A5083233221- Viral gastroenteritis research and epidemiology
- Pancreatic function and diabetes
- Animal Virus Infections Studies
- Viral Infections and Immunology Research
- Hepatitis Viruses Studies and Epidemiology
- Respiratory viral infections research
- Genetics and Neurodevelopmental Disorders
- RNA modifications and cancer
- Diabetes Treatment and Management
- Diabetes and associated disorders
- Clostridium difficile and Clostridium perfringens research
- Genomics and Chromatin Dynamics
- FOXO transcription factor regulation
- Organ Transplantation Techniques and Outcomes
- Genomics and Rare Diseases
- Cancer-related molecular mechanisms research
- Analog and Mixed-Signal Circuit Design
- Eicosanoids and Hypertension Pharmacology
- Renal Transplantation Outcomes and Treatments
- Liver Disease Diagnosis and Treatment
- Liver Disease and Transplantation
- Machine Learning in Bioinformatics
- Autophagy in Disease and Therapy
- Molecular Communication and Nanonetworks
- Hormonal and reproductive studies
Oxford Centre for Diabetes, Endocrinology and Metabolism
2019-2024
University of Oxford
2019-2024
Churchill Hospital
2020-2023
Public Health England
2014-2019
SUMMARY EuroRotaNet, a laboratory network, was established in order to determine the diversity of co-circulating rotavirus strains Europe over three or more seasons from 2006/2007 and currently includes 16 countries. This report highlights tremendous European population during years surveillance since points possible origins these including genetic reassortment interspecies transmission. Furthermore, ability network identify circulating with an incidence ⩾1% allowed identification emerging...
Background. The oral infant rotavirus vaccine, Rotarix, was introduced in England and Wales July 2013. We estimated the impact on laboratory-confirmed infections hospitalizations for all-cause acute gastroenteritis (AGE) during first year after introduction.
Identification of the genes and processes mediating genetic association signals for complex diseases represents a major challenge. As many type 2 diabetes (T2D) exert their effects through pancreatic islet-cell dysfunction, we performed genome-wide pooled CRISPR loss-of-function screen in human beta cell line. We assessed regulation insulin content as disease-relevant readout function identified 580 influencing this phenotype. Integration with genomic data provided experimental support 20...
Introduction Rotavirus vaccination with the live-attenuated monovalent (a G1P[8] human rotavirus strain) two-dose Rotarix vaccine was introduced in England July 2013. Since then, there have been significant reductions gastroenteritis incidence. Aim We assessed vaccine’s impact on genotype distribution and diversity 3 years post-vaccine introduction. Methods Epidemiological microbiological data genotyped rotavirus-positive samples between September 2006 August 2016 were supplied by...
Gastroenteritis is a common illness causing considerable morbidity and mortality worldwide. Despite improvements in detection methods, significant diagnostic gap still remains. Human bocavirus (HBoV)s, which are associated with respiratory infections, have also frequently been detected stool samples cases of gastroenteritis, tentative association between HBoVs, particular type-2 gastroenteritis has previously made. The aim this study was to determine the role HBoVs using archived DNA from...
Exome sequencing in diabetes presents a diagnostic challenge because depending on frequency, functional impact, and genomic environmental contexts, HNF1A variants can cause maturity-onset of the young (MODY), increase type 2 risk, or be benign. A correct diagnosis matters as it informs treatment, progression, family risk. We describe multi-dimensional dataset 73 missense identified exomes 12,940 individuals. Our aim was to develop an analytical framework for stratifying along phenotypic...
Inducible pluripotent stem cell–derived human β-like cells (BLCs) hold promise for both therapy and disease modeling, but their generation remains challenging functional analyses beyond transcriptomic morphological assessments remain limited. Here, we validate an approach using multicellular single-cell electrophysiological tools to evaluate function of BLCs from pioneer protocols that can be easily adapted more differentiated BLCs. The multi-electrode arrays (MEAs) measuring the...
Rotavirus is endemic in pig farms where it causes a loss production. This study the first to characterise porcine rotavirus circulating UK pigs. Samples from diarrheic pigs with enteritis obtained between 2010 and 2012 were genotyped order determine diversity of group A (GARV) wide range genotypes identified pigs: six G types (VP7); G2, G3, G4, G5, G9 G11 P (VP4); P[6], P[7], P[8], P[13], P[23], P[32]. With exception single P[8] isolate, there was less than 95% nucleotide identity sequences...
