Projects

Cystic fibrosis (CF), a life-shortening disease, is the most common monogenic disorder, caused by mutations in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene, encoding a chloride channel in the apical membrane of epithelial cells. There is an urgent need for novel therapies as current CFTR modulators either target a small patient group, or show moderate efficacy. Most patients only receive symptomatic treatment. To cure ...

The intestinal microbiota plays an important role in health and disease of humans. Cystic fibrosis patients suffer from lung infections that require multiple antimicrobial therapies. In addition, their intestinal physiology and food digestion are severely disturbed. The present project will use metaproteomics analyses to study the composition, dynamics and other characteristics of the distal microbiota of a cohort of cystic fibrosis patients ...

Unpublished epidemiologic study results indicate that only certain Pseudomonas aeruginosa strains, marked by specific alleles of the oprD porine protein encoding gene are able to colonize cystic fibrosis patients. Construction of different OprD mutants and infection with these bacterial strains of different in vitro airway epithelial cell line cultures willenable to elucidate the role of this porin in internationalisation of this bacterium in ...

Cystic fibrosis (CF) remains a burdening genetic disease. Female CF patients are confronted with decreased fertility, experiencing difficulties in getting pregnant. Underlying reasons remain largely unclear. In particular, it has only poorly been studied whether the endometrium, the inner lining of the womb and crucial tissue for embryo implantation, plays a role. This gap is mainly due to lack of appropriate study models. Recently, we ...

Cystic fibrosis (CF) is the most common life-shortening monogenic disorder causing multi-organ disease. CF is caused by mutations in the CFTR gene, which encodes a Cl-/HCO3- channel expressed in the apical membrane of epithelial cells. Current small molecule treatment is available to ~60% of CF patients and with new modulators in the pipeline, potentially 90% of CF patients can be treated. The last 10%, i.e. the minimal function mutations, ...

Cystic fibrosis (CF) patients suffer from severe lung infection and inflammation, which leads to
irreversible lung damage and death. As CF is the most common life shortening condition in
Caucasians, there is an urgent need to develop novel therapies.
The focus has mainly been on remedies to improve airway clearance and antibiotics to treat
infections, with limited success. There is a growing interest in addressing the ...

In Europe, CF is the most common life shortening inherited disorder. Median survival is 37 years. Most patients die from lung disease (CFLD).
Much can be gained from prevention or better treatment of early CFLD. Since CF newborn screening is available in many European countries, this task becomes even more important. CFLD is thought to affect the small airways early in life. So far no one has managed to directly show this as the small ...

Fungal infections in a context of pre-existing immunodeficiency or lung disease are often life-threatening complications, but our knowledge on the interplay of pathogen and host factors involved still contains important therapeutic, methodological and fundamental gaps. Resistance against current antifungal therapy urges us to find alternatives. Host factors inhibit or facilitate infection dissemination, and we lack insight in this paradoxical ...

The high attrition rate in drug development is a major issue for the pharmaceutical industry. Of particular concern is the high failure rate in clinical phase 2 and 3. At this point, failure is disastrous from an economic point of view, leading to an outrageous general cost to bring a compound to the market. Providing predictive in vitro tests in a preclinical stage is generally acknowledged to lower the chances of failure in clinical phases. ...