Volunteers were assessed at study entry, the day of the third vaccination and 24, 72 hours, two weeks after vaccination, and 5 days after challenge. 13/39 vaccinees were protected and 26/39 were not protected. Eleven vaccinees exhibited delayed onset of parasitemia. All infectivity controls developed parasitemia. Prediction Analysis of Microarrays (PAM-R) identified genes corresponding with protection. Gene Set Enrichment Analysis (GSEA) identified sets of genes associated with protection after the third immunization, before challenge.
Expression of genes associated with immunoproteasome processing of major histocompatibility complex peptides is indicative of protection with adjuvanted RTS,S malaria vaccine.
Specimen part
View SamplesAnalysis of 80 glioblastoma specimen of patients treated within clinical trials and 4 samples of "normal" brain tissue (non-tumoral). The data was used to identify factors of resistance to a chemoradiation therapy protocol of radiotherapy and concomitant and adjuvant temozolomide (alkylating agent).
Stem cell-related "self-renewal" signature and high epidermal growth factor receptor expression associated with resistance to concomitant chemoradiotherapy in glioblastoma.
Sex, Age, Specimen part, Disease, Treatment, Subject
View SamplesMicroglia play a pivotal role in the maintenance of brain homeostasis, but lose their homeostatic function during the course of neurodegenerative disorders. We identified a specific APOE-dependent molecular signature in microglia isolated from mouse models of amyotrophic lateral sclerosis, multiple sclerosis and Alzheimer’s disease (SOD1, EAE and APP-PS1) and in microglia surrounding neuritic A?-plaques in human Alzheimer’s disease brain. This is mediated by a switch from a (M0)-homeostatic to (MGnD)-neurodegenerative phenotype following phagocytosis of apoptotic neurons via the TREM2-APOE pathway. TREM2 induces APOE signaling which is a negative regulator of the transcription program in M0-homeostatic microglia. Targeting the TREM2-APOE pathway restores the M0-homeostatic signature of microglia in APP-PS1 and SOD1 mice and prevents from neuronal loss in an acute model of neurodegeneration. In SOD1 mice, TREM2 regulates MGnD in a gender-dependent manner. APOE-mediated MGnD microglia lose their tolerogenic function. Taken together, our work identifies the TREM2-APOE pathway as a major regulator of microglial functional phenotype in neurodegenerative diseases and serves as a novel target to restore homeostatic microglia. Overall design: Illumina NextSeq500 was used to identify disease-associated vs. homeostatic molecular microglia signature in microglia in different disease models and transgenic models. Bulk microglia (1,000 cells/sample) FCRLS+ sorted microglia.
The TREM2-APOE Pathway Drives the Transcriptional Phenotype of Dysfunctional Microglia in Neurodegenerative Diseases.
Specimen part, Cell line, Subject
View SamplesMicroglia play a pivotal role in the maintenance of brain homeostasis, but lose their homeostatic function during the course of neurodegenerative disorders. We identified a specific APOE-dependent molecular signature in microglia isolated from mouse models of amyotrophic lateral sclerosis, multiple sclerosis and Alzheimer’s disease (SOD1, EAE and APP-PS1) and in microglia surrounding neuritic A?-plaques in human Alzheimer’s disease brain. This is mediated by a switch from a (M0)-homeostatic to (MGnD)-neurodegenerative phenotype following phagocytosis of apoptotic neurons via the TREM2-APOE pathway. TREM2 induces APOE signaling which is a negative regulator of the transcription program in M0-homeostatic microglia. Targeting the TREM2-APOE pathway restores the M0-homeostatic signature of microglia in APP-PS1 and SOD1 mice and prevents from neuronal loss in an acute model of neurodegeneration. In SOD1 mice, TREM2 regulates MGnD in a gender-dependent manner. APOE-mediated MGnD microglia lose their tolerogenic function. Taken together, our work identifies the TREM2-APOE pathway as a major regulator of microglial functional phenotype in neurodegenerative diseases and serves as a novel target to restore homeostatic microglia. Overall design: Illumina NextSeq500 was used to identify disease-associated vs. homeostatic molecular microglia signature in microglia in different disease models and transgenic models. Bulk microglia (1,000 cells/sample) FCRLS+ sorted microglia.
The TREM2-APOE Pathway Drives the Transcriptional Phenotype of Dysfunctional Microglia in Neurodegenerative Diseases.
Sex, Specimen part, Cell line, Subject
View SamplesA microarray analysis (MA) on the F4/80+ CD11b+ macrophages (population P5) isolated from a pool of ipsilateral L4/L5 DRG in spared nerve injured WT and miR-21 cKO
Exosomal cargo including microRNA regulates sensory neuron to macrophage communication after nerve trauma.
Specimen part
View SamplesCCR6+ innate lymphoid cells were sorted from the mesenteric lymph node of nave C57BL/6 mice
Immune tolerance. Group 3 innate lymphoid cells mediate intestinal selection of commensal bacteria-specific CD4⁺ T cells.
Specimen part
View SamplesGenome-wide expression analysis of 228 hepatocellular carcinoma and 168 cirrhotic samples as part of a integrated study of gene expression and DNA-methylation de-regulation in patients with hepatocellular carcinoma
DNA methylation-based prognosis and epidrivers in hepatocellular carcinoma.
Sex, Specimen part, Disease, Subject
View Samples