Vaccine research today is focused on using safer, highly purified or recombinant antigens with poor immunogenicity, which has created a need for potent adjuvants. Rational design of effective and safe mucosal adjuvants for human use necessitates a thorough understanding of the mode of action of successful candidate adjuvants.
Unraveling molecular signatures of immunostimulatory adjuvants in the female genital tract through systems biology.
Sex, Treatment
View SamplesNotch signaling is an important regulator of stem cell differentiation. All canonical Notch signaling is transmitted through the DNA-binding protein CSL and hyperactivated Notch signaling is associated with tumor development; thus it may be anticipated that CSL deficiency should reduce tumor growth. In contrast, we report that genetic removal of CSL in breast tumor cells caused accelerated growth of xenografted tumors. Loss of CSL unleashed a hypoxic response during normoxic conditions, manifested by stabilization of the HIF1± protein and acquisition of a polyploid giant-cell, cancer stem cell-like, phenotype. At the transcriptome level, loss of CSL upregulated more than 1750 genes and less than 3% of those genes were part of the Notch transcriptional signature. Collectively, this suggests that CSL exerts functions beyond serving as the central node in the Notch signaling cascade and reveals a novel role for CSL in tumorigenesis and regulation of the cellular hypoxic response. Overall design: CSL +/+ and CSL -/- MDA-MB-231 were subjected to Notch activation/inhibition and xenograft experiment. Total RNA were extracted from the samples and sent to NGS. Single Cell RNA-sequencing was also performed from cells isolated from xenograft tumors.
Loss of CSL Unlocks a Hypoxic Response and Enhanced Tumor Growth Potential in Breast Cancer Cells.
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View SamplesMicroarray based mRNA profiling was used to identify the mechanism of action for the small molecule b-AP15.
Inhibition of proteasome deubiquitinating activity as a new cancer therapy.
Cell line, Treatment
View SamplesVitamin A is the only known compound that produces spontaneous fractures in rats. In an effort to resolve the molecular mechanism behind this effect, we fed young rats high doses of vitamin A and performed a global transcriptional analysis of diaphyseal bone after one week, i.e. just before the first fractures appeared. Microarray gene expression analysis revealed that 68 transcripts were differentially expressed in hypervitaminotic cortical bone and 118 transcripts were found when the bone marrow was also included. 98% of the differentially expressed genes in the bone marrow sample were up-regulated. In contrast, hypervitaminotic cortical bone without marrow showed reduced expression of 37% of differentially expressed genes. Gene Ontology (GO) analysis revealed that only samples containing bone marrow were associated to a GO term, which principally represented extracellular matrix (ECM). This is consistent with the histological findings of increased endosteal bone formation. Four of the genes in this ECM cluster and four other genes, including Cyp26b1 which is known to be up-regulated by vitamin A, were selected and verified by real-time PCR. In addition, immunohistochemical staining of bone sections confirmed that the bone-specific molecule, osteoadherin (Omd) was up-regulated. Further analysis of the major gene expression changes revealed distinct differences between cortical bone and bone marrow, e.g. there appeared to be augmented Wnt signaling in the bone marrow but reduced Wnt signaling in cortical bone. Moreover, induced expression of hypoxia-associated genes was only found in samples containing bone marrow. Together, these results corroborate our previous observations of compartment-specific effects of vitamin A, with reduced periosteal but increased endosteal bone formation, and suggest important roles for Wnt signaling and hypoxia in the processes leading to spontaneous fractures.
Microarray profiling of diaphyseal bone of rats suffering from hypervitaminosis A.
Sex, Age, Specimen part, Disease
View SamplesWe performed microarray analysis to investigate the gene expression profile changes induced by Hmg20b knock down in I/11 cells.
The DNA binding factor Hmg20b is a repressor of erythroid differentiation.
Specimen part
View SamplesHeat shock timecourse RNAseq, 3T3 cells
Widespread inhibition of posttranscriptional splicing shapes the cellular transcriptome following heat shock.
No sample metadata fields
View SamplesThe specific contribution of the two TNF-receptors Tnfr1 and Tnfr2 to TNF-induced inflammation in the glomerulus is unknown. In mice, TNF exposure induces glomerular expression of inflammatory mediators like adhesion molecules and chemokines in vivo, and glomerular accumulation of leukocytes.
Distinct contributions of TNF receptor 1 and 2 to TNF-induced glomerular inflammation in mice.
Specimen part, Treatment
View SamplesTranscriptome study of 2 Saccharomyces cerevisiae W303 derivatives, one carrying GFP (control) and one carrying aSyn-GFP
Different 8-hydroxyquinolines protect models of TDP-43 protein, α-synuclein, and polyglutamine proteotoxicity through distinct mechanisms.
Specimen part, Disease, Cell line
View Samples593 FFPE colorectal cancer samples were used to generate three prediction models: Recurrence prediction, 5FU efficacy prediction, and FOLFOX efficacy prediction
Building personalized treatment plans for early-stage colorectal cancer patients.
Specimen part
View SamplesExpression profiling of cultured HL-1 cardiomyocytes subjected to hypoxia for 8 hours.
The VLDL receptor promotes lipotoxicity and increases mortality in mice following an acute myocardial infarction.
Cell line
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