A5089680660- Liver Disease Diagnosis and Treatment
- Liver physiology and pathology
- Cystic Fibrosis Research Advances
- Liver Disease and Transplantation
- Hepatitis C virus research
- Genetic and Kidney Cyst Diseases
- Gastrointestinal motility and disorders
- Liver Diseases and Immunity
- Organ Transplantation Techniques and Outcomes
- Colorectal Cancer Screening and Detection
- Artificial Intelligence in Healthcare
- Hepatitis B Virus Studies
- RNA Research and Splicing
- Gastroesophageal reflux and treatments
- Renal and related cancers
- Endoplasmic Reticulum Stress and Disease
- Hemoglobinopathies and Related Disorders
- Nuclear Structure and Function
- Pancreatitis Pathology and Treatment
- Chronic Kidney Disease and Diabetes
- Drug-Induced Hepatotoxicity and Protection
- Gastric Cancer Management and Outcomes
- Diet and metabolism studies
- Abdominal vascular conditions and treatments
- Bone and Dental Protein Studies
University of Manchester
2016-2025
Manchester University NHS Foundation Trust
2016-2025
Diabetes Australia
2024
Wellcome Centre for Cell-Matrix Research
2018-2023
Manchester Academic Health Science Centre
2010-2023
Wythenshawe Hospital
2018-2023
National Health Service
2022
Manchester University
2020
Tanta University
2020
Certara (United States)
2020
Abstract Fibrosis due to extracellular matrix (ECM) secretion from myofibroblasts complicates many chronic liver diseases causing scarring and organ failure. Integrin-dependent interaction with scar ECM promotes pro-fibrotic features. However, the pathological intracellular mechanism in is not completely understood, further insight could enable therapeutic efforts reverse fibrosis. Here, we show that integrin beta-1, capable of binding alpha-11, regulates phenotype myofibroblasts. Integrin...
Osteopontin (OPN) is an important component of the extracellular matrix (ECM), which promotes liver fibrosis and has been described as a biomarker for its severity. Previously, we have demonstrated that Sex-determining region Y-box 9 (SOX9) ectopically expressed during activation hepatic stellate cells (HSC) when it responsible production type 1 collagen, causes scar formation in fibrosis. Here, demonstrate SOX9 regulates OPN. During normal development mature liver, OPN are coexpressed...
Abstract Autophagy and the unfolded protein response (UPR) both promote activation of hepatic stellate cells (HSC), however link between two stimuli remains unclear. Here we have explored role X-box binding 1 (XBP1), one three UPR effector pathways sought to establish interdependence autophagy during HSC activation. XBP1 induction accompanied culture-based ER stress induced by tunicamycin. Ectopic overexpression collagen 1-alpha expression in HSCs, which was inhibited knockdown ATG7 , a...
Research Article6 November 2017Open Access Source DataTransparent process SOX9 predicts progression toward cirrhosis in patients while its loss protects against liver fibrosis Varinder S Athwal Division of Diabetes, Endocrinology and Gastroenterology, Faculty Biology, Medicine & Health, Manchester Academic Health Science Centre, University Manchester, UK Innovation Division, Central Hospitals NHS Foundation Trust, Search for more papers by this author James Pritchett School Healthcare...
Extracellular matrix (ECM) deposition and resultant scar play a major role in the pathogenesis progression of liver fibrosis. Identifying core regulators ECM may lead to urgently needed diagnostic therapetic strategies for disease. The transcription factor Sex determining region Y box 9 (SOX9) is actively involved formation its prevalence patients with fibrosis predicts progression. In this study, transcriptomic approaches Sox9-abrogated myofibroblasts identified >30% genes regulated by SOX9...
Loss of the transcription factor SOX9 reduces experimentally induced kidney fibrosis in mice.
Current diagnostic tools are limited in their ability to diagnose cystic fibrosis liver disease (CFLD) as is often focal nature. Magnetic resonance extracellular volume quantification (MRI ECV) the may have utility CFLD a more selective assessed and can be performed using equipment readily available clinical practice on standard MRI protocol. Healthy volunteers (HV), CF participants with no (CF-noLD) cirrhosis (CF-C) aged 18 years above had ECV measured 3T Siemens scanner. An additional...
Circadian rhythm governs many aspects of liver physiology and its disruption exacerbates chronic disease. CLOCKΔ19 mice disrupted circadian spontaneously developed obesity metabolic syndrome, a phenotype that parallels the progression non-alcoholic fatty disease (NAFLD). NAFLD represents an increasing health burden with estimated incidence around 25% is associated increased risk towards inflammation, fibrosis carcinomas. Excessive extracellular matrix deposition (fibrosis) key driver...
Myofibroblasts are responsible for scarring during fibrosis. The scar propagates mechanical signals inducing a radical transformation in myofibroblast cell state and increasing profibrotic phenotype. Here, we show stress from progressive induces nuclear softening de-repression of heterochromatin. parallel loss H3K9Me3 enables permissive distinct chromatin accessibility gene regulation. Integrating profiles with RNA expression provides insight into the transcription network underlying switch...
In vitro to in vivo extrapolation (IVIVE) enables prediction of clinical outcomes related drug exposure various populations from data. Prudent IVIVE requires scalars specific the biologic characteristics system each population. This study determined experimentally for first time liver samples patients with varying degrees cirrhosis. Microsomal and cytosolic fractions were extracted 13 noncirrhotic 32 cirrhotic livers (six mild, moderate, severe, based on Child-Pugh score). Fractional protein...
Liver fibrosis is a major cause of morbidity and mortality. It characterised by excessive extracellular matrix (ECM) deposition from activated hepatic stellate cells (HSCs). Although potentially reversible, treatment remains limited. Understanding how ECM influences the pathogenesis disease may provide insight into novel therapeutic targets for disease. The protein Epimorphin (EPIM) has been implicated in tissue repair mechanisms several tissues, partially, through its ability to manipulate...
Cystic Fibrosis related liver disease (CFLD) is the 3rd largest cause of death in (CF). As advances pulmonary therapies have increased life-expectancy, CFLD has become more prevalent. Current guidelines may underdiagnose fibrosis, particularly its early stages. Newer modalities for assessment fibrosis provide a accurate assessment. FibroScan validated assessing several aetiologies including alcohol and fatty liver, cohort an entirely different phenotype so cut off values are not...
Abstract Rome IV bowel disorders of gut brain interaction (DGBI) and non-alcoholic fatty liver disease (NAFLD) are highly prevalent entities with overlapping pathophysiology risk factors. We aimed to evaluate the prevalence burden irritable syndrome (IBS) in patients NAFLD. Patients diagnosed NAFLD were recruited from a specialist clinic. All participants completed assessments determine fibrosis severity, including stiffness measurement (LSM), diagnostic questionnaire for interaction, IBS...