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Research GroupsPathogenesis and treatment of cystic fibrosis

Background Details

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We joined the MMPU in 2006 to coordinate our longstanding interest in research related to the pathogenesis and treatment of cystic fibrosis (CF) lung disease. CF belongs to the most common lethal hereditary disease in Caucasians and is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which result in characteristic defects in epithelial ion transport (i.e. decreased cAMP-mediated Cl- secretion and increased Na+ absorption).

To determine the role of accelerated Na+ absorption in the in vivo pathogenesis of CF lung disease, Marcus Mall has previously developed a transgenic mouse model with airway-specific overexpression of epithelial sodium channels (ENaC). This mouse model recapitulates increased airway Na+ absorption observed in CF patients, and demonstrated that dehydration of airway surfaces causes a severe spontaneous CF-like lung disease that shares many features with CF in humans, including airway mucus obstruction, goblet cell metaplasia, chronic inflammation and susceptibility to bacterial infection (Mall. M. et al, Nat. Med., 2004; Mall. M. et al, Am J Respir Crit Care Med, 2008).

The prior focus of Carsten Schultz was on the development and in vitro testing of small molecule compounds that target epithelial signaling to correct for the basic ion transport defect in CF airways. This work resulted in membrane-permeant derivatives of myo-inositol 3,4,5,6-tetrakisphosphate, a class of compounds that have been shown to counteract the basic ion transport defect in CF (Moody, M. et al, Am. J. Physiol. Cell Physiol., 2005; Traynor-Kaplan, A.E. et al, Adv. Exp. Med. Biol., 2005). Since the implementation at the EMBL in 2001, the Schultz lab has developed extensive experience in generating fluorescent sensors to monitor enzyme activities and intracellular signaling events in living cells.

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