In many epithelial tissues, the protein mainly responsible for controlling transepithelial fluid movement is the the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR was originally identified as the protein product of the gene causing cystic fibrosis (CF). CFTR functions as a chloride channel regulated by protein kinase A (PKA). This laboratory is studying the role and regulation of CFTR. One project focuses on how PKA acts on CFTR. In this project, recombinant peptide models are being used to model the cytoplasmic domains of CFTR responsible for activating the protein's chloride's chloride channel function. Site-directed mutagenesis is being used to produce modified peptides to study how different individual serine phosphoryation contribute to CFTR regulation. A second project concerns DF508, the most common mutation among patients with CF. This mutation affects CFTR function by preventing normal folding and intracellular trafficking of the newly synthesized mutant protein. This project is examining the mislocalization of DF508-CFTR in tissues and cell lines with the long term goal of developing strategies to prevent the mutant protein from mislocalizing. A third project concerns the role of CFTR in chronic pancreatitic diseases. Emerging data about the role of CFTR during normal pancreatic secretion suggests that dysfunction of this protein may lead to pancreatic diseases such as chronic pancreatitis and pancreatic cancer. Patients with these chronic pancreatic diseases are being tested for CFTR mutations and for evidence of defective CFTR function.
Education and Training
- Fellow in Gastroenterology, Medicine, Yale University, 1981 - 1984
- Medical Resident, Medicine, University of California, San Francisco, School of Medicine, 1980 - 1981
- Medical Resident, Medicine, University of Alabama at Birmingham, 1978 - 1980
- M.D., Cornell University, 1978