A5053276768- Liver Disease Diagnosis and Treatment
- Telomeres, Telomerase, and Senescence
- Hepatitis C virus research
- Hepatitis B Virus Studies
- Immune cells in cancer
- Liver physiology and pathology
- Extracellular vesicles in disease
- Nanoplatforms for cancer theranostics
- Cancer, Lipids, and Metabolism
- Organ Transplantation Techniques and Outcomes
- Marine and fisheries research
- Hepatocellular Carcinoma Treatment and Prognosis
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Epigenetics and DNA Methylation
- Liver Disease and Transplantation
- Crustacean biology and ecology
- Advanced Nanomaterials in Catalysis
- Cancer Genomics and Diagnostics
- Single-cell and spatial transcriptomics
- Cancer Immunotherapy and Biomarkers
- Systemic Lupus Erythematosus Research
- Genomics and Chromatin Dynamics
- MicroRNA in disease regulation
- Cytomegalovirus and herpesvirus research
- Coral and Marine Ecosystems Studies
Cancer Research UK Cambridge Center
2014-2025
University of Cambridge
2015-2025
Addenbrooke's Hospital
2008-2025
Cancer Research UK
2011-2024
Hutchison/MRC Research Centre
2023-2024
Cambridge University Hospitals NHS Foundation Trust
2012-2024
Alzheimer’s Research UK
2019-2023
Robinson Brothers (United Kingdom)
2022
NIHR Cambridge Biomedical Research Centre
2020
South Australian Research and Development Institute
2008-2017
Abstract The liver has a unique ability to regenerate 1,2 ; however, in the setting of acute failure (ALF), this regenerative capacity is often overwhelmed, leaving emergency transplantation as only curative option 3–5 . Here, advance understanding human regeneration, we use paired single-nucleus RNA sequencing combined with spatial profiling healthy and ALF explant livers generate single-cell, pan-lineage atlas regeneration. We uncover novel ANXA2 + migratory hepatocyte subpopulation, which...
Abstract DNA is subject to continual damage, leaving each cell with thousands of individual lesions at any given moment 1–3 . The efficiency repair means that most known classes lesion have a half-life minutes hours 3,4 , but the extent which damage can persist for longer durations remains unknown. Here, using high-resolution phylogenetic trees from 89 donors, we identified mutations arising 818 persisted across multiple cycles in normal human stem cells blood, liver and bronchial epithelium...
The inflamed liver in chronic hepatitis B virus (HBV) infection (CHB) is characterized by a large influx of non–virus-specific CD8 T cells. Little known about the functional capacity these lymphocytes, which could provide insights into mechanisms failure viral control and damage this setting. We compared effector function total circulating intrahepatic cells CHB patients healthy donors. demonstrated that from patients, regardless their antigen specificity, were impaired ability to produce...
Hepatocytes undergo profound metabolic rewiring when primed to proliferate during compensatory regeneration and in hepatocellular carcinoma (HCC). However, the control of these processes is not fully understood. In order capture signature proliferating hepatocytes, we applied state-of-the-art systems biology approaches models liver regeneration, pharmacologically genetically activated cell proliferation, HCC.
Senescent cells trigger their own immune-mediated destruction, termed senescence surveillance. This is dependent on the inflammatory senescence-associated secretory phenotype (SASP), which includes COX2, an enzyme with complex roles in cancer. The role COX2 plays during surveillance unknown. Here, we show that RAS-induced (RIS), a critical regulator of SASP composition and vivo. regulates expression multiple components through autocrine feedback loop involving its downstream product,...
Abstract Senescence is a non-proliferative, survival state that cancer cells can enter to escape therapy. In addition soluble factors, senescence secrete extracellular vesicles (EVs), which are important mediators of intercellular communication. To explore the role senescent cell-derived EVs (senEVs) in inflammatory responses senescence, we developed an engraftment-based model wild-type mice and genetically blocked senEV release vivo, without significantly affecting mediators. SenEVs were...
Abstract Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, is a leading cause cancer-related mortality worldwide 1,2 . HCC occurs typically from background chronic disease, caused by spectrum predisposing conditions. Tumour development driven expansion clones that accumulate progressive driver mutations 3 , with hepatocytes likely cell origin 2 However, landscape in broadly independent underlying aetiologies 4 Despite an increasing range systemic treatment options...
Abstract Somatic variants accumulate in non-malignant tissues with age. Functional variants, leading to clonal advantage of hepatocytes, the liver patients acquired chronic disease (CLD). Whether somatic are common CLD from differing etiologies is unknown. We analyzed genetic alpha-1 antitrypsin (A1AT) deficiency or hemochromatosis. show that SERPINA1 , gene encoding A1AT, strongly selected for A1AT deficiency, evidence convergent evolution. Acquired clustered at carboxyl terminus...
Late survival is not improving after liver transplantation. In this study, possible reasons for were investigated.Mortality rates and causes of death ascertained in 4483 adult primary allograft recipients surviving 1 year or more from engraftment, identified through the UK Transplant Database transplanted between 1994 2007. Associations with death, cause retransplantation assessed.Mortality those beyond transplant was than twice that expected general population had improved during study...
Background and AimAlcohol-related liver disease (ALD) remains a leading cause of liver-related morbidity mortality. Age, fibrosis stage, MELD score continued alcohol consumption predict outcome in everyday clinical practice. In previous studies increased hepatocyte nuclear area expression p21, both markers senescence, were associated with stage poor non-alcohol-related fatty disease, while was related to dysfunction ALD cirrhosis. This study, therefore, investigated the pattern cell cycle...
Abstract Senescent cells interact with the surrounding microenvironment achieving diverse functional outcomes. We have recently identified that NOTCH1 can drive ‘lateral induction’ of a unique senescence phenotype in adjacent by specifically upregulating NOTCH ligand JAG1. Here we show signalling modulate chromatin structure autonomously and non-autonomously. In addition to senescence-associated heterochromatic foci (SAHF), oncogenic RAS-induced senescent (RIS) exhibit massive increase...
Abstract Radiomic image features are becoming a promising non-invasive method to obtain quantitative measurements for tumour classification and therapy response assessment in oncological research. However, despite its increasingly established application, there is need standardisation criteria further validation of feature robustness with respect imaging acquisition parameters. In this paper, the radiomic extracted from computed tomography (CT) images evaluated liver muscle, comparing values...
Senescence is a stress-responsive tumor suppressor mechanism associated with expression of the senescence-associated secretory phenotype (SASP). Through SASP, senescent cells trigger their own immune-mediated elimination, which if evaded leads to tumorigenesis. Senescent parenchymal are separated from circulating immunocytes by endothelium, targeted microenvironmental signaling. Here we show that SASP induces endothelial cell NF-κB activity and SASP-induced canonical component
INTRODUCTION: Liver cirrhosis and its complication — hepatocellular carcinoma (HCC) have been associated with increased exhaled limonene. It is currently unclear whether this increase more strongly the presence of HCC or severity liver dysfunction. METHODS: We compared breath 40 controls, 32 cirrhotic patients, 12 patients using Breath Biopsy platform. samples were analyzed by thermal desorption–gas chromatography–mass spectrometry. Limonene levels between groups correlated to bilirubin,...