- B.S., University of Regensburg, 1991
- M.S., University of Regensburg, 1993
- Ph.D., University of Regensburg, 1997
- Post-doc, University of Regensburg, 1997-98
- Post-doc, Mayo Clinic Scottsdale, AZ, 1998-01
- Research Associate, Mayo Clinic, 2001-05
- Cystic Fibrosis Foundation
- Else Kröner-Fresenius-Stiftung
- National Institutes of Health
- Research Contracts Companies
Cystic fibrosis is a disease of defective epithelial salt and fluid transport that is caused by mutations in CFTR (cystic fibrosis transmembrane conductance regulator). A major focus of my research is the biosynthetic processing and intracellular trafficking of CFTR. This multi-domain protein functions as a chloride channel in apical membranes of epithelial cells and in addition regulates other ion channels and transporters. More than 1500 different mutations in the CFTR gene have been identified in cystic fibrosis patients, however, a deletion of phenylalanine 508 (DF508) is most common and present in more than 90% of cystic fibrosis patients. The misfolded protein DF508 cannot mature conformationally and is recognized by ER quality control and therefore is not able to proceed to Golgi and plasma membrane. Growth of cells at reduced temperature or other manipulations enable the nascent mutant protein to avoid ER quality control and reach the cell surface, but it is rapidly cleared from the distal secretory pathway and degraded in lysosomes. Rescue of DF508 CFTR from ER retention is currently being intensively pursued as a potential therapeutic approach to alleviate cystic fibrosis disease. Our lab has a specific interest in the endocytic trafficking of rescued DF508 CFTR and we have recently found that rescue of the mutant protein from ER retention by some means affects endocytic routing of other components e.g. cholesterol and glycosphingolipids.
The long-term goal of the laboratory is to augment CFTR function in cystic fibrosis airways by understanding the underlying cellular and molecular mechanisms that determine the efficacy of mutant CFTR rescue in vivo.
We employ multiple modern molecular, biochemical, electrophysiological and cellular biology techniques and relevant pre-clinical in vitro, ex vivo and in vivo models for our studies.
We are currently working on the following projects:
- Pharmacological rescue of mutant CFTR
- Impact of environmental factors on mutant CFTR rescue
- CFTR-mediated regulation of the Epithelial Sodium Channel (ENaC)
- Development of novel preclinical models and methodology