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Escherichia coli
17 Downloadable Samples
Affymetrix E. coli Genome 2.0 Array (ecoli2)
Description
We treated logarithmically growing cultures of E.coli with a sub-lethal dose of an antimicrobial arylamide compound (PMX 10070) and Polymyxin B sulfate to measure transcriptional responses in an effort to understand mechanism of action
Publication Title
Antibacterial mechanism of action of arylamide foldamers.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 27 Downloadable Samples
- Affymetrix Rat Gene 2.0 ST Array (ragene20st)
Description
Complete global brain ischemia (CGBI) and reperfusion occur following resuscitation from cardiac arrest. Different brain neurons are selectively vulnerable to CGBI: pyramidal neurons of hippocampal CA3 survive 10 min CGBI but those of CA1 die at 3 days following 10 min CGBI. CA3 neurons are expected to have more robust stress responses and repair responses than CA1 neurons.
Publication Title
Embryonic lethal abnormal vision proteins and adenine and uridine-rich element mRNAs after global cerebral ischemia and reperfusion in the rat.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 21 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
We previously identified toll-like receptor 4 (Tlr4) as a candidate gene responsible for ozone (O3)-induced pulmonary hyperpermeability and inflammation. The objective of this study was to determine the mechanism through which TLR4 modulates O3-induced pulmonary responses and to utilize transcriptomics to determine TLR4 effector molecules. C3H/HeJ (HeJ; Tlr4 mutant) and C3H/HeOuJ (OuJ; Tlr4 normal), mice were exposed continuously to 0.3 ppm O3 or filtered air for 6, 24, 48 or 72 hr. Affymetrix Mouse430A_MOE gene arrays were used to analyze lung homogenates from HeJ and OuJ mice followed using a bioinformatic analysis. Inflammation was assessed by bronchoalveolar lavage and molecular analysis by ELISA, immunoblotting, and transcription factor activity. TLR4 signals through both the MYD88-dependent and independent pathways in OuJ mice, which involves MAP kinase activation, NF-kappaB, AP-1, and KC. Microarray analyses identifiedTLR4 responsive genes for strain and time in OuJ versus HeJ mice (p<0.05). One significantly upregulated cluster of genes in OuJ were the heat shock proteins (Hspa1b; Hsp70), Hsp90ab1). Furthermore, O3-induced expression of HSP70 protein was increased in OuJ compared to HeJ mice following 24-48 h O3. Moreover, BAL polymorphonuclear leukocytes (PMN) and total protein were significantly reduced in response to O3 in Hspa1a/Hspa1btm1Dix (Hsp70-/-) compared to Hsp70+/+ mice (p<0.05). TLR4 signaling (MYD88-dependent), ERK1/2, AP-1 activity, and KC protein content were also significantly reduced after O3 exposure in Hsp70-/- compared to Hsp70+/+ mice (p<0.05). These studies suggest that HSP70 is involved in the regulation of O3-induced lung inflammation through the TLR4 pathway and provide evidence that HSP70 is an endogenous in vivo TLR4 ligand.
