Gregory Fleming James Cystic Fibrosis Research Center (CFRC) (University-Wide Interdisciplinary Research Center)

Director:  Eric J. Sorscher, MD

Established:  1981

 

Mission and Demographics

The Gregory Fleming James Cystic Fibrosis Research Center (CFRC) strives for an improved understanding of Cystic Fibrosis (CF) and related diseases, discovery of new CF treatments, and translation of fundamental laboratory research into clinical trials.  The Center currently has 61 active affiliated faculty representing 24 Departments and 10 Schools at UAB.

Center Research

            The Center’s major areas of basic research include electrophysiology, epithelial cell biology, pulmonary physiology and pathophysiology, gene transfer, and drug discovery.  Clinical research is focused primarily on drug intervention trials and studies of disease mechanism in CF patients. 

Examples of the CFRC’s emerging role in integrating research and service include the following:

·         UAB wrote the first protocol in the United States to investigate lipid-mediated gene transfer of wild-type CFTR to upper (nasal) airways in vivo.  The protocol received favorable comments from the NIH RAC and the FDA, was the first human gene transfer type protocol approved at UAB, and the first gene transfer experiment conducted at the Institution.

·         The Center completed the first FDA-approved trial in the United States to test lower (pulmonary) airway CFTR gene transfer of lipid/DNA complexes.  This study described a new clinical syndrome attributable to lipid/DNA, with relevance to other applications of gene transfer, including vaccines in diseases such as HIV, mycoplasma, influenza, and melanoma.  In addition, the results established successful gene transfer to the lower airways. 

·         Dr. David M. Bedwell (Microbiology) discovered that CFTR containing premature truncation mutations can be activated by administration of certain small molecules.  The CF Center has contributed to clinical trials indicating partial correction of Cl- transport defects in CF patients using this strategy and will provide further clinical leadership in this area in the future. 

·         The UAB cardiothoracic surgery service performed the first CF lung transplant in this part of the country, and now has become a leading referral center for the procedure. 

·         Weight loss is one of the strongest (negative) prognostic indicators in CF.  UAB investigators completed a study to show that Megestrol acetate leads to pronounced weight gain and improved lung function in CF patients with pancreatic insufficiency and malabsorption.  The results of this clinical trial were published with an accompanying editorial highlighting the findings by UAB investigators.

·         Dr. Raymond Lyrene (Pediatrics) completed the UAB component of a multicenter trial of azithromycin in CF therapy.  This drug has shown substantial promise as a mechanism for killing stationary phase Pseudomonas, and also appears to confer the benefit of other phenotypic improvements in CF airways.  UAB was one of the first sites to complete enrollment in the randomized, placebo-controlled, double-blinded trial of azithromycin in CF. 

·         Dr. J. P. Clancy (Pediatrics) has identified novel activators of A455E, G551D, R117H, and other partial function CFTR alleles.  These experiments indicate that compounds such as adenosine stimulate mutant CFTR through a pathway that requires both cAMP and PLA2.  In vitro observations and subsequent experiments in CF mouse models led to a clinical trial at UAB indicating that adenosine could serve as a general mechanism for activating CFTR in vivo. 

·         Dr. Kevin Kirk (Physiology and Biophysics) has identified new activators of mutant CFTR (including the most common disease-associated mutation).  The compound will be tested as a way to improve chloride secretion in the disease, and is expected to improve our understanding of mechanisms underlying cystic fibrosis ion channel dysfunction.

Background Concerning the UAB Cystic Fibrosis Research Center

The CFRC at UAB was the first in the nation to receive Research Development Program (RDP) support from the National CF Foundation and has served as a respected Center in studies designed to understand and treat CF.  UAB scientists published more than 90 manuscripts relevant to CF in peer-reviewed journals in 2001-2007.  These included important findings in journals such as NEJM, PNAS, Journal of Biological Chemistry, JCI, and Journal of Pediatrics. 

            A number of multi-investigator grants support Center activities, including Cores and Pilot Projects.  One of these, a SCOR award (NIH-NIDDK P50 DK53090, Molecular Aspects of CFTR Cellular Biology) began in 1997 and was designed to characterize the fundamental aspects of CFTR activity.  The CFRC also serves as the site for a CF Foundation Research Development Program grant.  The CF Center was awarded a multi-investigator grant to support translational research efforts as part of a National Therapeutic Development Network consortium (PIs: Clancy and Young).  A multi-investigator award also funds clinical development, and reinforces the basic and translational aspects of CF research on our campus (Pediatric Pulmonary Center, Maternal and Child Health Bureau).  In 2007 UAB was awarded an NIH P30 grant to serve as a Center for Cystic Fibrosis Clinical and Translational Research.

Core Facilities

            The UAB CFRC operates a number of scientific Core Facilities through its NIH and CF Foundation financial base support.  These Cores provide internationally respected expertise in CF electrophysiology, cell biology, and translational aspects of the disease.  Expertise includes: 1) CFTR ion transport, 2) CFTR expression in heterologous systems, 3) CF animal models, and 4) clinical and translational research.  These Cores are utilized by faculty at UAB and throughout the United States.

Training

The Center is very involved in training activities.  These include the basic and clinical training of graduate students and postdoctoral fellows in human genetics, physiology and biophysics, cell biology, and microbiology.  Training programs are funded through the CF Foundation and the NIH.

Leadership Activities of the Director 

Dr. Sorscher presented the opening plenary session talk at the North American CF meetings in 2002.  He served on the planning committee for the North American meetings, and as a co-chairman for the national meetings in 2003.  He helps oversee planning for the International CF meeting held annually in Williamsburg, VA.  He currently serves as chair of the “New Therapies” subcommittee for the North American Cystic Fibrosis Meetings and co-chair of an international CFTR protein folding consortium.

For additional information:

Business Officer:  Diane Taylor Baer

Email:  dtaylor@uab.edu

Phone:  205-934-7210

 

Approved by:  Eric J. Sorscher, MD, Director

Date:  April 4, 2008

 

 

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