Biomedical Research Funded in 1997

CFRI News, Spring 1998

Editor's Note: CFRI funds cystic fibrosis research in two cycles every year. Last year the following researchers and their proposals were recommended for funding by the Research Advisory Committee and approved by the Board of Directors and General Membership of CFRI. The total funds awarded for 1997 amounted to $263,004.

Spring Cycle:

"CFTR Regulates Fusion of Exocytic Vesicles Containing CFTR"
Principal Investigator: Horst Fischer, Ph.D., Children's Hospital, Oakland, CA
Amount funded: $25,000
This proposal investigates the initial step of CFTR delivery to the plasma membrane. Dr. Fischer will test the hypothesis that CFTR mutations also affect exocytic vesicle delivery. This is solid basic research on chloride (Cl) channel fusion with the specific aim to 1) establish a method to measure cell membrane capacitance in cells and epithelia and 2) to understand the role of CFTR to vesicle fusion. The hope is that this proposal will result in new insights into the mechanisms of the defective regulation of Cl secretion in CF by examining the effects of CFTR on membrane delivery.

"Small Fragment Homologous Replacement (SFHR) of Genomic CFTR in Vivo"
Principal Investigator: Dieter Gruenert, Ph.D., University of California at San Francisco, CA
Amount funded: $40,000
The prospect of directly correcting the mutant portion of disease-causing genes is one of the main goals of gene therapy. SFHR is an alternative to classic gene therapy approaches that use adenoviral vectors and transfer of CFTR-DNA by liposomes. SFHR uses small fragments of DNA to replace CFTR sequences. This approach has been successful in airway epithelial cells, and other cell lines, including a nasal polyp cell line. Dr. Gruenert will now test this process in vivo. (Note: Dr. Gruenert's work is featured in the lead research article of this issue of CFRI News)

"Cellular Mechanisms Possibly Leading to Obliterative Bronchiolitis"
Principal Investigators: Randall Morris, M.D., and Amrita Dosanjh, M.D., Stanford University Medical Center, Stanford, CA
Amount funded: $30,000
CF patients represent the largest patient population awaiting bilateral or heart-lung transplants. Obliterative bronchiolitis (OB) is the major cause of morbidity and mortality among CF transplant recipients. RapamycinT is a new Wyeth drug with the potential for being an effective immunosuppressant agent. This is a new cell culture study to determine the effect of Rapamycin on dangerous fibroblast growth related to OB.

"Establishing Surrogate Markers for Gene Therapy: Efficacy of AAV-CFTR Vectors"
Principal Investigators: Phyllis Gardner, M.D. and Carol Conrad, M.D., Lucile Packard Children's Hospital, Stanford University, Stanford, CA
Amount funded: $24,000
CF patients have abnormal salt secretions because the protein that usually does the job of salt regulation is abnormally formed. The goal of gene therapy is to add a normal copy of the DNA needed for normal protein. AAV has been shown to be a safe and possibly effective gene delivery vehicle. The objectives of this study are to detect the presence of protein at the proper place in the cells of the patients' airways and whether there are other protein markers. AAV-CFTR vector research is occurring at Hopkins, Florida and at Stanford. Phase 1 patient clinical trials have been conducted at Stanford. This study seeks to develop surrogate markers for biological efficacy of AAV-CFTR vectors being used in clinical trials.

"Electron Beam-Computed Tomography (EBCT)"
Principal Investigators: Richard Moss, M.D., Director, Cystic Fibrosis Clinic, and Terry Robinson, M.D., Lucile Packard Children's Hospital at Stanford University, Stanford, CA
Amount funded: $15,000 (extension of funds for a project begun in late 1996)
This research is a continuation of a study funded by CFRI in 1996 to develop a new CF lung disease scoring system using electron beam CT scanning, called Electron Beam-Computed Tomography (EBCT). EBCT imaging of the chest shows considerable promise for delineating early changes (damage) in the CF airway and the ability to assess the spectrum of CF pulmonary disease.

Chori Fellowship
Amount Funded: $5,004
Stipends for two undergraduate students working in the the CF Lab at Oakland Children's Hospital, Oakland,CA for a period of one year.

Fall Cycle:

"Culture of Tracheobronchial Serous Gland Cells"
Principal Investigator: Walt Finkbeiner, M.D., Ph.D., University of California at San Francisco
Amount Funded: $24,000
Dr. Finkbeiner is developing a system that promotes growth and differentiation of the tracheobronchial serous gland phenotype in culture. Serous gland cells are the main CFTR-bearing cells in the lung. It is hoped that these cells could be used as an experimental system for drug and gene therapy trials.

"High-Resolution CT Imaging in Mild Cystic Fibrosis Pulmonary Disease Using Electron Beam-Computed Tomography"
Principal Investigators: Richard Moss, M.D., Director of the Cystic Fibrosis Clinic, and Terry Robinson, M.D., Lucile Packard Children's Hospital at Stanford Hospital, Stanford, CA
Amount funded: $36,000 (extension of funds)
This research is a continuation of a study funded by CFRI in 1996 to develop a new CF lung disease scoring system using electron beam CT scanning.

"Nasal Potential Difference Measurements for Genotype/Phenotype Correlation and Outcome of Aminoglycoside Therapy in CF"
Principal Investigator: Mark Weatherly, M.D., Emory University Medical Center, Atlanta, GA
Amount funded: $34,000
The aim of this study is to confirm whether the 2% to 10% of CF individuals with stop mutations can maintain functional CFTR in the airway epithelial cells via chronic Gentamicin therapy.

$6,000 one-time awards
were given to the following laboratories with the stipulation that it be used directly for cystic fibrosis research.
Total amount of awards: $30,000

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