Project description:To analyze the expression profile of polycystic kideny disease, we generate RNASeq data on Pkd1-mutant mice.RNA sequencing was done on 5 Wild-type (Wt) mice and kidneys of 4 iKsp-Pkd1del mice with gene disruption at the age of 38-40 days (Mutant). Mutant mice, sacrificed 84 days later, had moderate cystic disease. To analyze the expression profiles of injury repair, renal injury was induced one week after tamoxifen administration by a single i.p. injection of S-(1,2-dichlorovinyl)-L-cysteine (DCVC) (15mg/kg). Mice were sacrificed at determined time points (1,2, 5,10 and 24 weeks after DCVC injection). RNA sequencing was performed on the DCVC injected Wt mice sacrificed at 1, 2 and 5 weeks after DCVC (4 mice per each time point).
Project description:Trichloroethylene (TCE) is an industrial solvent and widespread environmental contaminant. Human TCE exposure is prevalent, though epidemiological studies testing TCE exposure and adverse birth outcomes are inconclusive. The TCE metabolite S-(1,2-dichlorovinyl)-L-cysteine (DCVC) exhibits toxicity at human-relevant concentrations in a placental cell line. To date, DCVC cytotoxicity mechanistic studies have been limited to single molecular signaling pathways and biological responses. In the current study, genome-wide gene expression and gene set enrichment analyses (GSEA) were used to identify novel genes and pathways altered by human exposure-relevant DCVC concentrations in human placental villous explant tissues. The results of this study were compared to a parallel study using the placental cell line HTR-8/SVneo.
Project description:Trichloroethylene (TCE) is an industrial solvent and widespread environmental contaminant. Human TCE exposure is prevalent, though epidemiological studies testing TCE exposure and adverse birth outcomes are inconclusive. The TCE metabolite S-(1,2-dichlorovinyl)-L-cysteine (DCVC) exhibits toxicity at human-relevant concentrations in a placental cell line. To date, DCVC cytotoxicity mechanistic studies have been limited to single molecular signaling pathways and biological responses. In the current study, genome-wide gene expression and gene set enrichment analyses (GSEA) were used to identify novel genes and pathways altered by human exposure-relevant DCVC concentrations in the human placental cell line HTR-8/SVneo. The results of this study were compared to a parallel study using placental villous exlant tissues.
Project description:Assessment of diet currently relies on self-reporting, such as food logs, 24 hour recalls and food frequency questionnaires. Self-reporting of diet is inaccurate due to memory lapses, lying and biased language. A molecular-based approach to assess diet would allow accurate reporting of diet for researchers, medical professionals and patients. We performed metaproteomic analysis of 22 human stool samples collected from four individuals enrolled at the Duke Diet and Fitness Center. Samples were collected between 01Aug19 and 22Nov19. All meals at the Duke Diet and Fitness Center were recorded such that the approximate quantities of each food item consumed are known.
Project description:Volatile organic chemicals Trichloroethylene (TCE) and perchloroethylene (PCE) are liquid solvents used for dry cleaning, industrial degreasing operations, and more. The multiple industrial uses of TCE and PCE have led to large volumes of TCE and PCE being released into the air, surface water, groundwater, and soil worldwide. Maternal exposure to TCE and/or PCE are associated with increased risk of restricted fetal growth (TCE), preterm birth (PCE), placental abruption (PCE) and stillbirth (PCE), suggesting that the placenta may be a key target of TCE and PCE due to its critical role in maintaining maternal and fetal health in pregnancy and mediating fetal growth. We previously showed that TCE and PCE metabolites activate stress response and cell death pathways in placental cell and tissue models. However, there are still key gaps in our knowledge on TCE and PCE metabolites impact the placenta, particularly across fetal sex. We aimed to identify transcriptomic responses to the TCE metabolite S-(1,2-dichlorovinyl)-L-cysteine (DCVC) and PCE metabolite S-(1,2,2-trichlorovinyl)-L-cysteine (TCVC) using a placental explant model and to determine the extent to which fetal sex modifies DCVC and TCVC impacts on the transcriptome. We isolated both male- and female-associated villous placental tissue (n=8, four male and four female), followed by treatment with DCVC or TCVC at the following concentrations: 0 μM (control), 10 μM, and 20 μM. Following treatment, we isolated RNA from explants and generated whole transcriptome profiles using RNA sequencing. We conducted differential gene expression analysis to identify significant gene expression changes across treatment groups, stratified by fetal sex (adjusted p-value < 0.05 and |log2 fold change| > 1). We performed Gene Set Enrichment Analysis (GSEA) to evaluate differences in biological pathway enrichment across treatment groups. Finally, we performed placental cell type deconvolution using CIBERSORTx and used beta regression to compare proportions of cell types between VOC-metabolite exposed tissue and unexposed tissue in both fetal sexes. Significant gene expression changes for both fetal sexes were observed across all treatment groups compared to controls.
Project description:Expression profiling of whole blood cells isolated from patients piror to undergoing cardiac catheterization. The Cathgen Registry is a single-center coronary catheter-lab cohort being run at Duke University for the purpose of identifying biomarkers associated with coronary disease.
Project description:Normal kidney, liver, spleen, and Universal RNA from Stratagene were expression profiled across five centers (UCLA, Duke, TGen, Children's National Medical Center in Washington, DC, and University of Pennsylvania) using the Affymetrix, spotted Operon, Agilent, and Amersham arrays to identify differences in expression between microarray platforms as well as centers. To compare the four microarray platforms as well as the reproducibility across the centers. There will be expression differences between the five centers. The following array types were profiled at the centers: UCLA: Affymetrix, Amersham, Agilent TGen: Affymetrix (3000 scanner) Children's: Affymetrix (2500 scanner) Duke: Operon Oligo University of Penn.: Affymetrix Series_author: Consortium,,Cross Platform Keywords: other