Project description:This multi-center study will compare multi-target DNA and quantitative FIT stool-based testing to colonoscopy in individuals with Cystic Fibrosis (CF) undergoing colon cancer screening with colonoscopy. The primary endpoint is detection of any adenomas, including advanced adenomas and colorectal cancer (CRC).
Project description:Lung disease is the main cause of morbidity and mortality in cystic fibrosis (CF), and involves chronic infection by a destructive microbiota and perturbed innate and adaptive immune responses. Tissue damage is considered to be mediated mostly by proteases, but other bacterial and host factors may also play a role. To determine the presence of potentially injurious proteins we employed semi-quantitative Multidimensional Protein Identification Technology to identify sputum cellular proteins with consistently altered expression in CF compared to healthy controls. Ingenuity Pathway Analysis, Gene Ontology functions, protein abundance and correlation with lung function were used to infer their clinical significance. The CF proteome exhibited differential expression of proteins relating to Rho family small GTPase activity, immune cell movement and activation, generation of reactive oxygen species and dysregulation of cell death and proliferation. Compositional breakdown established neutrophil extracellular trap proteins as the consistently most abundant cellular proteins detected, while a further 13 biologically relevant proteins were found to correlate negatively with lung function. These findings expand the current understanding of the mechanisms underlying CF lung disease and identify sputum cell proteins which might be useful as markers of disease status, prognostic indicators, stratification determinants for treatment prescription or as therapeutic targets.
Project description:We characterized the transcriptional responses of three S. maltophilia strains during exposure to synthetic CF sputum media (SCFM2) to gain insight into how this organism interacts with the host in the CF lung. These efforts led to the identification of 881 transcripts differentially expressed by all three strains, many of which reflect different metabolic pathways used by S. maltophilia in sputum, and altered stress responses. The latter correlated with increased resistance to peroxide exposure after pre-growth in SCFM2. We also compared the SCFM2 transcriptomes of two S. maltophilia CF isolates with the SCFM2 transcriptome of the acute infection model strain, S. maltophilia K279A, allowing us to identify CF isolate-specific signatures in differential gene expression that may be suggestive of adaptation to the CF lung. Each strain also possessed genes not shared by the other two and here we show that expression of some of the accessory genes in each strain are changed in response to SCFM2. Collectively, this work details the response of S. maltophilia to the CF lung environment, identifying potential survival strategies and metabolic pathways used by S. maltophilia during infections.