A5002972718- Pancreatic function and diabetes
- Pluripotent Stem Cells Research
- Liver physiology and pathology
- Sexual Differentiation and Disorders
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Liver Disease Diagnosis and Treatment
- Renal and related cancers
- Long-Term Effects of COVID-19
- Diabetes and associated disorders
- Genetics and Neurodevelopmental Disorders
- Diabetes Management and Research
- Epigenetics and DNA Methylation
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Hormonal and reproductive studies
- Organ Transplantation Techniques and Outcomes
- CRISPR and Genetic Engineering
- Hormonal Regulation and Hypertension
- Congenital heart defects research
- Mesenchymal stem cell research
- Genetic Syndromes and Imprinting
- Renal Transplantation Outcomes and Treatments
- Urological Disorders and Treatments
- RNA Research and Splicing
- Genetic and Kidney Cyst Diseases
- Animal Genetics and Reproduction
University Hospitals Birmingham NHS Foundation Trust
2020-2025
University of Birmingham
2020-2025
University of Manchester
2015-2024
Manchester Academic Health Science Centre
2015-2024
Manchester University NHS Foundation Trust
2015-2024
Imperial College London
2024
Faculty (United Kingdom)
2024
University of Oxford
2022-2023
National Institute for Health Research
2016-2023
Asthma UK
2023
Human embryonic stem (hES) cells are routinely cultured under atmospheric, 20% oxygen tensions but derived from embryos which reside in a 3-5% (hypoxic) environment. Maintenance of homeostasis is critical to ensure sufficient levels for oxygen-dependent processes. This study investigates the importance specific hypoxia inducible factors (HIFs) regulating hypoxic responses hES cells. We report that culture at decreased cell proliferation and resulted significantly reduced expression SOX2,...
Hepatocyte-like cells (HLCs), differentiated from pluripotent stem by the use of soluble factors, can model human liver function and toxicity. However, at present HLC maturity whether any deficit represents a true fetal state or aberrant differentiation is unclear compounded comparison to potentially deteriorated adult hepatocytes. Therefore, we generated HLCs multiple lineages, using two different protocols, for direct with fresh
Knowledge of human pancreas development underpins our interpretation and exploitation pluripotent stem cell (PSC) differentiation toward a β-cell fate. However, almost no information exists on the early events pancreatic specification in distal foregut, bud formation, development. Here, we have studied expression profiles key lineage-specific markers to understand morphogenetic during The notochord was adjacent dorsal foregut endoderm fourth week before duodenal homeobox-1 detection. In...
Induced pluripotent stem cell derived hepatocytes (IPSC-Heps) have the potential to reduce demand for a dwindling number of primary cells used in applications ranging from therapeutic infusions vitro toxicology studies. However, current differentiation protocols and culture methods produce with reduced functionality fetal-like properties compared adult hepatocytes. We report method maturation IPSC-Heps using 3-Dimensional (3D) collagen matrices compatible high throughput screening. This...
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...
Predicting hospital length of stay (LoS) for patients with COVID-19 infection is essential to ensure that adequate bed capacity can be provided without unnecessarily restricting care other conditions. Here, we demonstrate the utility three complementary methods predicting LoS using UK national- and hospital-level data.On a national scale, relevant were identified from Hospitalisation in England Surveillance System (CHESS) reports. An Accelerated Failure Time (AFT) survival model truncation...
Rationale: Shared symptoms and genetic architecture between coronavirus disease (COVID-19) lung fibrosis suggest severe acute respiratory syndrome 2 (SARS-CoV-2) infection may lead to progressive damage. Objectives: The UK Interstitial Lung Disease Consortium (UKILD) post–COVID-19 study interim analysis was planned estimate the prevalence of residual abnormalities in people hospitalized with COVID-19 on basis risk strata. Methods: PHOSP–COVID-19 (Post-Hospitalization COVID-19) used capture...
