A5028601042- Single-cell and spatial transcriptomics
- Glioma Diagnosis and Treatment
- Cancer-related molecular mechanisms research
- Ferroptosis and cancer prognosis
- Rheumatoid Arthritis Research and Therapies
- Immune cells in cancer
- RNA modifications and cancer
- RNA Research and Splicing
- Electrochemical Analysis and Applications
- MicroRNA in disease regulation
- Immune Cell Function and Interaction
- Chronic Lymphocytic Leukemia Research
- Cell Image Analysis Techniques
- Analytical Chemistry and Sensors
- Autoimmune and Inflammatory Disorders Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Immunodeficiency and Autoimmune Disorders
- Advanced biosensing and bioanalysis techniques
- Bioinformatics and Genomic Networks
University of Leeds
2018-2025
St James's University Hospital
2021-2025
NIHR Leeds Musculoskeletal Biomedical Research Unit
2018-2020
Glioblastoma (GBM) brain tumors lacking IDH1 mutations (IDHwt) have the worst prognosis of all neoplasms. Patients receive surgery and chemoradiotherapy but almost always fatally recur.
Single-cell RNA sequencing has revolutionized our understanding of cellular heterogeneity, but routine methods require cell lysis and fail to probe the dynamic trajectories responsible for state transitions, which can only be inferred. Here, we present a nanobiopsy platform that enables injection exogenous molecules multigenerational longitudinal cytoplasmic sampling from single its progeny. The technique is based on scanning ion conductance microscopy (SICM) and, as proof concept, was...
Glioblastoma (GBM) presents a significant clinical challenge due to its aggressive nature and extensive heterogeneity. Tumour purity, the proportion of malignant cells within tumour, is an important covariate for understanding disease, having direct relevance or obscuring signal portion in molecular analyses bulk samples. However, current methods estimating tumour purity are non-specific technically demanding. Therefore, we aimed build reliable accessible estimator GBM. We developed...
Glioblastoma (GBM), the most aggressive adult brain cancer, comprises a complex tumour microenvironment (TME) with diverse cellular interactions driving progression and pathobiology. How these spatial patterns evolve treatment remains unclear. Here, we apply imaging mass cytometry to analyse protein-level changes in paired pre- post-treatment GBM samples from five patients. We find significant increase normal cells alongside reduction vascular cells. Moreover, despite minimal overall change...
Abstract Background The genetic risk associated with rheumatoid arthritis (RA) includes genes regulating DNA methylation, one of the hallmarks epigenetic re-programing, as well many T-cell genes, a strong MHC association, pointing to immunogenetic mechanisms disease triggers leading chronicity. aim our study was explore methylation in early, drug-naïve RA patients, towards better understanding early events pathogenesis. Result Monocytes, naïve and memory CD4 + T-cells were sorted from 6...
Characterizing and quantifying cell types within glioblastoma (GBM) tumors at scale will facilitate a better understanding of the association between cellular landscape tumor phenotypes or clinical correlates. We aimed to develop tool that deconvolutes immune neoplastic cells GBM microenvironment from bulk RNA sequencing data.
Abstract Background Glioblastoma (GBM) presents a significant clinical challenge due to its aggressive nature and extensive heterogeneity. Tumour purity, the proportion of malignant cells within tumour, is an important covariate for understanding disease, having direct relevance or obscuring signal portion in molecular analyses bulk samples. However, current methods estimating tumour purity are non-specific, unreliable technically demanding. Therefore, we aimed build reliable accessible...
ABSTRACT Single-cell RNA sequencing has revolutionised our understanding of cellular heterogeneity, but whether using isolated cells or more recent spatial transcriptomics approaches, these methods require isolation and lysis the cell under investigation. This provides a snapshot transcriptome from which dynamic trajectories, such as those that trigger state transitions, can only be inferred. Here, we present nanobiopsy: platform enables simultaneous labelling sampling single without killing...
Abstract The biological and clinical impact of neoplastic immune cell type ratios in the glioblastoma (GBM) tumour microenvironment is being realised. Characterising quantifying types within GBMs at scale will facilitate a better understanding association between cellular landscape phenotypes or correlates. This study aimed to develop tool that can deconvolute cells GBM from bulk RNA sequencing data. We developed an IDH wild-type (IDHwt) specific single reference dataset, four independent...
<h3>Career situation of first and presenting author</h3> Student for a master or PhD. <h3>Introduction</h3> Palindromic rheumatism (PR) is characterised by recurrent, episodic attacks articular inflammation, which resolve completely without residual joint damage. Whether PR should be considered as prodrome rheumatoid arthritis (RA) distinct syndrome remains unclear, over 70 years since described.<sup>1</sup> patients (non flare during flare) were recruited in Leeds; RA HC data was obtained...
Abstract Diffuse glioma is an aggressive brain cancer that characterized by a poor prognosis and universal resistance to therapy. The evolutionary processes behind this remain unclear. Previous studies the Glioma Longitudinal Analysis (GLASS) Consortium have indicated therapy-induced selective pressures shape genetic evolution of in stochastic manner. However, single-cell revealed malignant cells are highly plastic transition their cell state response diverse challenges, including changes...
Abstract Glioblastoma (GBM) brain tumours lacking IDH1 mutations (IDHwt) have the worst prognosis of all neoplasms. Patients receive surgery and chemoradiotherapy but almost always fatally recur. Using RNAseq data from 107 pairs pre- post-standard treatment locally recurrent IDHwt GBM tumours, we identified two responder subtypes based on therapy-driven changes in gene expression. In thirds patients a specific subset genes is up-regulated primary to recurrence (Up responders) one third same...
<h3>Introduction</h3> Palindromic rheumatism (PR) is characterised by recurrent, episodic attacks of articular inflammation, which resolve completely without residual joint damage. Whether PR should be considered as a prodrome rheumatoid arthritis (RA) or distinct syndrome remains unclear, over 70 years since first described.<sup>1</sup> <h3>Objectives</h3> This project investigates whether the pathogenesis and RA similar comparing gene expression profiles from PBMCs in PR, healthy control...
Abstract Diffuse glioma is an aggressive brain cancer that characterized by a poor prognosis and universal resistance to therapy. The evolutionary processes behind this remain unclear. Previous studies the Glioma Longitudinal Analysis (GLASS) Consortium have indicated therapy-induced selective pressures shape genetic evolution of in stochastic manner. However, single cell revealed malignant cells are highly plastic, capable changing their state response diverse challenges microenvironment....
Abstract Diffuse glioma is an aggressive brain cancer that characterized by a poor prognosis and universal resistance to therapy. The evolutionary processes behind this remain unclear. Previous studies the Glioma Longitudinal Analysis (GLASS) Consortium have indicated therapy-induced selective pressures shape genetic evolution of in stochastic manner. However, single cell revealed malignant cells are highly plastic transition their state response diverse challenges, including changes immune...