Transcriptional profiling of Gastrocnemius Muscle in Pompe's disease
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ABSTRACT: Study identifying transcriptional differences present between C57BL/6J and B6;129-Gaatm1Rabn/J mice, or driven by Enzyme Replacement Therapy (ERT), Substrate Reduction Therapy (SRT), or Both, administered to the mutant strain. All expression profiles were assessed in bulk gastrocnemius muscle collected from 18-21 week-old mice that had been provided with chow formulated with vehicle (veh.), MZ-101 (SRT), or alglucosidase alfa 20mg/kg biweekly (ERT) for 12 weeks.
Project description:Gaucher disease type 1 is an inborn error of metabolic disease with the defective activity of the lysosomal enzyme acid b-glucosidase (GCase). Enzyme replacement/reconstitution therapy (ERT), infusions with purified recombinant GCases, is efficacious in reversing hematologic, hepatic, splenic, and bony disease manifestations in Gaucher type 1 patients. However, the tissue specific molecular events in Gaucher disease and their response to therapy are not known yet. To explore the molecular events underlying GCase treatment, we evaluated the tissue-specific gene expression profiles and molecular responses in our Gaucher disease mouse model, which were treated with two FDA approved commercially available GCases, imiglucerase (imig) and velaglucerase alfa (vela). Using microarray and mRNA-Seq techniques, differentially expressed genes (DEGs) were identified in the spleen and liver by the direct comparison of imig- vs. vela- treated mice. Among them three gene expression networks were derived from these spleens: 1) cell division/proliferation, 2) hematopoietic system and 3) inflammatory/macrophage response. Our study showed the occurrence of differential molecular pathophysiologic processes in the mice treated with imig compared with vela even though these two biosimilars had the same histological and biochemical efficacy 9V/null mice (Gaucher mouse model) were injected weekly via tail vein with 60U/kg/wk of imig or vela for 8 wks. To understand the molecular events underlying GCase treatment, we evaluated the tissue-specific gene expression profiles and molecular responses in our Gaucher disease mouse model, which were treated with two FDA approved commercially available GCases, imiglucerase (imig) and velaglucerase alfa (vela).
Project description:To test whether a genomic classifier (GC) predicts development of metastatic disease in patients treated with salvage radiation therapy (SRT) after radical prostatectomy (RP).
Project description:Spatial transcriptomic profiling was conducted on hippocampal brain sections from mice across four experimental combinations: cranial radiation therapy(RT) with Riluzole (label as Ir-Rz), cranial radiation therapy with vehicle (label as Ir-Veh), control with Riluzole (label as Ctl-Rz), and control with vehicle (label as Ctl-Veh).
Project description:The aim of the study was to investigate gene expression profiles of post-menopausal women receiving Premarin estrogen replacement therapy (ERT), compared to controls and to examine any correlations between the bacterial vaginosis (BV) status of the stubjects. This is the first study to use gene arrays to correlate changes in host expression to ERT and BV.
Project description:The clinical symptoms of Fabry disease are caused by progressive accumulation of unprocessed globotriaosylceramide metabolite within cells, inducing multiple organ damage. Enzyme replacement therapy (ERT) is the only strategy to restore enzymatic activity, but a reliable biomarker to assess treatment response does not exist. Here, we identify circulating miR-184 as a sensitive marker of response to ERT and of clinical outcome for cardiac and kidney involvement.
Project description:Gaucher disease type 1 is an inborn error of metabolic disease with the defective activity of the lysosomal enzyme acid b-glucosidase (GCase). Enzyme replacement/reconstitution therapy (ERT), infusions with purified recombinant GCases, is efficacious in reversing hematologic, hepatic, splenic, and bony disease manifestations in Gaucher type 1 patients. However, the tissue specific molecular events in Gaucher disease and their response to therapy are not known yet. To explore the molecular events underlying GCase treatment, we evaluated the tissue-specific gene expression profiles and molecular responses in our Gaucher disease mouse model, which were treated with two FDA approved commercially available GCases, imiglucerase (imig) and velaglucerase alfa (vela). Using microarray and mRNA-Seq techniques, differentially expressed genes (DEGs) were identified in the spleen and liver by the direct comparison of imig- vs. vela-treated mice. Among them three gene expression networks were derived from these spleens: 1) cell division/proliferation, 2) hematopoietic system and 3) inflammatory/macrophage response. Our study showed the occurrence of differential molecular pathophysiologic processes in the mice treated with imig compared with vela even though these two biosimilars had the same histological and biochemical efficacy 9V/null mice (Gaucher mouse model) were injected weekly via tail vein with 60U/kg/wk of imig or vela for 8 wks and were sacrificed one week after the injection for RNA isolation from different tissues like liver, lung and spleen.
