A5044936333- Endoplasmic Reticulum Stress and Disease
- Autophagy in Disease and Therapy
- Prostate Cancer Treatment and Research
- RNA regulation and disease
- Cancer Genomics and Diagnostics
- Molecular Biology Techniques and Applications
- MicroRNA in disease regulation
- Virus-based gene therapy research
- CAR-T cell therapy research
- Genetic factors in colorectal cancer
- Cancer, Lipids, and Metabolism
- Computational Drug Discovery Methods
- Microtubule and mitosis dynamics
- Redox biology and oxidative stress
- Genetics and Neurodevelopmental Disorders
- Prostate Cancer Diagnosis and Treatment
- Single-cell and spatial transcriptomics
- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Folate and B Vitamins Research
- Hormonal and reproductive studies
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- Viral Infectious Diseases and Gene Expression in Insects
- Cancer Immunotherapy and Biomarkers
University of Oxford
2020-2025
Jenner Institute
2021-2023
Inserm
2017-2023
Université de Rennes
2017-2023
Nuffield Orthopaedic Centre
2023
Centre Eugène Marquis
2017-2023
John Radcliffe Hospital
2020-2023
Oncogenesis Stress Signaling
2017-2020
Abstract Defining the transition from benign to malignant tissue is fundamental improving early diagnosis of cancer 1 . Here we use a systematic approach study spatial genome integrity in situ and describe previously unidentified clonal relationships. We used spatially resolved transcriptomics 2 infer copy number variations >120,000 regions across multiple organs, tissues. demonstrate that genome-wide variation reveals distinct patterns within tumours nearby using an organ-wide focused on...
Research Article8 January 2018Open Access Transparent process Dual IRE1 RNase functions dictate glioblastoma development Stéphanie Lhomond Université de Bordeaux, France Search for more papers by this author Tony Avril INSERM U1242, "Chemistry, Oncogenesis, Stress, Signaling", Rennes 1, Rennes, Centre Lutte Contre le Cancer Eugène Marquis, Nicolas Dejeans Konstantinos Voutetakis Institute of Biology, Medicinal Chemistry & Biotechnology, NHRF, Athens, Greece Department Biochemistry University...
Inositol-requiring enzyme 1 (IRE1) is a major mediator of the unfolded protein response (UPR), which activated upon endoplasmic reticulum (ER) stress. Tumor cells experience ER stress due to adverse microenvironmental cues, overcome by relying on IRE1 signaling as an adaptive mechanism. Herein, we report discovery structurally new inhibitors identified through structural exploration its kinase domain. Characterization in vitro and cellular models showed that they inhibit sensitize...
Epithelial cancers are typically heterogeneous with primary prostate cancer being a typical example of histological and genomic variation. Prior studies tumour genetics revealed extensive inter intra-patient heterogeneity. Recent advances in machine learning have enabled the inference ground-truth single-nucleotide copy number variant status from transcript data. While these inferred SNV CNV states can be used to resolve clonal phylogenies, however, it is still unknown how faithfully...
Prostate cancer (PCa) is an androgen receptor (AR) driven, high-incidence disease significantly contributing to mortality. PCa in need of better risk stratification at diagnosis and treatment outcomes patients high metastasis. The unfolded protein response (UPR) AR-dependent process. However, the impact UPR transducer IRE1 on biology resistance has not been defined. We use diverse pre-clinical models stress describe activity multiple stages demonstrate its involvement with poor prognosis...
Inositol-requiring enzyme 1 (IRE1) is a bifunctional serine/threonine kinase and endoribonuclease that major mediator of the unfolded protein response (UPR) during endoplasmic reticulum (ER) stress. Tumour cells experience ER stress due to adverse environmental cues such as hypoxia or nutrient shortage high metabolic/protein-folding demand. To cope with those stresses, cancer utilise IRE1 signalling an adaptive mechanism. Here, we report discovery FDA-approved compounds methotrexate,...
Cyclin-dependent kinase 9 (CDK9) phosphorylates RNA polymerase II to promote productive transcription elongation. Here we show that short-term CDK9 inhibition affects the splicing of thousands mRNAs. impairs global and there is no evidence for a coordinated response between alternative overall transcriptome. Alternative feature aggressive prostate cancer (CRPC) enables generation anti-androgen resistant version ligand-independent androgen receptor, AR-v7. We results in loss AR AR-v7...
Abstract The Coalition for Epidemic Preparedness Innovations' “100‐day moonshot” aspires to launch a new vaccine within 100 days of pathogen identification, followed by large‐scale availability the “second hundred days.” Here, we describe work optimize adenoviral vector manufacturing rapid response, minimizing time clinical trial and first supply, maximizing output from available footprint. We virus seed expansion workflow that allows release trials 60 antigen sequence globally distributed...
