This experiment aims to identify the biological pathways and diseases associated with the cytokine Interleukin 13 (IL-13) using gene expression measured in peripheral blood mononuclear cells (PBMCs). Overall design: The experiment comprised of samples obtained from 3 healthy donors. The expression profiles of in vitro IL-13 stimulation were generated using RNA-seq technology for 3 PBMC samples at 24 hours. The transcriptional profiles of PBMCs without IL-13 stimulation were also generated to be used as controls. An IL-13R-alpha antagonist (Redpath et al. Biochemical Journal, 2013) was introduced into IL-13 stimulated PBMCs and the gene expression levels after 24h were profiled to examine the neutralization of IL-13 signaling by the antagonist.
Combining multiple tools outperforms individual methods in gene set enrichment analyses.
No sample metadata fields
View SamplesBacillus anthracis, the causative agent of anthrax, secretes three toxin proteins: protective antigen (PA), lethal factor (LF), and edema factor (EF). PA is a transporter of LF and EF into host cells by receptor-mediated endocytosis. LF is a metalloprotease that cleaves mitogen-activated protein kinase (MAPK) kinases (MKK), while EF is an adenylate cyclase, which converts ATP to cAMP.
Antiinflammatory cAMP signaling and cell migration genes co-opted by the anthrax bacillus.
No sample metadata fields
View SamplesThe NFB transcription factor is constitutively active in a number of hematologic and solid tumors, and many signaling pathways implicated in cancer are likely connected to NFB activation. A critical mediator of NFB activity is TGF-activated kinase 1 (TAK1). Here, we identify TAK1 as a novel interacting protein and direct target of fibroblast growth factor receptor 3 (FGFR3) tyrosine kinase activity.
Fibroblast growth factor receptor 3 interacts with and activates TGFβ-activated kinase 1 tyrosine phosphorylation and NFκB signaling in multiple myeloma and bladder cancer.
Specimen part, Cell line
View SamplesRNA-seq analysis was performed between WT and alphaT-cat KO mouse cerebella aiming to discover gene transcripts altered by the loss of alphaT-cat These altered gene transcripts could be associated with several neurologic disease-relevant pathways Overall design: Total RNA extracted of cerebellar tissue (n=3) from the brains of WT ad alphaT-cat KO mice
αT-catenin in restricted brain cell types and its potential connection to autism.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
T-cell Receptor Signaling Activates an ITK/NF-κB/GATA-3 axis in T-cell Lymphomas Facilitating Resistance to Chemotherapy.
Specimen part, Disease stage, Cell line
View SamplesTo study differential gene expression of TCLs upon TCR signaling, three TCL primary cells and one TCL cell line T8ML1 were chosen for this study. The prmiary TCL cells consist of TCL1 and TCL2 (sezary patients) and TCL3 (PTCL, NOS patient). The TCR signaling was engaged by anti-CD3/CD28 treatment in vitro. The TCL cells were treated without/with anti-CD3/CD28 for different time periods in vitro in cell culture. The total RNA was isolated from the TCLs and subjected to affimetry microarray (GPL17692) analysis. The differential gene expression of individual TCL was identified as well as a set of common genes invloved in TCR signaling in TCLs.
T-cell Receptor Signaling Activates an ITK/NF-κB/GATA-3 axis in T-cell Lymphomas Facilitating Resistance to Chemotherapy.
Specimen part, Disease stage, Cell line
View SamplesTreating unselected cancer patients with new drugs dilutes proof of efficacy when only a fraction of patients respond to therapy. We conducted a meta-analysis on eight primary breast cancer microarray datasets representing diverse breast cancer phenotypes. We present a high-throughput protocol which incorporates drug sensitivity signatures to guide preclinical testing for effective therapeutic agents. Specifically, we focus on drug classes currently undergoing early phase clinical testing. Our genomic and experimental results suggest that the majority of basal-like breast cancers should respond to inhibitors of the phosphatidylinositol-3-kinase pathway, and that a relatively low toxicity histone deacetylase inhibitor, valproic acid, may target aggressive breast cancers. For a subset of drugs, prediction of sensitivity associates with tumor recurrence, suggesting clinical relevance. Preclinical studies using both cell lines and patient tumors grown in 3-dimensional in vitro and orthotopic in vivo preclinical models provide an efficient and highly relevant assessment of drug sensitivity in tumor phenotypes, and validate our genomic analyses. Together, our results show that high-throughput transcriptional profiling can significantly impact drug selection for breast cancer patients. Pre-identification of patient response may not only improve therapeutic response rates, it can also assist in quickly identifying the optimal inclusion criteria for clinical trials. Our model facilitates personalized drug therapy for cancer patients and may be generalized for study of drug efficacy in other diseases.
