validated GI and pulmonary
phenotyping panels, sample collection and preparation for microbiome analyses, histopathology,
immunostaining, RNAscope in situ hybridization, and q-PCR. Outcomes will include mucus burden and
clearance, infection/microbiome, inflammation, pharmacokinetics, gene expression, and ion channel-mediated
function (e.g., salivary secretion, nasal potential difference). Pharmacokinetics services are available for both
Aims by mass spectrometry. While certain assays and models provided by the Core focus on restoration of
CFTR function in CF, most of our services have broad applications to multiple research programs seeking
therapeutic benefit for CF. These services include approaches that utilize small-molecule pharmacological
interventions, gene therapy, correction of mucus defects, normalization of ion transport, and
inflammation/infection control. The availability of these models and assays will provide a translational bridge that
will support the rapid transfer of emerging drug candidates to effective therapies for CF patients.

## Key facts

- **NIH application ID:** 10227486
- **Project number:** 5P30DK065988-17
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Martina Gentzsch
- **Activity code:** P30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $344,632
- **Award type:** 5
- **Project period:** 2003-09-30 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10227486

## Citation

> US National Institutes of Health, RePORTER application 10227486, Core B: Molecular/Functional Measurement Core (5P30DK065988-17). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10227486. Licensed CC0.

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