Abstract The Coalition for Epidemic Preparedness Innovations’ ‘100-day moonshot’ aspires to launch a new vaccine within 100 days of pathogen identification. Here, we describe work optimize adenovirus vector manufacturing rapid response, by minimizing time clinical trial and first large-scale supply, maximizing the output from available footprint. We viral seed expansion workflow that allows release trials 60 antigen sequence identification, followed globally distributed sites further 40...
Abstract Epithelial cancers are typically heterogeneous with primary prostate cancer being a typical example of histological and genomic variation. Prostate is the second most common male in western industrialized countries. Prior studies tumor genetics revealed extensive inter intra-patient heterogeneity. Recent advances have enabled single-cell spatial transcriptomic profiling tissue specimens. The ability to resolve accurate phylogenies at high resolution would provide tools address...
You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology II (PD09)1 May 2024PD09-06 EXPLORING STROMAL DYNAMICS IN PROSTATE CANCER: INSIGHTS FROM SPATIAL TRANSCRIPTOMIC ANALYSES Sandy Figiel, Wencheng Yin, Mengxiao He, Renuka Teague, Thineskrishna Anbarasan, Nithesh Ranasinha, Sophia Abusamra, Reema Singh, Dimitrios Doultsinos, Ninu Poulose, Andrew Erickson, Clare Verrill, Richard Colling, Pelvender Gill, J. Bryant, Olivier Cussenot, Massimo Loda, Freddie C. Hamdy,...
You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology II (PD09)1 May 2024PD09-08 SPATIAL TRANSCRIPTOMIC CLONAL DECONVOLUTION IDENTIFIES THE 'LETHAL CLONE' IN PROSTATE CANCER AS DEFINED BY ABILITY TO METASTASIZE LYMPH NODES Wencheng Yin, Sandy Figiel, Mengxiao He, Renuka Teague, Thineskrishna Anbarasan, Nithesh Ranasinha, Reema Singh, Ninu Poulose, Dimitrios Doultsinos, Sophia Abusamra, Andrew Erickson, Massimo Loda, Clare Verrill, Richard Colling, Pelvender Gill,...
Abstract Insulin-like growth factor-1 (IGF-1) promotes prostate cancer (PCa) development and lethality, with immunosuppressive properties in other disease models. These studies investigated the tumor-intrinsic immune effects of IGF-1 PCa to understand mechanisms underlying its poor immunotherapy response. Transcriptional profiling human (DU145, 22Rv1) murine (Myc-CaP) cells revealed, through pathway enrichment, that cytokine signalling, antigen processing presentation, regulatory pathways,...
Abstract Endoplasmic Reticulum (ER) proteostasis control and the Unfolded Protein Response (UPR ER ) have been shown to contribute tumor development aggressiveness. As such, UPR sensor IRE1α (referred as IRE1 hereafter) is a major regulator of glioblastoma (GBM) an appealing therapeutic target. To document suitability antineoplastic pharmacological target, we investigated how this protein contributed GBM cell reprogramming, property involved in treatment resistance disease recurrence....
Abstract Genetic signatures have added a molecular dimension to prognostics and therapeutic decision-making. However, tumour heterogeneity in prostate cancer current sampling methods could confound accurate assessment. Based on previously published spatial transcriptomic data from multifocal cancer, we created virtual biopsy models that mimic conventional placement core size. We then analysed the gene expression of different prognostic (OncotypeDx ® , Decipher Prostadiag ) using step-wise...
Abstract Defining the transition from benign to malignant tissue is fundamental improve early diagnosis of cancer. We provide an unsupervised approach (SpatialInferCNV) study spatial genome integrity, in situ, gain molecular insight into clonal relationships. employed spatially resolved transcriptomics (Visium, 10x Genomics) infer copy number variations >120 000 regions across multiple organs, tissues and tumors, including three whole axial prostates. used this information deduce...
Abstract Background: The Unfolded Protein Response (UPR) is a key homeostatic mechanism that activated during endoplasmic reticulum (ER) stress caused by both intrinsic (genomic instability, metabolic demand) and extrinsic (chemo/radiotherapy, nutrient deprivation, hypoxia) factors. IRE1 the main UPR transducer, signalling transcription factor XBP1, Regulated Dependent Decay (RIDD) to resolve ER controlling expression of mRNA miRNAs. also regulates aspects DNA damage response (DDR)...