A pharmacogenomic method for individualized prediction of drug sensitivity.
Specimen part
View SamplesThe ARV1-encoded protein mediates sterol transport from the endoplasmic reticulum (ER) to the plasma membrane. Yeast ARV1 mutants accumulate multiple lipids in the ER and are sensitive to pharmacological modulators of both sterol and sphingolipid metabolism. Using fluorescent and electron microscopy, we demonstrate sterol accumulation, subcellular membrane expansion, elevated lipid droplet formation and vacuolar fragmentation in ARV1 mutants. Motif-based regression analysis of ARV1 deletion transcription profiles indicates activation of Hac1p, an integral component of the UPR. Accordingly, we show constitutive splicing of HAC1 transcripts, induction of a UPR reporter and elevated expression of UPR targets in ARV1 mutants. IRE1, encoding the unfolded protein sensor in the ER lumen, exhibits a lethal genetic interaction with ARV1, indicating a viability requirement for the UPR in cells lacking ARV1. Surprisingly, ARV1 mutants expressing a variant of Ire1p defective in sensing unfolded proteins are viable. Moreover these strains also exhibit constitutive HAC1 splicing that interacts with DTT-mediated perturbation of protein folding. These data suggest a component of UPR induction in arv1? strains is distinct from protein misfolding. Decreased ARV1 expression in murine macrophages also results in UPR induction, particularly up-regulation of activating transcription factor-4, C/EBP homologous protein (CHOP) and apoptosis. Cholesterol loading or inhibition of cholesterol esterification further elevated CHOP expression in ARV1 knockdown cells. Thus, loss or down-regulation of ARV1 disturbs membrane and lipid homeostasis resulting in a disruption of ER integrity, one consequence of which is induction of the UPR.
Loss of subcellular lipid transport due to ARV1 deficiency disrupts organelle homeostasis and activates the unfolded protein response.
No sample metadata fields
View SamplesTo study differential gene expression of TCLs upon TCR signaling, three TCL primary cells and one TCL cell line T8ML1 were chosen for this study. The prmiary TCL cells consist of TCL1 and TCL2 (sezary patients) and TCL3 (PTCL, NOS patient). The TCR signaling was engaged by anti-CD3/CD28 treatment in vitro. The TCL cells were treated without/with anti-CD3/CD28 for different time periods in vitro in cell culture. The total RNA was isolated from the TCLs and subjected to affimetry microarray (GPL17692) analysis. The differential gene expression of individual TCL was identified as well as a set of common genes invloved in TCR signaling in TCLs.
T-cell Receptor Signaling Activates an ITK/NF-κB/GATA-3 axis in T-cell Lymphomas Facilitating Resistance to Chemotherapy.
Specimen part, Disease stage
View SamplesTo study differential gene expression of TCLs upon TCR signaling, three TCL primary cells and one TCL cell line T8ML1 were chosen for this study. The prmiary TCL cells consist of TCL1 and TCL2 (sezary patients) and TCL3 (PTCL, NOS patient). The TCR signaling was engaged by anti-CD3/CD28 treatment in vitro. The TCL cells were treated without/with anti-CD3/CD28 for different time periods in vitro in cell culture. The total RNA was isolated from the TCLs and subjected to affimetry microarray (GPL17692) analysis. The differential gene expression of individual TCL was identified as well as a set of common genes invloved in TCR signaling in TCLs.
T-cell Receptor Signaling Activates an ITK/NF-κB/GATA-3 axis in T-cell Lymphomas Facilitating Resistance to Chemotherapy.
Specimen part, Disease stage
View Samples