Understanding gene expression profiles during early human pancreas development is limited by comparison to studies in rodents. In this study, from the inception of pancreatic formation, embryonic epithelial cells, approximately half which were proliferative, expressed nuclear PDX1 and cytoplasmic CK19. Later, fetal pancreas, insulin was most abundant hormone detected first trimester largely non-proliferative cells. At sequential stages development, as number insulin-positive cell clusters...
Alström syndrome is a rare autosomal recessive disorder caused by mutations in novel gene of unknown function, ALMS1. Central features include obesity, insulin resistance, and type 2 diabetes, therefore investigating ALMS1 function stands to offer new insights into the pathogenesis these common conditions. To begin this process, we have analyzed subcellular localization tissue distribution immunofluorescence. We show that widely expressed localizes centrosomes base cilia. Fibroblasts with...
Excessive secretion of aldosterone from the adrenal results in most common form endocrine hypertension. An understanding regulatory processes involved synthesis and release is needed to define biomolecular mechanisms controlling excessive production aldosterone. However, vitro studies regarding human have been limited because difficulties obtaining tissue subsequent isolation aldosterone-secreting glomerulosa cells. Herein we describe an adrenocortical carcinoma cell line, NCI-H295, which...
Dehydroepiandrosterone (DHEA) sulfotransferase, known as SULT2A1, converts the androgen precursor DHEA to its inactive sulfate ester, DHEAS [corrected], thereby preventing conversion of an active androgen. SULT2A1 requires 3'-phosphoadenosine-5'-phosphosulfate (PAPS) for catalytic activity. We have identified compound heterozygous mutations in gene encoding human PAPS synthase 2 (PAPSS2) a girl with premature pubarche, hyperandrogenic anovulation, very low levels, and increased levels. In...
Failure to predict hepatotoxic drugs in preclinical testing makes it imperative develop better liver models with a stable phenotype culture. Stem cell-derived offer promise, differentiated hepatocyte-like cells currently considered be "fetal-like" their maturity. However, this judgment is based on limited biomarkers or transcripts and lacks the required proteomic datasets that directly compare fetal adult hepatocytes. Here, we quantitatively proteomes of human liver, hepatocytes, HepG2 cell...
Appropriate development of stratified, squamous, keratinizing epithelia, such as the epidermis and oral generates an outer protective permeability barrier that prevents water loss, entry toxins, microbial invasion. During embryogenesis, immature ectoderm initially consists a single layer undifferentiated, cuboidal epithelial cells stratifies to produce flattened periderm unknown function. Here, we determined form in distinct pattern early exhibit highly polarized expression adhesion...
The molecular basis of type 2 diabetes predisposition at most established susceptibility loci remains poorly understood. KCNQ1 maps within the 11p15.5 imprinted domain, a region with an role in congenital growth phenotypes. Variants intronic to influence when maternally inherited. By use quantitative PCR and pyrosequencing human adult islet fetal pancreas samples, we investigated imprinting status regional transcripts aimed determine whether risk alleles DNA methylation gene expression....
Cytochrome P450 17alpha-hydroxylase/17-20 lyase (P450(C17)) is a critical branchpoint enzyme for steroid hormone biosynthesis. During human gestation, P450(C17) required the production of dehydroepiandrostenedione sulfate by fetal adrenal cortex and testicular androgens that mediate male sexual differentiation. In this study, we investigate regulation CYP17 gene two orphan nuclear receptors, steroidogenic factor 1 (SF-1) DAX1. embryos, SF-1 DAX1 are expressed throughout developing from its...
The regulation of biosynthesis the adrenal C19 steroids (the so-called androgens) remains unclear. Understanding production is important when benefits these are considered on processes and diseases associated with aging. In vitro studies defining mechanisms that regulate human have been limited because difficulties in obtaining tissue. A cell line retains differentiated functions would greatly facilitate research this area. Herein, we describe use adrenocortical tumor H295 as a model to...