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GSE104509
Homo sapiens
9 Downloadable Samples
Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
JAK inhibitors like tofacitinib were thought to act primarily on T cells. However, our data and recent research suggest that JAK receptors are also present on keratinocytes. Here, we show effect of tofacitinib on primary keratinocytes, which could explain effects of topical tofacitinib treatment in psoriasis.
Publication Title
Tofacitinib Represses the Janus Kinase-Signal Transducer and Activators of Transcription Signalling Pathway in Keratinocytes.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
miR-146a acts as a negative feedback regulator of inflammation. To investigate the role of miR-146a in psoriasis psoriasiform skin inflammation was indeuced in Mir-146a-/- and wild type mice (C57BL6J) by topical applciation of imiquimod (IMQ)-cream (Aldara).
Publication Title
MicroRNA-146a suppresses IL-17-mediated skin inflammation and is genetically associated with psoriasis.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
MiR-31 is one of the most highly overexpressed miRNAs in psoriasis skin; however, its biological role in the disease has not been studied. Here we show that miR-31 is markedly overexpressed in psoriasis keratinocytes. To study the biological role of miR-31 in keratinocytes, we transfected miR-31 hairpin inhibitor (anti-miR-31) into primary human keratinocytes to inhibit endogenous miR-31. We performed a global transcriptome analysis of keratinocytes upon suppression of endogenous miR-31 using Affymetrix arrays.
Publication Title
MicroRNA-31 is overexpressed in psoriasis and modulates inflammatory cytokine and chemokine production in keratinocytes via targeting serine/threonine kinase 40.
Sample Metadata Fields
Specimen part
View Samples- Saccharomyces cerevisiae
- 7 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Investigation of global gene expression changes in Saccharomyces cerevisiae strain NRRL Y-12632 (ATCC 18824) grown in media made with asbestos mine tailings-laden water compared to the control grown in media made with double distilled water
Publication Title
Microarray data and gene expression statistics for <i>Saccharomyces cerevisiae</i> exposed to simulated asbestos mine drainage.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 10 Downloadable Samples
- Arabidopsis Gene 1.0 ST Array (aragene10st)
Description
We wanted to understand at what level BTS acts, i.e. how upstream BTS acts and if BTS misregulation affets only a subset or multiple subsets of Fe regulated genes. We studied WT and bts-3 mutant roots.
Publication Title
BRUTUS and its paralogs, BTS LIKE1 and BTS LIKE2, encode important negative regulators of the iron deficiency response in Arabidopsis thaliana.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
Illumina HiSeq 2000
Description
Melanoma resistant to MAPK inhibitors (MAPKi) displays loss of fitness upon experimental MAPKi withdrawal and, clinically, may be resensitized to MAPKi therapy after a drug holiday. Here, we uncovered and therapeutically exploited the mechanisms of MAPKi addiction in MAPKi-resistant BRAF MUT or NRAS MUT melanoma. MAPKi-addiction phenotypes evident upon drug withdrawal spanned transient cell-cycle slowdown to cell-death responses, the latter of which required a robust phosphorylated ERK (pERK) rebound. Generally, drug withdrawal–induced pERK rebound upregulated p38–FRA1–JUNB–CDKN1A and downregulated proliferation, but only a robust pERK rebound resulted in DNA damage and parthanatos-related cell death. Importantly, pharmacologically impairing DNA damage repair during MAPKi withdrawal augmented MAPKi addiction across the board by converting a cell-cycle deceleration to a caspase-dependent cell-death response or by furthering parthanatos related cell death. Specifically in MEKi-resistant NRAS MUT or atypical BRAF MUT melanoma, treatment with a type I RAF inhibitor intensified pERK rebound elicited by MEKi withdrawal, thereby promoting a cell death–predominant MAPKi-addiction phenotype. Thus, MAPKi discontinuation upon disease progression should be coupled with specific strategies that augment MAPKi addiction. Overall design: BRAF/MEK inhibitors resistant cell lines M249DDR5 and SKMEL28DDR1 were assayed for their responses after 6 hr of BRAF/MEK inhibitor treatment and after inhibitors withdrawal (by washin) for 6 and 24 hours
Publication Title
