A5007310050- Pancreatic function and diabetes
- Liver physiology and pathology
- Pluripotent Stem Cells Research
- Diabetes and associated disorders
- Genetics and Neurodevelopmental Disorders
- Liver Disease Diagnosis and Treatment
- Metabolism, Diabetes, and Cancer
- Digestive system and related health
- Esophageal Cancer Research and Treatment
- Epigenetics and DNA Methylation
- Wnt/β-catenin signaling in development and cancer
- Cancer-related gene regulation
- Pancreatic and Hepatic Oncology Research
- Diabetes Management and Research
- Tissue Engineering and Regenerative Medicine
- 3D Printing in Biomedical Research
- Esophageal and GI Pathology
- Metabolism and Genetic Disorders
- Diet, Metabolism, and Disease
- Animal Genetics and Reproduction
- Helicobacter pylori-related gastroenterology studies
- Developmental Biology and Gene Regulation
- Neuroscience and Neural Engineering
- Birth, Development, and Health
- Cancer Cells and Metastasis
University of Bath
2014-2023
University of Manchester
2014
MRC Centre for Regenerative Medicine
2012
University of Minnesota
2009
University of Edinburgh
2006
The University of Texas Medical Branch at Galveston
2005
Genomics Research Center, Academia Sinica
2005
University of Dundee
1993-1996
Ninewells Hospital
1993-1996
Newcastle University
1988-1995
Abstract Hepcidin is the principal iron regulatory hormone, controlling systemic absorption and remobilization of from intracellular stores. Recent in vivo studies have shown that hepcidin down-regulated by erythropoiesis, anemia, hypoxia, which meets need input for erythrocyte production. Erythropoietin (EPO) primary signal triggers erythropoiesis anemic hypoxic conditions. Therefore, a direct involvement EPO regulation can be hypothesized. We report here expression EPO, dose-dependent...
The use of small molecules to 'chemically direct' differentiation represents a powerful approach promote specification embryonic stem cells (ESCs) towards particular functional cell types for in regenerative medicine and pharmaceutical applications. Here, we demonstrate novel route chemically directed human ESCs (hESCs) into definitive endoderm (DE) exploiting selective small-molecule inhibitor glycogen synthase kinase 3 (GSK-3). This GSK-3 inhibitor, termed 1m, when used as the only...
Contributions of null and hypomorphic alleles Apc in mice produce both developmental pathophysiological phenotypes. To ascribe the resulting genotype-to-phenotype relationship unambiguously to Wnt/β-catenin pathway, we challenged allele combinations by genetically restricting intracellular β-catenin expression corresponding compound mutant mice. Subsequent evaluation extent Tcf4-reporter activity mouse embryo fibroblasts enabled genetic measurement signaling form an allelic series mutants....
Elevated glucocorticoids are associated with low birth weight and fetal ‘programming’ of hypertension glucose intolerance. In the present paper, we show that treatment rats dexamethasone during last week gestation reduces insulin content their pancreatic β-cells. We reproduce this effect in vitro using organ cultures mouse embryonic pancreas, it is an elevation expression transcription factor C/EBPβ (CCAAT/enhancer-binding protein β) a reduction Pdx-1 (pancreatic duodenal homeobox-1)....
Compounds 13 and 14 were evaluated against 11 PARP isoforms to reveal that both more potent isoform selective toward inhibiting tankyrases (TNKSs) than the "standard" inhibitor 1 (XAV939)5, i.e., IC50 = 100 pM vs TNKS2 6.5 μM PARP1 for 14. In cellular assays, inhibited Wnt-signaling, enhanced insulin-stimulated glucose uptake, proliferation of DLD-1 colorectal adenocarcinoma cells a greater extent 1.
Breast cancer is one of the most prevalent types cancers worldwide and yet, its pathophysiology poorly understood. Single-cell electrophysiological studies have provided evidence that membrane depolarisation implicated in proliferation metastasis breast cancer. However, metastatic cells are highly dynamic microscopic systems with complexities beyond a single-cell level. There an urgent need for technologies capable decoding intercellular signalling pathways networks control metastasis,...
Transdifferentiation is defined as the conversion of one cell type to another. It belongs a wider class transformations called metaplasias which also includes cases in stem cells tissue switch completely different cell. Numerous examples transdifferentiation exist within literature. For example, isolated striated muscle invertebrate jellyfish (Anthomedusae) has enormous potential and even functional organs (e.g. tentacles feeding organ (manubrium) can be generated in-vitro. In contrast, for...
Factors that promote pancreatic β cell growth and function are potential therapeutic targets for diabetes mellitus. In mice, genetic experiments suggest signaling cascades initiated by insulin IGFs positively regulate mass secretion. Akt S6 kinase (S6K) family members activated as part of these cascades, but how the interplay between proteins controls has not been determined. Here, we found although transgenic mice overexpressing constitutively active form Akt1 under rat promoter...
Subcellular localisation of xanthine oxidoreductase (XOR) was determined by indirect immunofluorescence using confocal microscopy in human endothelial and epithelial cell lines primary cultures umbilical vein cells. XOR diffusely distributed throughout the cytoplasm but with higher intensity perinuclear region. In non‐permeabilised cells, clearly seen to be asymmetrically located on outer surfaces, showing, many cases, a those faces apposed closely neighbouring Such specific distribution...
Hepatocytes isolated from the periportal or perivenous zones of livers fed rats were used to study long-term (14 h) and short-term (2 effects glucagon on gluconeogenesis ketogenesis. Long-term culture with (100 nM) resulted in a greater increase (P less than 0.01) cells (93 +/- 16 versus 30 14 nmol/h per mg protein; 72% 30% increase), but incubation similar stimulation two cell populations. Rates ketogenesis (acetoacetate D-3-hydroxybutyrate production) not significantly higher cultured...
The liver contains two systems for the removal of ammonia—the urea cycle and enzyme glutamine synthetase. These are expressed in a complementary fashion distinct populations hepatocytes, referred to as periportal perivenous cells. One unresolved problems hepatology has been elucidate molecular mechanisms responsible induction maintenance cellular heterogeneity ammonia detoxification. There is now potential explanation zonation synthetase based on Wnt/β-catenin pathway1. BioEssays 28:...
Pancreatic cells can be converted to hepatocytes by overexpression of C/EBPbeta (Shen, C-N, Slack, J.M.W. and Tosh, D., 2000. Molecular basis transdifferentiation pancreas liver. Nature Cell Biology 2: 879-887). This suggested that expression one or more C/EBP factors may distinguish liver in early development. We have now studied the C/EBPalpha mouse embryo show both are expressed exclusively bud not pancreatic buds. Their is identical hepatocyte nuclear factor 4 (HNF4), another key hepatic...