A5080104851- Liver Disease Diagnosis and Treatment
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Liver physiology and pathology
- Liver Disease and Transplantation
- Hepatocellular Carcinoma Treatment and Prognosis
- Poetry Analysis and Criticism
- Pancreatic and Hepatic Oncology Research
- Schizophrenia research and treatment
- Ancient Egypt and Archaeology
- Pediatric Hepatobiliary Diseases and Treatments
- Gallbladder and Bile Duct Disorders
- Archaeology and Historical Studies
- Irish and British Studies
- Cancer Genomics and Diagnostics
- MicroRNA in disease regulation
- Cancer-related gene regulation
- RNA modifications and cancer
- Liver Diseases and Immunity
- Bipolar Disorder and Treatment
- Organ Transplantation Techniques and Outcomes
- Diet, Metabolism, and Disease
- Endoplasmic Reticulum Stress and Disease
- Cancer-related molecular mechanisms research
- Mental Health and Psychiatry
- French Literature and Poetry
Centre for Inflammation Research
2016-2025
University of Edinburgh
2016-2025
MRC Centre for Regenerative Medicine
2013-2025
The Queen's Medical Research Institute
2017-2023
Southampton General Hospital
2003-2023
Institute of Genetics and Cancer
2013-2023
Queen's Medical Centre
2008-2022
Edinburgh College
2022
Edinburgh Royal Infirmary
2007-2021
Film Independent
2021
Both the identity and source of rodent collagenase(s) that mediates matrix remodeling in liver fibrosis remain elusive. We have recently demonstrated an unequivocal role for scar-associated macrophages (SAMs) spontaneous resolution sought to determine whether SAMs are metalloproteinase (MMP) 13 (collagenase 3), considered be primary interstitial collagenase rodents. In this study, we demonstrate association between MMP13 expression presence regression experimental fibrosis. mmp13 gene was...
The metastatic process of colorectal cancer (CRC) is not fully understood and effective therapies are lacking. We show that activation NOTCH1 signaling in the murine intestinal epithelium leads to highly penetrant metastasis (100% metastasis; with >80% liver metastases) Kras
The failing Fontan circulation is associated with hepatic impairment. nature of this liver injury poorly defined.To establish the gross and histological changes patients relative to clinical, biochemical haemodynamic findings.Patients were retrospectively assessed for extracardiac conversion between September 2003 June 2005, according an established clinical protocol. Twelve patients, mean age 24.6 (range 15.8-43.4) years identified. duration since initial procedure was 14.1 6.9-26.4)...
Cholangiocarcinoma (CC) is typically diagnosed at an advanced stage and refractory to surgical intervention chemotherapy. Despite a global increase in the incidence of CC, little progress has been made toward development treatments for this cancer. Here we utilized human tissue; CC cell xenografts; p53-deficient transgenic mouse model; non-transgenic, chemically induced rat model that accurately reflects both inflammatory regenerative background associated with pathology. Using these...
The epidermal growth factor receptor ligand Amphiregulin has a well-documented role in the restoration of tissue homeostasis after injury; however, mechanism by which contributes to wound repair remains unknown. Here we show that functioned releasing bioactive transforming beta (TGF-β) from latent complexes via integrin-αV activation. Using acute injury models two different tissues, found inducing TGF-β activation on mesenchymal stromal cells (pericytes), induced their differentiation into...
•Primary BMDMs localised to liver and spleen within hours following intravenous injection in mice.•AAMs were highly phagocytic i.v. transfer elicited reductions necrotic area, HMGB1 translocation, hepatic neutrophil infiltration.•AAM reduced inflammatory mediators stimulated hepatocyte/endothelium proliferation injured liver.•Injection of clinical-grade human AAMs could partially recapitulate the efficacy murine immunocompetent mice. Background & AimFollowing acetaminophen (APAP) overdose,...
The progression of non-alcoholic steatohepatitis (NASH) to fibrosis and hepatocellular carcinoma (HCC) is aggravated by auto-aggressive T cells. gut-liver axis contributes NASH, but the mechanisms involved consequences for NASH-induced liver cancer remain unknown. We investigated role gastrointestinal B cells in development HCC.
