A5090455506- 3D Printing in Biomedical Research
- Cell Image Analysis Techniques
- Single-cell and spatial transcriptomics
- Pluripotent Stem Cells Research
- Cancer-related Molecular Pathways
- Angiogenesis and VEGF in Cancer
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Glioma Diagnosis and Treatment
- CRISPR and Genetic Engineering
- IL-33, ST2, and ILC Pathways
- Biosensors and Analytical Detection
- SARS-CoV-2 detection and testing
- Genomics and Chromatin Dynamics
- Hedgehog Signaling Pathway Studies
- Renal and related cancers
- Cellular Mechanics and Interactions
- Genomics and Rare Diseases
- Bioinformatics and Genomic Networks
- Genetic Syndromes and Imprinting
- Insect Resistance and Genetics
- Advanced Fluorescence Microscopy Techniques
- Advanced biosensing and bioanalysis techniques
- Protease and Inhibitor Mechanisms
- Biomedical Text Mining and Ontologies
King's College London
2016-2025
Oxford Biotherapeutics (United Kingdom)
2024-2025
Cell and Gene Therapy Catapult
2023-2025
Cell Therapy Catapult
2016-2023
Guy's Hospital
2014-2023
Babraham Bioscience Technologies (United Kingdom)
2023
Institute for Stem Cell Biology and Regenerative Medicine
2002-2020
European Institute of Oncology
2002-2019
London Cancer
2013
University College London
2010-2013
We report here the characterization of a mutant mouse line with specific gene trap event in Mdm4 locus. Absence expression results embryonic lethality (10.5 days postcoitum [dpc]), which was rescued by transferring mutation into Trp53-null background. Mutant embryos were characterized overall growth deficiency, anemia, improper neural tube closure, and dilation lateral ventricles. In situ analysis demonstrated increased levels p21(CIP1/Waf1) lower Cyclin E proliferating cell nuclear antigen...
Human tumors are believed to harbor a disabled p53 tumor suppressor pathway, either through direct mutation of the gene or aberrant expression proteins acting in such as p14ARF Mdm2. A role for Mdmx (or Mdm4) key negative regulator function vivo has been established. However, contribution formation remains be demonstrated. Here we show that retrovirus-mediated overexpression allows primary mouse embryonic fibroblast immortalization and leads neoplastic transformation combination with...
Glioblastoma multiforme (GBM) is the most common primary brain cancer in adults and there are few effective treatments. GBMs contain cells with molecular cellular characteristics of neural stem that drive tumour growth. Here we compare responses human glioblastoma-derived (GNS) genetically normal (NS) to a panel 160 small molecule kinase inhibitors. We used live-cell imaging high content image analysis tools identified JNJ-10198409 (J101) as an agent induces mitotic arrest at prometaphase...
The Hdmx gene product is related to the Hdm2 oncoprotein, both of which interact with and regulate p53 stability function. Like Hdm2, able inhibit transactivation; however, at variance promotes ubiquitination, nuclear export, degradation p53, increases stability. We report here (i) that overexpressed cytoplasmic recruits into nucleus (ii) blocks Hdm2-mediated export down-regulates p53-dependent transcription. Furthermore we showed inhibits ubiquitination. It appears, therefore, a regulatory...
Induced pluripotent stem cells (iPSCs) provide invaluable opportunities for future cell therapies as well studying human development, modelling diseases and discovering therapeutics. In order to realise the potential of iPSCs, it is crucial comprehensively characterise generated from large cohorts healthy diseased individuals. The iPSC initiative (HipSci) assessing a panel lines define phenotypes, dissect inter- intra-line donor variability identify its key determinant components. Here we...
Large cohorts of human induced pluripotent stem cells (iPSCs) from healthy donors are a potentially powerful tool for investigating the relationship between genetic variants and cellular behavior. Here, we integrate high content imaging cell shape, proliferation, other phenotypes with gene expression DNA sequence datasets over 100 iPSC lines. By applying dimensionality reduction approach, Probabilistic Estimation Expression Residuals (PEER), extracted factors that captured effects intrinsic...
In vitro models of postimplantation human development are valuable to the fields regenerative medicine and developmental biology. Here, we report characterization a robust in platform that enabled high-content screening multiple pluripotent stem cell (hPSC) lines for their ability undergo peri-gastrulation–like fate patterning upon bone morphogenetic protein 4 (BMP4) treatment geometrically confined colonies observed significant heterogeneity differentiation propensities along gastrulation...
Organoid-based models of murine and human innate lymphoid cell precursor (ILCP) maturation are presented. First, intestinal pulmonary organoids harnessed to demonstrate that the epithelial niche is sufficient drive tissue-specific all (ILC) groups in parallel, without requiring subset-specific cytokine supplementation. Then, more complex induced pluripotent stem (hiPSC)-based gut lung organoid used cells recapitulate ILC from a stringent systemic ILCP population, but only when...
The truncating mutations in tight junction protein 2 (TJP2) cause progressive cholestasis, liver failure, and hepatocyte carcinogenesis. Due to the lack of effective model systems, there are no targeted medications for pathology with TJP2 deficiency. We leveraged technologies patient-specific induced pluripotent stem cells (iPSC) CRISPR genome-editing, we aim establish a disease which recapitulates phenotypes patients
Abstract Induced pluripotent stem cell (iPSC) technology has enormous potential to provide improved cellular models of human disease. However, variable genetic and phenotypic characterisation many existing iPSC lines limits their use for research therapy. Here, we describe the systematic generation, genotyping phenotyping 522 open access iPSCs derived from 189 healthy male female individuals as part Human Pluripotent Stem Cells Initiative (HipSci: http://www.hipsci.org ). Our study provides...
Most image analysis pipelines rely on multiple channels per with subcellular reference points for cell segmentation. Single-channel phase-contrast images are often problematic, especially cells unfavorable morphology, such as induced pluripotent stem (iPSCs). Live imaging poses a further challenge, because of the introduction dimension time. Evaluations cannot be easily integrated other biological data sets including endpoint images. Here, we present workflow that incorporates novel...
High-throughput imaging methods can be applied to relevant cell culture models, fostering their use in research and translational applications. Improvements microscopy, computational capabilities data analysis have enabled high-throughput, high-content approaches from endpoint 2D microscopy images. Nonetheless, trade-offs acquisition, computation storage between content throughput remain, particular when cells structures are imaged 3D. Moreover, live 3D phase contrast images not often...
Endothelial cells (ECs) are heterogeneous across and within tissues, reflecting distinct, specialised functions. EC heterogeneity has been proposed to underpin plasticity independently from vessel microenvironments. However, driven by contact-dependent or short-range cell-cell crosstalk cannot be evaluated with single cell transcriptomic approaches, as spatial contextual information is lost. Nonetheless, quantification of understanding its molecular drivers key developing novel therapeutics...
Neural crest cells arise in the embryo from neural plate border and migrate throughout body, giving rise to many different tissue types such as bones cartilage of face, smooth muscles, neurons, melanocytes. While studied extensively animal models, development disease have been poorly described humans due challenges accessing embryonic tissues. In recent years, patient-derived human induced pluripotent stem (hiPSCs) become easier generate, several streamlined protocols enabled robust...
Alpha-1 antitrypsin deficiency (A1ATD) is a life-threatening condition caused by the inheritance of serpin family A member 1 "Z" genetic variant driving alpha-1 (AAT) protein misfolding in hepatocytes. There are no approved medicines for this disease.