Publication Title
Identification of candidate genes downstream of TLR4 signaling after ozone exposure in mice: a role for heat-shock protein 70.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 29 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Toll like receptor 4 (TLR4), an innate immunity gene, is involved in responses to several pulmonary agonists including endotoxin (LPS; Poltorak et al.,1998), ozone (O3 ,Kleeberger et. al., 2001), Pseudomonas aeruginosa (Faure et al, 2004), and hyperoxia (Zhang et al, 2005). TLR4 appears to partially mediate the response to LPS- and O3-induced lung injury, however, TLR4 is protective for prevention of injury in Pseudomonas aeruginosa infection and against acute lung injury (hyperoxia). The mechanism behind this protection is unclear. We previously demonstrated that TLR4 was also protective against BHT-induced chronic inflammation and tumor promotion (Bauer et al, 2005). C.C3H-Tlr4Lps-d (BALBLps-d) mice, congenic for a 10 cM region of C3H/HeJ chromosome 4 that contains Tlr4 (Vogel et al, 1994), have a missence mutation that renders TLR4 dysfunctional. The Tlr4 mutation likely abrogates signaling by disrupting a direct point of contact with other signaling molecules (Akira S, Takeda K. Toll-like receptor signalling. Nat Rev Immunol 2004;4(7):499-511.). Bronchoalveolar lavage fluid (BALF) alveolar macrophages, lymphocytes, and total protein content were significantly elevated in BALBLps-d mice compared to BALB/c (BALB; Tlr4 sufficient) mice following chronic BHT (Bauer et al., 2005). BALBLps-d mice also had a significant increase in tumor multiplicity (60%) over that of BALB mice in response to an MCA/BHT tumor promotion protocol. While this was the first model to demonstrate a protective role for TLR4 in chronic lung inflammation and tumorigenesis, the downstream mechanism regulating this protective response remains unknown. Using Affymetrix microarray analysis followed by GeneSpring and Ingenuity pathway analyses, we herein identified known and novel downstream pathways and their interactions that may be involved in the protective mechanism elicited by TLR4. We therefore hypothesize that these pathways and interactions amongst the genes identified during the tumor promotion/chronic inflammation stage are in part influencing the differential strain response observed during tumorigenesis.
Publication Title
Transcriptomic analysis of pathways regulated by toll-like receptor 4 in a murine model of chronic pulmonary inflammation and carcinogenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
Illumina HiSeq 2000
Description
Ionizing radiation (IR) has long been associated with reduced hematopoietic function and increased malignancies, although the mechanisms behind this relationship remain poorly understood. The carcinogenic effect of IR has been commonly attributed to the direct induction of DNA damage. We demonstrate that IR exposure results in long-term, somatically heritable, cell-intrinsic reductions in HSC self-renewal that is mediated by C/EBPa and reversed by Notch, both of which are associated with human leukemias. Remarkably, restoration of HSC self-renewal prevents selection for C/EBPa loss of function in previously irradiated HSC pools. We propose that environmental insults prompt HSC to initiate a program limiting their self-renewal to prevent damaged HSC from contributing to hematopoiesis. This "programmed mediocrity" is advantageous for the localized insults animals have evolved to deal with, but becomes tumor promoting when the entire HSC compartment is damaged, such as during total body irradiation, by increasing selective pressure for adaptive oncogenic mutations Overall design: Examination of mRNA levels in in vitro and in vivo Hematopoietic Stem Cell that exposed to IR Ionizing radiation (IR) or control. Each group has three replicates.
Publication Title
Contrasting roles for C/EBPα and Notch in irradiation-induced multipotent hematopoietic progenitor cell defects.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 21 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
We have previously shown that some gefitinib insensitive head and neck squamous cell carcinoma (HNSCC) cell lines exhibit dominant autocrine fibroblast growth factor receptor (FGFR) signaling. Herein, we deployed a whole genome loss-of-function screen to identify genes whose knockdown potentiated the inhibitory effect of the FGFR inhibitor, AZ12908010, in HNSCC cell lines. Three HNSCC cell lines expressing a genome-wide shRNA library were treated with AZ8010 and the abundance of shRNA sequences was assessed by deep sequencing. Synthetic lethal hits were validated through use of specific inhibitors and independent shRNAs. We found that multiple alternate receptors provided protection from FGFR inhibition, including the receptor tyrosine kinases (RTKs), epidermal growth factor receptor 2 (ERBB2) and hepatocyte growth factor receptor (MET). We showed that specific knockdown of either ERBB2 or MET in combination with FGFR inhibition led to increased inhibition of growth relative to FGFR tyrosine kinase inhibitor (TKI) treatment alone. These results were confirmed using specific small molecule inhibitors of either ERBB family members or MET. Moreover, the combination of FGFR, MET and ERBB family inhibitors showed the largest inhibition of growth as compared to the double combinations. These results reveal a role for alternate RTKs in maintaining pro-growth and survival signaling in HNSCC cells in the setting of FGFR inhibition. Thus, improved therapies for HNSCC patients could involve rationally designed combinations of TKIs targeting FGFR, ERBB family members and MET. Overall design: Using a genome-wide shRNA library in combination with deep sequencing, we screened for gene targets that were synthetic lethal with the FGFR inhibitor, AZ12908010 in HNSCC cells. Three HNSCC cell lines were screened in triplicate and the abundance of shRNA sequences in drug treated cells was compared to control treated cells.