Exploiting Drug Addiction Mechanisms to Select against MAPKi-Resistant Melanoma.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HiSeq 2000, Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Non-genomic and Immune Evolution of Melanoma Acquiring MAPKi Resistance.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 169 Downloadable Samples
- IlluminaHiSeq2000
Description
Melanoma resistance to MAPK- or T cell checkpoint-targeted therapies represents a major clinical challenge, and treatment failures of MAPK-targeted therapies due to acquired resistance often require salvage immunotherapies. We show that genomic analysis of acquired resistance to MAPK inhibitors revealed key driver genes but failedto adequately account for clinical resistance. From a large-scale comparative analysis of temporal transcriptomes from patient-matched tumor biopsies, we discovered highly recurrent differential expression and signature outputs of c-MET, LEF1 and YAP1 as drivers of acquired MAPK inhibitor resistance. Moreover, integration of gene- and signature-based transcriptomic analysis revealed profound CD8 T cell deficiency detected in half of resistant melanomas in association with downregulation of dendritic cells and antigen presentation. We also propose a major methylomic basis to transcriptomic evolution under MAPK inhibitor selection. Thus, this database provides a rich informational resource, and the current landscape represents a benchmark to understanding melanoma therapeutic resistance. Overall design: Melanoma biopsies pre and post MAPKi treatment were sent for RNAseq analysis
Publication Title
Non-genomic and Immune Evolution of Melanoma Acquiring MAPKi Resistance.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
Melanoma resistance to MAPK- or T cell checkpoint-targeted therapies represents a major clinical challenge, and treatment failures of MAPK-targeted therapies due to acquired resistance often require salvage immunotherapies. We show that genomic analysis of acquired resistance to MAPK inhibitors revealed key driver genes but failedto adequately account for clinical resistance. From a large-scale comparative analysis of temporal transcriptomes from patient-matched tumor biopsies, we discovered highly recurrent differential expression and signature outputs of c-MET, LEF1 and YAP1 as drivers of acquired MAPK inhibitor resistance. Moreover, integration of gene- and signature-based transcriptomic analysis revealed profound CD8 T cell deficiency detected in half of resistant melanomas in association with downregulation of dendritic cells and antigen presentation. We also propose a major methylomic basis to transcriptomic evolution under MAPK inhibitor selection. Thus, this database provides a rich informational resource, and the current landscape represents a benchmark to understanding melanoma therapeutic resistance.
Publication Title
Non-genomic and Immune Evolution of Melanoma Acquiring MAPKi Resistance.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 32 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Anaplastic Large Cell Lymphomas (ALCL) represent a subset of lymphomas in which the Anaplastic Lymphoma Kinase (ALK) gene is frequently fused to the NPM gene. We previously demonstrated that the constitutive phosphorylation of ALK chimeric proteins is sufficient to induce cellular transformation in vitro and in vivo, and that ALK activity is strictly required for the survival of ALK positive ALCL cells. To elucidate the signaling pathways required for ALK-mediated transformation and tumor maintenance, we analyzed the transcriptomes of multiple ALK positive ALCL cell lines abrogating their ALK-mediated signaling by inducible ALK RNA interference (RNAi) or with potent and cell permeable ALK inhibitors. Transcripts derived from the gene expression profiling (GEP) analysis uncovered a reproducible signature, which included a novel group of ALK-regulated genes. Functional RNAi screening on a set of these ALK transcriptional targets revealed that the transcription factor C/EBPb and the anti-apoptotic protein BCL2A1 are absolutely necessary to induce cell transformation and/or to sustain the growth and survival of ALK positive ALCL cells. Thus, we proved that an experimentally controlled and functionally validated GEP analysis represents a powerful tool to identify novel pathogenetic networks and validate biologically suitable target genes for therapeutic interventions.
Publication Title
Functional validation of the anaplastic lymphoma kinase signature identifies CEBPB and BCL2A1 as critical target genes.
Sample Metadata Fields
No sample metadata fields
View Samples