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...
Liver zonation, the spatial separation of different metabolic pathways along liver sinusoids, is fundamental for proper functioning this organ, and its disruption can lead to development disorders such as hyperammonemia. Metabolic zonation involves induction β-catenin signaling around central veins, but how patterned activity established maintained unclear. Here, we show that molecule Rspondin3 specifically expressed within endothelial compartment vein. Conditional deletion Rspo3 in mice...
BEGINNINGS THE GREAT WAR ENTRE DEUX GUERRES SECOND WORLD CONTINUITIES IN MODERN POETRY 'POST-WAR' NORTHERN IRELAND
Psychosis is relatively common, with schizophrenia being the most prevalent form of psychotic disorder, affecting about seven in 1000 adults, onset typically occurring between ages 15 and 35.1 These disorders, which are characterised by distressing hallucinations delusions, disturbed behaviour, memory motivation problems, present a major personal,2 social,3 clinical,4 financial5 challenge. Moreover, poor physical health strongly associated schizophrenia, men dying 20 years earlier than...
To describe the histological features of liver in patients with a Fontan circulation.Specimens from biopsies carried out as part preoperative assessment prior to extracardiac cavopulmonary conversion an older style were examined and scored semi-quantitatively for pertinent features. support use scoring, biopsy specimens also ranked by eye severity allow correlation assigned scores.Liver 18 circulation assessed. All showed sinusoidal fibrosis. In 17 cases there was at least fibrous spur...
Cellular senescence is a mechanism that provides an irreversible barrier to cell cycle progression prevent undesired proliferation. However, under pathological circumstances, can adversely affect organ function, viability and regeneration. We have developed mouse model of biliary senescence, based on the conditional deletion Mdm2 in bile ducts control Krt19 promoter, exhibits features disease. Here we report senescent cholangiocytes induce profound alterations cellular signalling...
Liver fibrosis and cirrhosis are a consequence of Fontan physiology, determine prognosis. It is unclear whether non-invasive assessment liver pathology helpful to provide clinically relevant information. The aims this study were assess the spectrum Fontan-associated disease (FALD) usefulness methods biopsy confirmed fibrosis.Hepatic screening consecutive patients consisted blood panel, ultrasonography, elastography, contrast-enhanced magnetic resonance imaging (MRI)/computed tomography (CT)...
Intrahepatic cholangiocarcinoma is a treatment refractory malignancy with high mortality and an increasing incidence worldwide. Recent studies have observed that activation of Notch AKT signaling within mature hepatocytes able to induce the formation tumors displaying biliary lineage markers, thereby raising suggestion it hepatocytes, rather than cholangiocytes or hepatic progenitor cells represent cell origin this tumor. Here, we use cholangiocyte-lineage tracing system target p53 loss...
Bipolar disorder is a complex, recurrent, and severe mental illness that has an onset typically between 13 30 years of age lifetime prevalence 1.4%.1 It characterised by episodes mania or hypomania with elation, overactivity, disinhibited behaviour, as well depression profound loss interest motivation, often milder depressed mood in episodes. associated increased risk suicide physical illness, such ischaemic heart disease, diabetes, chronic obstructive airways pneumonia, unintentional...
Summary Background Validated diagnostic tools that are accurate, cost effective and acceptable to patients required for disease stratification monitoring in NAFLD . Aims To investigate the performance of multiparametric MRI alongside existing biomarkers assessment Methods Adult undergoing standard care liver biopsy were prospectively recruited at two UK centres underwent , blood sampling transient elastography withing 2 weeks biopsy. Non‐invasive markers compared histology as gold standard....
Abstract Mesenchymal cells expressing platelet-derived growth factor receptor beta (PDGFRβ) are known to be important in fibrosis of organs such as the liver and kidney. Here we show that PDGFRβ + contribute skeletal muscle cardiac via a mechanism depends on αv integrins. Mice which integrin is depleted protected from cardiotoxin laceration-induced angiotensin II-induced fibrosis. In addition, small-molecule inhibitor integrins attenuates fibrosis, even when pre-established, both muscle,...