Publication Title
A receptor tyrosine kinase network composed of fibroblast growth factor receptors, epidermal growth factor receptor, v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, and hepatocyte growth factor receptor drives growth and survival of head and neck squamous carcinoma cell lines.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
A subset of our SLNs would be upregulated by Nutlin-3 and down-regulated by 5-FU and that this differential regulation could potentially explain how cell fate choice is determined
Publication Title
ATM and MET kinases are synthetic lethal with nongenotoxic activation of p53.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 34 Downloadable Samples
- Illumina HiSeq 2500
Description
RNA was sequenced from individuals Disomic and Trisomic for chromosome 21 to identify consistent changes in gene expression across individuals Overall design: Cells were cultured at subconfluency and RNA harvested for sequencing
Publication Title
Trisomy 21 consistently activates the interferon response.
Sample Metadata Fields
Sex, Age, Subject
View Samples
SRP078911- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
RNA was sequenced from Normal and DP 16 mice to identify consistent changes in gene expression across cohorts Overall design: Cells were cultured at subconfluency and RNA harvested for sequencing
Publication Title
Trisomy 21 consistently activates the interferon response.
Sample Metadata Fields
Subject
View Samples GSE28426- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Human placental development is characterized by invasion of extravillous cytotrophoblasts (EVCTs) into the uterine wall during the first trimester of pregnancy. Peroxisome proliferator-activated receptor gamma (PPARG) plays a major role in placental development, and activation of PPARG by its agonists results in inhibition of EVCT invasion in vitro. To identify PPARG target genes, microarray analysis was performed using GeneChip technology on EVCT primary cultures obtained from first-trimester human placentas. Gene expression was compared in EVCTs treated with the PPARG agonist rosiglitazone versus control. A total of 139 differentially regulated genes were identified, and changes in the expression of the following 8 genes were confirmed by reverse transcription-quantitative polymerase chain reaction: a disintegrin and metalloproteinase domain12 (ADAM12), connexin 43 (CX43), deleted in liver cancer 1 (DLC1), dipeptidyl peptidase 4 (DPP4), heme oxygenase 1 (HMOX-1), lysyl oxidase (LOX), plasminogen activator inhibitor 1 (PAI-1) and PPARG. Among the upregulated genes, lysyl oxidase (LOX) was further analyzed. In the LOX family, only LOX, LOXL1 and LOXL2 mRNA expression was significantly upregulated in rosiglitazone-treated EVCTs. RNA and protein expression of the subfamily members LOX, LOXL1 and LOXL2 were analyzed by absolute RT-qPCR and western blotting, and localized by immunohistochemistry and immunofluorescence-confocal microscopy. LOX protein was immunodetected in the EVCT cytoplasm, while LOXL1 was found in the nucleus and nucleolus. No signal was detected for LOXL2 protein. Specific inhibition of LOX activity by beta-aminopropionitrile in cell invasion assays led to an increase in EVCT invasiveness. These results suggest that LOX, LOXL1 and LOXL2 are downstream PPARG targets and that LOX activity is a negative regulator of trophoblastic cell invasion.
Publication Title
Transcriptome analysis of PPARγ target genes reveals the involvement of lysyl oxidase in human placental cytotrophoblast invasion.
Sample Metadata Fields
Specimen part, Treatment
View Samples