Translational Studies

Mucoiliary Clearance
(Nuclear Imaging of mucociliary clearance in lungs before treatment with ivacaftor (A-C) and after treatment (D-F)

The Translational Studies Core will provide the infrastructure for new pre-clinical studies and clinical trials to investigate pathogenesis and evaluate new pharmacological or genetic therapies to treat Cystic Fibrosis by providing access to over 500 patients followed by the CF Center.  The Core’s mission is to support and maintain an analytical lab, which supports state-of-the-art measurements of inflammatory mediators and gene expression, to perform physiological outcome measures and provide statistical support, and to manage a sample repository. 

Goal: Facilitate the clinical research activities of Center investigators and collaborators

Our four objectives:

Perform specialized analytical assays and provide expertise in animal models to facilitate translational CF research
Specialized assays include a) multi-plex based assays for cytokines and chemokines, b) quantitative and functional myeloperoxidase and neutrophils elastase measurements, and c) qPCR and RNAseq analysis of clinical samples.  These assays are currently being used by Center investigators to examine the mechanisms which promote airway inflammation in CF, specifically the roles of Interleukins-17, -22, and -23, and to assess the ability of a novel epigenetic modulator to modify lymphocyte responses to CF pathogens.  Additionally, the Core will provide expertise in the use of animal models to study pathogenesis of inflammation and infection in CF.

Provide the infrastructure to perform physiological measures as endpoints in clinical trials, and to execute early Phase studies of novel therapies
Our translational core has extensive expertise with the development and execution of multiple clinical endpoint measures.  The Translational Core will continue to facilitate a) in vivo airway absorptive/mucociliary clearance scans; b) nasal potential difference (NPD) measurement, and c) lung clearance index (LCI) measurement.  Specific studies that are currently supported by the Core will complete validation of the novel absorptive/mucociliary clearance scans as an outcome measure, and to determine whether inhaled bicarbonate is an effective alternative to hypertonic saline as a CF therapy.

Provide infrastructure in biostatistics to support the development of novel investigator-initiated research in CF
The biostatistics component of the Core will provide assistance in the statistical aspects of the design and data analysis of studies conducted at the Cystic Fibrosis Research Center.  Examples include power analyses for Phase I/II clinical studies, and mathematical modeling of absorptive/mucociliary clearance scans. 

Maintain and expand a sample bank of serum, sputum, and epithelial cells from CF patients participating in investigator-initiated research and from a longitudinal biomarkers study
Samples of sputum, serum, bronchoalveolar lavage, and airway/nasal epithelial cells will be processed and stored with accompanying clinical information.  These samples will be used to support exploratory studies and inform future studies.

In addition to the four Specific Objectives, the Core will continue to support Center investigator studies that aim to develop novel therapies for the life-shortening lung disease in CF.  These studies include evaluating RNAseq on epithelial cells from upper and lower airways in CF, and designing and executing Phase I/II studies of inhaled sodium nitrite as an antibacterial agent in patients with CF.  In addition to these aims, the personnel in this Core will train other personnel and will help coordinate research efforts among projects.