Project description:Identificaiton of novel single-nucleotide polymorphism (SNP) candidates associated with chemo-responsiveness in colorectal cancers using microarray Response rates of 104 colorectal cancer patients to established regiments (FL, CAPE, FLOX, FLIRI) were evaluated by histoculture drug response assay. Affymetrix SNP 5.0 chips were used to determine genotypes of the same colorectal cancer patients. SNPs associated with chemosensitivity to standard regimens were identified by genome-wide association study. FL: 5-FU + Leucovorin; CA: Capecitabine, FLOX: 5-FU + Leucovorin + Oxaliplatin, FLIRI: 5-FU + Leucovorin + Irinotecan
Project description:A core task to understand the consequences of non-coding single nucleotide polymorphisms (SNP) is to identify their genotype specific binding of transcription factor (TF). Here, we generate a large-scale TF-SNP interaction map for a selection of 116 colorectal cancer (CRC) risk loci and validated TF binding to 10 putatively functional SNPs. Our data further revealed TF binding complexity adjacent to the 116 risk loci, adding an additional layer of understanding to regulatory networks associated with CRC relevant loci.
Project description:Environmental Enteric Dysfunction (EED) is a chronic inflammatory condition of the intestine characterized by villus blunting, compromised intestinal barrier function, and reduced nutrient absorption. Here, we show that key genotypic and phenotypic features of EED-associated intestinal injury can be reconstituted in a human intestine-on-a-chip (Intestine Chip) microfluidic culture device lined by organoid-derived intestinal epithelial cells from EED patients and cultured in nutrient deficient medium lacking niacinamide and tryptophan (-N/-T). Exposure of EED Intestine Chips to -N/-T deficiencies resulted in transcriptional changes similar to those seen in clinical EED patient samples including congruent changes in six of the top ten upregulated genes. Exposure of EED Intestine Chips or chips lined by healthy intestinal epithelium (healthy Intestine Chips) to -N/-T medium resulted in severe villus blunting and barrier dysfunction, as well as impairment of fatty acid uptake and amino acid transport.