Project description:Exposure to Polychlorobiphenyls (PCBs) is known to cause serious health effects in human but the gene expression profiles leading to development of differnet diseases and disorders are not fully understood. The knowledge of global gene expression will help us to devlop early disease or disorder biomarkers for PCB induced health effects. We used microarrays to detail the global gene expression profile underlying the effects of PCB 153 exposure to human PBMC leading to identification of distinct classes of up-regulated and down-regulated genes and cellular processes.
Project description:In order to investigate the underlying mechanisms of PCB 153 mediated toxicity to Atlantic cod (Gadus morhua), we analyzed the liver proteome of fish exposed to various doses of PCB 153 (0, 0.5, 2 and 8mg/kg body weight) for two weeks and examined the effects on expression of liver proteins using quantitative proteomics. Label-free mass spectrometry enabled quantification of 1272 proteins, and 78 were differentially regulated between PCB 153 treated samples and controls. Two proteins downregulated due to PCB 153 treatment, Glutathione S-transferase theta 1 (GSTT1) and sulfotransferase family protein 1 (ST2B1), were verified using selected reaction monitoring (SRM). Supported by bioinformatics analyses, we concluded that PCB 153 perturbs lipid metabolism in the Atlantic cod liver and that increased levels of lipogenic enzymes indicate increased synthesis of fatty acids and triglycerides.
Project description:Exposure to Polychlorobiphenyls (PCBs) is known to cause serious health effects in human but the gene expression profiles leading to development of differnet diseases and disorders are not fully understood. The knowledge of global gene expression will help us to devlop early disease or disorder biomarkers for PCB induced health effects. We used microarrays to detail the global gene expression profile underlying the effects of PCB 153 exposure to human PBMC leading to identification of distinct classes of up-regulated and down-regulated genes and cellular processes. PBMC cells are grown for 48 hours in RPMI 1640 supplemented with 10% FBS and 1X Pennicilllin-Streptromycin with 1.25 mircogram/ml PHA-M and 0.15% (v/v)pokeweed mitogen and 50 microgram Beta-mercaptoethanol.Trizol extraction of total RNA was performed according to the manufacturer's instructions. Biotinylated cRNA were prepared according to the standard Affymetrix protocol from 6 microgram of total RNA (Expression Analysis Technical Manual, 2001, Affymetrix). Following fragmentation, 10 microgram of cRNA were hybridized for 16 hr at 45C on GeneChip Human Genome Array (HGU133 plus 2.0). GeneChips were washed and stained in the Affymetrix Fluidics Station 450 and scanned using the Affymetrix GeneArray Scanner 3000. The data were analyzed with Microarray Suite version 5.0 (MAS 5.0) using Affymetrix default analysis settings and global scaling as normalization method. The trimmed mean target intensity of each array was arbitrarily set to 150.
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
Project description:Purpose: to investigate transcriptomal differences between wild-type and SXR/PXR knockout mice and the impact of PCB-153 exposure to both strains to help reveal the mechanism behind the phenotype of hemolytic anemia observed in SXR knockout mice exposed to PCB-153
Project description:Exposure to Polychlorobiphenyls (PCBs) is known to cause serious health effects in human but the gene expression profiles leading to development of differnet diseases and disorders are not fully understood. The knowledge of global gene expression will help us to devlop early disease or disorder biomarkers for PCB induced health effects. We used microarrays to detail the global gene expression profile underlying the effects of PCB 138 exposure to human PBMC leading to identification of distinct classes of up-regulated and down-regulated genes and cellular processes. Keywords: PCB 138 Exposures
Project description:Killifish (Fundulus heteroclitus) inhabiting the New Bedford Harbor (NBH) Superfund Site have evolved resistance to the toxic and biochemical effects of non-ortho (dioxin-like) polychlorinated biphenyls (DL-PCBs) and other compounds that act via the aryl hydrocarbon receptor (AHR) signaling pathway. However, the majority of PCBs in NBH are ortho-substituted (non-DL) PCBs (o-PCBs), and the impacts of these o-PCBs on fish populations are not well understood. To determine whether the NBH killifish population has adapted to o-PCBs, we performed a series of experiments involving exposure to killifish embryos and adults from NBH and a reference site (Scorton Creek; SC) to 2,2’,4,4’,5,5’-hexachlorobiphenyl (PCB-153), a model o-PCB. PCB-153 was not acutely embryotoxic to developing F2 killifish embryos (SC or NBH) at concentrations up to 28 µM. RNA-seq showed that SC embryos exposed to PCB-153 (28 µM for 6 hr at 10 days post fertilization) had changes in the expression of genes involved in glucose homeostasis. However, NBH embryos were much less sensitive to these effects of PCB-153. When adult killifish from SC and NBH were exposed to PCB-153 (20 mg/kg) and sampled 3 days later for gene expression, many more genes were affected in forebrains of SC fish than in NBH fish, in a sex-specific manner. Together, these results demonstrate that NBH killifish have evolved reduced sensitivity to o-PCBs, suggesting complex adaptation to chemical mixtures at a Superfund site.
Project description:Transcriptional profiling of human mesenchymal stem cells comparing normoxic MSCs cells with hypoxic MSCs cells. Hypoxia may inhibit senescence of MSCs during expansion. Goal was to determine the effects of hypoxia on global MSCs gene expression.