Cystic Fibrosis Foundation Opens New Research Door with Proteomics at OHSU

04/12/02    BETHESDA, Maryland

Cystic Fibrosis Foundation Therapeutics, Inc., (CFFTI), the drug discovery and development arm of the Cystic Fibrosis Foundation, today announced that it has awarded $480,000 to scientists at Oregon Health & Science University (OHSU) to harness the power of cutting-edge proteomics to accelerate the search for new cystic fibrosis (CF) therapies.

CF researchers are poised to explore proteomics, an innovative area of biomedical science, to discover potential therapeutics for CF and to form new diagnostic tools. Genomics, the identification of all of the genes in an organism's DNA -- from bacteria to human beings -- has provided complete genetic maps. Most genes produce proteins that serve as the work-horses of the cell. Scientists are using proteomics technologies to identify all of the proteins in a cell or tissue, and to study their functions and the interactions among these proteins. Proteins direct cellular functions, and abnormal protein interactions have been associated with disease, including CF.

"By supporting proteomics, the CF Foundation opens a brand new door in our search for a cure or control for CF," said Robert J. Beall, Ph.D., president and chief executive officer of the CF Foundation. "We are particularly hopeful about the potential of proteomics because it offers the possibility of discovering drug targets that would correct the root cause of the disease."

Seeing the huge drug discovery potential of this field for CF research, the CF Foundation gave a proteomics research award to William R. Skach, M.D., associate professor of medicine in the division of molecular medicine, at OHSU's School of Medicine. Skach brings to this proteomics initiative his expertise regarding activities of the CF-associated protein, cystic fibrosis transmembrane conductance regulator (CFTR). The activities include when CFTR is made in the cell and folded into its functional shape.

Normally, this protein is found in cells that line certain organs, including the lungs and the pancreas. CFTR's function is to form a channel for the flow of chloride particles through the cell membrane. In CF, the protein fails to perform its job -- either not at all or insufficiently -- leading to an imbalance of salt and water at the inner lining of these organs. Abnormally thick, sticky mucus develops, causing the progressive respiratory and digestive problems that characterize CF.

Although most of the tools used in proteomics studies are not new, only recently has automation of many of these methods been possible, allowing for more rapid, continuous use. Recognizing this evolution in proteomics technology, the CF Foundation decided the time was right to make use of this powerful biomedical research strategy in CF.

"It has become clear in the last several years that the CFTR protein interacts with a large number of intercellular proteins, and we are just beginning to understand what those proteins might be and

how those interactions might be important in developing CF," said Skach. "Proteomics provides the ability to look at protein-protein interactions in a way that previously could not have been done."

Many proteins interact with the CFTR protein during all of its functions, including synthesis, folding, transportation to the cell membrane and degradation. In the OHSU study, scientists hope to identify proteins that have important interactions with CFTR during its early processing. They then will compare such interactions in mutant (disease-associated) versus normal CFTR. The ultimate goal is to find novel targets for new CF drugs. These targets could then be developed into high-throughput "screens," or tests, to facilitate the accelerated discovery of novel drugs. A CF therapy that can promote normal function of CFTR, in theory, could prevent the disease's progressive and fatal symptoms from developing.

"We are driven by the idea that if we can understand how certain proteins are working with CFTR, we can then identify key proteins that will be critical in its development, and ultimately identify small-molecular agents that can be used as drugs to influence those absolutely critical interactions," Skach explained. This approach also could prove useful in other diseases with abnormal protein processing, such as long Q-T syndrome (a cardiac arrhythmia) and certain forms of epilepsy.

Another use of proteomics in this new CF Foundation strategy involves identifying proteins that could function as "biomarkers" of the disease's status, such as a patient's degree of lung damage or response to treatment. These studies will be carried out at several other institutions and companies.


The Cystic Fibrosis Foundation was created in 1955 to assure the development of the means to cure and control CF and to improve the quality of life for people with the disease. The CF Foundation's proteomics research initiative is part of its innovative Therapeutics Development Program, which supports the full spectrum of CF drug development from discovery to clinical evaluation. Matching milestone-driven grants to support CF drug discovery and development are offered to biotechnology companies and academic institutions through this program. Promising new drugs are then streamlined through clinical trial evaluations in the CF Foundation's network of specialized care centers.

CFFTI is a nonprofit affiliate of the CF Foundation that operates drug discovery, development and evaluation efforts. CFFTI is made up of industry and academic researchers and members of the CF Foundation Board of Trustees. Total support of CFFTI is provided by the CF Foundation. For more information on the CF Foundation and CFFTI, please visit