Hyperreactive platelets are commonly observed in diabetic patients indicating a potential link between glucose homeostasis and platelet reactivity. This raises the possibility that may play role regulation of metabolism. Pancreatic β cells central regulators systemic homeostasis. Here, we show factor(s) derived from stimulate activity selectively localize to vascular endothelium pancreatic islets. Both depletion ablation major adhesion or activation pathways consistently resulted impaired...
Noroviruses are a common cause of gastroenteritis worldwide, but outbreaks appear to be more in industrialized countries than developing countries, possibly reflecting differences exposure and immunity. In this study, age-stratified sera from India UK populations were analysed for the presence norovirus-genogroup II specific IgG by time resolved immunofluorescence assay relative levels antibodies two compared. Antibody higher among all age groups increased with India, whereas UK, antibody...
To describe infants with acute gastroenteritis symptoms in primary and secondary care who have the Rotarix vaccine-derived G1P[8] rotavirus strain identified their stools.This is a prospective national surveillance conducted by Public Health England (PHE). Rotavirus-positive samples from vaccine-eligible children are routinely submitted to PHE for confirmation, general practitioners requested complete questionnaire all cases. The modified Vesikari Score was used assess severity of...
Using chromatin conformation capture, we show that an enhancer cluster in the STARD10 type 2 diabetes (T2D) locus forms a defined 3-dimensional (3D) domain. A 4.1-kb region within this locus, carrying 5 T2D-associated variants, physically interacts with CTCF-binding regions and possessing strong transcriptional activity. Analysis of human islet 3D interaction maps identifies FCHSD2 gene as additional target cluster. CRISPR-Cas9-mediated deletion variant region, or associated enhancer, from...
ABSTRACT Patients with type 2 diabetes vary in their response to currently available therapeutic agents (including GLP-1 receptor agonists) leading suboptimal glycemic control and increased risk of complications. We show that human carriers hypomorphic T2D-risk alleles the gene encoding peptidyl-glycine alpha-amidating monooxygenase (PAM), as well Pam- knockout mice, display resistance vivo . Pam inactivation mice leads reduced gastric GLP-1R expression faster emptying: this persists during...
Abstract Identification of the genes and processes mediating genetic association signals for complex disease represents a major challenge. Since many type 2 diabetes exert their effects through pancreatic islet-cell dysfunction, we performed genome-wide pooled CRISPR loss-of- function screen in human beta cells. We focused on regulation insulin content as disease-relevant readout cell function. identified 580 influencing this phenotype: integration with genomic data provided experimental...
<ns4:p><ns4:bold>Background: </ns4:bold>Healthcare-associated infections represent a major threat to patient, staff and visitor safety. Identification of episodes that are likely have resulted from nosocomial transmission has important implications for infection control. Routinely collected data on ward admissions sample dates, combined with pathogen genomic information could provide useful insights. We describe novel, open-source, application visualising these data, demonstrate its utility...
Abstract Aim/Hypothesis Long non-coding RNAs (lncRNAs) are emerging as crucial regulators of beta cell development and function. Here, we investigate roles for an antisense lncRNA expressed from the Pax6 locus (annotated Pax6os1 in mice PAX6-AS1 humans) identity functionality. Methods expression was silenced MIN6 cells using siRNAs changes gene were determined by RNA sequencing or qRT-PCR. Mice inactivated human -null EndoC-βH1 cells, generated CRISPR/Cas9 technology. Human islets infected...
Abstract Background Tetraspanin‐7 (Tspan7) is an islet autoantigen involved in autoimmune type 1 diabetes and known to regulate β‐cell L‐type Ca 2+ channel activity. However, the role of Tspan7 pancreatic function not yet fully understood. Methods Histological analyses were conducted using immunostaining. Whole‐body metabolism was tested glucose tolerance test. Islet hormone secretion quantified static batch incubation or dynamic perifusion. transmembrane currents, electrical activity...
Abstract Pancreas and islet cell transplantation are used in the treatment of patients with diabetes complications. During static cold storage (SCS) ATP is depleted, by-products anaerobic respiration accumulate. Ischaemia-reperfusion injury (IRI) affects quantity viability islets it characterised by acinar necrosis, oedema, endothelial disruption (graft pancreatitis). The introduction HMPO2 liver & kidney preservation has demonstrated a significant reduction consequences IRI. was shown...
<p dir="ltr"><a href="" target="_blank">iPSC-derived human β-like cells (BLC) hold promise for both therapy and disease modelling, but their generation remains challenging functional analyses beyond transcriptomic morphological assessments remain limited. Here, we validate an approach using multicellular single cell electrophysiological tools to evaluate function of BLCs from pioneer protocols that can be easily adapted more differentiated BLCs. The Multi-Electrode Arrays (MEAs)...