Project description:Gaucher disease type 1 is an inborn error of metabolic disease with the defective activity of the lysosomal enzyme acid b-glucosidase (GCase). Enzyme replacement/reconstitution therapy (ERT), infusions with purified recombinant GCases, is efficacious in reversing hematologic, hepatic, splenic, and bony disease manifestations in Gaucher type 1 patients. However, the tissue specific molecular events in Gaucher disease and their response to therapy are not known yet. To explore the molecular events underlying GCase treatment, we evaluated the tissue-specific gene expression profiles and molecular responses in our Gaucher disease mouse model, which were treated with two FDA approved commercially available GCases, imiglucerase (imig) and velaglucerase alfa (vela). Using microarray and mRNA-Seq techniques, differentially expressed genes (DEGs) were identified in the spleen and liver by the direct comparison of imig- vs. vela-treated mice. Among them three gene expression networks were derived from these spleens: 1) cell division/proliferation, 2) hematopoietic system and 3) inflammatory/macrophage response. Our study showed the occurrence of differential molecular pathophysiologic processes in the mice treated with imig compared with vela even though these two biosimilars had the same histological and biochemical efficacy
Project description:Gaucher disease type 1 is an inborn error of metabolic disease with the defective activity of the lysosomal enzyme acid b-glucosidase (GCase). Enzyme replacement/reconstitution therapy (ERT), infusions with purified recombinant GCases, is efficacious in reversing hematologic, hepatic, splenic, and bony disease manifestations in Gaucher type 1 patients. However, the tissue specific molecular events in Gaucher disease and their response to therapy are not known yet. To explore the molecular events underlying GCase treatment, we evaluated the tissue-specific gene expression profiles and molecular responses in our Gaucher disease mouse model, which were treated with two FDA approved commercially available GCases, imiglucerase (imig) and velaglucerase alfa (vela). Using microarray and mRNA-Seq techniques, differentially expressed genes (DEGs) were identified in the spleen and liver by the direct comparison of imig- vs. vela- treated mice. Among them three gene expression networks were derived from these spleens: 1) cell division/proliferation, 2) hematopoietic system and 3) inflammatory/macrophage response. Our study showed the occurrence of differential molecular pathophysiologic processes in the mice treated with imig compared with vela even though these two biosimilars had the same histological and biochemical efficacy
Project description:Patients with treatment-refractory pancreatic cancer often succumb to widespread systemic metastases; however, the transcriptomic heterogeneity that underlies recalcitrance to therapy remains understudied, particularly in the spatial context. We constructed high-resolution spatial maps of transcriptional heterogeneity, clonal architecture and lineage plasticity using spatially resolved transcriptomics (SRT) from 13 primary cancers and 36 corresponding liver, lung, and peritoneal metastases, collected via a rapid (“warm”) autopsy program. To validate findings from our SRT dataset at single-cell resolution, we performed CosMX SMI profiling (Nanostring) on 7 samples from 3 patients, including primary and/or liver metastasis.
Project description:Spatially resolved transcriptomics (SRT) produces complex, multi-dimensional gene expression data sets at up to subcellular spatial resolution. While SRT provides powerful datasets to probe biological processes, well-designed computational tools provide the key to extracting value from SRT technology. Currently, no single piece of software facilitates the combined automated analysis, visualisation, and subsequent interaction of single or multi-section SRT data as a desktop application or in an immersive environment. Here we present VR-Omics, a freely available, SRT platform agnostic, stand-alone programme that incorporates an in-built, automated workflow to pre-process and spatially mine SRT data within a user-friendly graphical interface. Benchmarking demonstrates VR-Omics has superior capabilities for seamless end-to-end analyses of SRT data, hence making SRT data processing and mining accessible to users regardless of computational and data handling skills. Importantly, VR-Omics supports comparison between datasets generated using different spatial technologies alongside processing and analysis of multiple 2D or 3D SRT datasets provides a unique environment for biological discovery. Finally, we utilise VR-Omics to uncover the molecular mechanisms that drive the growth of rare paediatric cardiac rhabdomyomas.