History: The Cystic Fibrosis Foundation established a Research Development Program Center for research in cystic fibrosis with a five-year, $2 million grant in 1997.  It was renewed in 2002 and 2007.  The primary goal of the Center is to focus the attention of new and established investigators on multidisciplinary approaches designed to improve the understanding and treatment of cystic fibrosis (CF).  In creating this Center, the CF Foundation took advantage of unique opportunities present at the School of Medicine and the Children’s Hospital at the University of Pittsburgh, including a large and accessible patient population for pre-clinical and clinical research and excellent availability of patient lung tissue due to a large volume of transplant activity.  The Center provides the opportunity to engage excellent investigators in CF research in an institution that ranks 7th nationally in extra-mural support by the NIH.  The University of Pittsburgh RDP Center is one of nine such Centers supported by the CF Foundation in North America. 

Funding: In addition to the RDP award, the Center was the recipient, in 2004, of a Core Center grant in CF from the NIH (P30 entitled, “Basic and Clinical Studies of Cystic Fibrosis”).  Two such Centers were awarded nationally.   The CF Research Center is directed by Raymond A. Frizzell, Ph.D., with extensive interactions with clinical colleagues and co-Directors, Drs. Joseph Pilewski and Jay Kolls.  The NIH Center supports pilot research projects and core facilities.  The P30 award criterion was a research base of existing R01 grants awarded to Center investigators, which its Cores would support and extend. The current Center is housed in the Department of Cell Biology and Physiology, 3rd floor BST South, in the Adult Pulmonary Division of the Department of Medicine, 6th floor MUH, and in the Pediatric Pulmonary Division at the Children’s Hospital of Pittsburgh.

Research: The Center’s research efforts focus on several areas relevant to the understanding and treatment of CF: basic studies of the function, protein interactions, trafficking and processing of the CF gene product, CFTR; understanding the infection-inflammation issues that compromise the function of CF airways; the development of new therapies and diagnostic approaches for treating CF, and participation of Center investigators in clinical studies.  Our funding mechanisms allow the Center to encourage interactions between investigators with long-standing interests and accomplishments in CF research and to bring new investigators into the CF field.

Research and Clinical Cores:

Molecular Biology/Gene Expression:  The purpose of this core is to provide access to molecular reagents and techniques, to provide systems for gene expression, and standardized quality control.  This core provides constructs for expression of CFTR, the amiloride-sensitive Na channel, ENaC, and various regulatory reagents and enzymes.  It interfaces with facilities for functional assays and protein expression.  [Core Director: Fei Sun, Ph.D., Cell Biology and Physiology]

Cell and Tissue Imaging Core:  This core is housed within the Center for Biologic Imaging of the Department of Cell Biology and Physiology.  It provides investigators within the RDP with access to state-of-the-art imaging techniques.  Its primary focus is immunocytochemistry; however, the core has been involved in the development of new methods for measurements of ciliary beat frequency, ciliary clearance and water permeability.  [Core Director: Simon Watkins, Ph.D., Cell Biology and Physiology]

Assay Core:  The purpose of this core is to provide functional assays for CFTR and other proteins.  Its menu includes fluorescence assays for anion permeability, transepithelial current, conductance, impedance and current fluctuation analysis in polarized airway or intestinal cell cultures, both established cell lines and primary culture obtained from the Human Airway Cell Core (below).  Facilities and personnel for performing whole-cell and single channel patch clamp measurements are also available. [Core Director: Carol Bertrand, Ph.D., Cell Biology and Physiology]

Human Airway Cells:  This core provides access to patient materials obtained as a result of lung transplant activities in the Department of Surgery.  This core offers procedures for cultured human airway epithelia, organotypic cultures and human airway cell xenografts, to facilitate a variety of pre-clinical investigations.  [Core Director: Joseph Pilewski, M.D., Department of Medicine, Division of Pulmonary and Critical Care Medicine]

Clinical Studies:  This core provides facilities and personnel for implementing clinical trials.  It provides procedures for identifying functional outcomes, monitored in terms of lung function, ion transport, inflammatory mediator levels or gene expression.  It maintains patient records and procedures for enrolling patients in clinical studies.  [Core Directors: Joseph Pilewski, M.D., and Jay Kolls, M.D., Departments of Medicine and Pediatrics]