A5065869694- Glioma Diagnosis and Treatment
- Cell Image Analysis Techniques
- 3D Printing in Biomedical Research
- Mathematical Biology Tumor Growth
- Pluripotent Stem Cells Research
- Advanced Fluorescence Microscopy Techniques
- Bone Tissue Engineering Materials
- Microtubule and mitosis dynamics
- Radiopharmaceutical Chemistry and Applications
- Advanced Biosensing Techniques and Applications
- biodegradable polymer synthesis and properties
- bioluminescence and chemiluminescence research
- Protein Degradation and Inhibitors
- Congenital heart defects research
- Cancer-related Molecular Pathways
- Cancer, Hypoxia, and Metabolism
- Biochemical and Molecular Research
- Collagen: Extraction and Characterization
- Ferroptosis and cancer prognosis
- Dental Implant Techniques and Outcomes
- Nanoparticle-Based Drug Delivery
- Viral Infectious Diseases and Gene Expression in Insects
- DNA Repair Mechanisms
- Periodontal Regeneration and Treatments
- Career Development and Diversity
Babraham Institute
2024
University of Cambridge
2014-2019
MRC Cancer Unit
2019
Medical Research Council
2014-2018
Hutchison/MRC Research Centre
2013-2017
The Gurdon Institute
2012
Wellcome Trust
2012
Middle East Technical University
2002-2004
Abstract Glioblastoma, the most common and aggressive adult brain tumor, is characterized by extreme phenotypic diversity treatment failure. Through fluorescence-guided resection, we identified fluorescent tissue in sub-ependymal zone (SEZ) of patients with glioblastoma. Histologic analysis genomic characterization revealed that SEZ harbors malignant cells tumor-initiating capacity, analogous to isolated from tumor mass (T). We observed resistance supramaximal chemotherapy doses along...
The G2 checkpoint monitors DNA damage, preventing mitotic entry until the damage can be resolved. mechanisms controlling recovery are unclear. Here, we identify non-genetic heterogeneity in fidelity and timing of damage-induced enforcement individual cells from same population. Single-cell fluorescence imaging reveals that damaged experience varying durations arrest, recover with levels remaining signal or damage. A gating mechanism dependent on polo-like kinase-1 (PLK1) activity underlies...
Mutations activating KRAS underlie many forms of cancer, but are refractory to therapeutic targeting. Here, we develop Poloppin, an inhibitor protein-protein interactions via the Polo-box domain (PBD) mitotic Polo-like kinases (PLKs), in monotherapeutic and combination strategies target mutant KRAS. Poloppin engages its targets biochemical cellular assays, triggering arrest with defective chromosome congression. kills cells expressing KRAS, selectively enhancing death mitosis. PLK1 or PLK4...
Fluorescence lifetime sensing enables researchers to probe the physicochemical environment of a fluorophore providing window through which we can observe complex molecular make-up cell. imaging microscopy (FLIM) quantifies and maps cell biochemistry, ensemble dynamic processes. Unfortunately, typical high-resolution FLIM systems exhibit rather limited acquisition speeds, often insufficient capture time evolution biochemical processes in living cells. Here, describe theoretical background...
Abstract Glioblastoma (GB), the most common and aggressive adult brain tumor, is characterized by phenotypic diversity ultimately treatment failure. Using fluorescence-guided sampling we integrated copy number aberration, gene expression molecular clock data to show that sub-ependymal zone (SEZ) contains precursor cells of corresponding mass. The genetically distinct tumor margin non self-renewing retain potential regenerate tumor. Functional assays confirmed SEZ marginal disease were less...
Tissue-specific stem cells are considered to have a limited differentiation potential. Recently, this notion was challenged by reports that showed broader potential of neural cells, in vitro and vivo, although the molecular mechanisms regulate plasticity unknown. Here, we report derived from mouse embryonic cortex respond Lif serum undergo epithelial mesenchymal transition (EMT)-mediated dedifferentiation process within 48 h, together with transient upregulation pluripotency markers and,...
The biochemical activities underlying cell-fate decisions vary profoundly even in genetically identical cells. But such non-genetic heterogeneity remains refractory to current imaging methods, because their capacity monitor multiple single living cells over time limited 1 . Here, we deploy a family of newly designed GFP-like sensors (NyxBits) with fast photon-counting electronics and bespoke analytics (NyxSense) multiplexed imaging, define network determining the fate exposed DNA-damaging...
SUMMARY Mutations in KRAS, particularly at codon 12, are frequent adenocarcinomas of the colon, lungs and pancreas, driving carcinogenesis by altering cell signalling reprogramming metabolism. However, specific mechanisms which different KRAS G12 alleles initiate distinctive patterns metabolic is unclear. Using isogenic panels colorectal lines harbouring G12A, G12C, G12D G12V heterozygous mutations employing transcriptomics, metabolomics, extensive biochemical validation, we demonstrate...
<div>Abstract<p>Glioblastoma, the most common and aggressive adult brain tumor, is characterized by extreme phenotypic diversity treatment failure. Through fluorescence-guided resection, we identified fluorescent tissue in sub-ependymal zone (SEZ) of patients with glioblastoma. Histologic analysis genomic characterization revealed that SEZ harbors malignant cells tumor-initiating capacity, analogous to isolated from tumor mass (T). We observed resistance supramaximal chemotherapy...
<p>Supplementary experimental procedures: this file contains an expanded materials and methods section on 5-ALA administration sample collection, cell lines propagation, immunofluorescence in vivo assays, genomic molecular clock analysis, fluorescence situ hybridization, drug concentration used the proliferation assay MGMT promoter methylation analysis. Supplementary Figure S1: figure illustrates identification of sub-ependymal zone (SEZ) two GB patients included study. S2: shows...
<p>Supplementary experimental procedures: this file contains an expanded materials and methods section on 5-ALA administration sample collection, cell lines propagation, immunofluorescence in vivo assays, genomic molecular clock analysis, fluorescence situ hybridization, drug concentration used the proliferation assay MGMT promoter methylation analysis. Supplementary Figure S1: figure illustrates identification of sub-ependymal zone (SEZ) two GB patients included study. S2: shows...
<div>Abstract<p>Glioblastoma, the most common and aggressive adult brain tumor, is characterized by extreme phenotypic diversity treatment failure. Through fluorescence-guided resection, we identified fluorescent tissue in sub-ependymal zone (SEZ) of patients with glioblastoma. Histologic analysis genomic characterization revealed that SEZ harbors malignant cells tumor-initiating capacity, analogous to isolated from tumor mass (T). We observed resistance supramaximal chemotherapy...