A5055043798- Epigenetics and DNA Methylation
- Telomeres, Telomerase, and Senescence
- Pancreatic function and diabetes
- Diabetes and associated disorders
- RNA modifications and cancer
- Birth, Development, and Health
- Genetic Syndromes and Imprinting
- Genetics, Aging, and Longevity in Model Organisms
- MicroRNA in disease regulation
- Computational Drug Discovery Methods
- Diabetes Management and Research
- Genetics and Neurodevelopmental Disorders
- Genetic Associations and Epidemiology
- Genomics and Phylogenetic Studies
- Child Nutrition and Water Access
- Genomics and Chromatin Dynamics
- American Constitutional Law and Politics
- Insect and Pesticide Research
- Plant and animal studies
- Insect and Arachnid Ecology and Behavior
- Cancer, Hypoxia, and Metabolism
- Microbial Natural Products and Biosynthesis
- Tracheal and airway disorders
- Protist diversity and phylogeny
- Systemic Lupus Erythematosus Research
Queen Mary University of London
2013-2024
University of California, Los Angeles
2021
University of Alabama at Birmingham
2012-2017
University of Cambridge
2010-2013
Unilever (United Kingdom)
2012-2013
University of St Andrews
2010
Case Western Reserve University
2006
University of Washington
1997-2002
Cellular Research (United States)
2000
Bradford Royal Infirmary
1991
Senescence is a cellular phenotype present in health and disease, characterized by stable cell-cycle arrest an inflammatory response called senescence-associated secretory (SASP). The SASP important influencing the behavior of neighboring cells altering microenvironment; yet, this role has been mainly attributed to soluble factors. Here, we show that both factors small extracellular vesicles (sEVs) are capable transmitting paracrine senescence nearby cells. Analysis individual internalizing...
Abstract Aging, often considered a result of random cellular damage, can be accurately estimated using DNA methylation profiles, the foundation pan-tissue epigenetic clocks. Here, we demonstrate development universal pan-mammalian clocks, 11,754 arrays from our Mammalian Methylation Consortium, which encompass 59 tissue types across 185 mammalian species. These predictive models estimate age with high accuracy ( r > 0.96). Age deviations correlate human mortality risk, mouse somatotropic...
Age-dependent associations between type 1 diabetes risk genes HLA, INS VNTR, and CTLA-4 autoantibodies to GAD65 (GADAs), ICA512/IA-2, insulin, islet cells were determined by logistic regression analysis in 971 incident patients with 702 control subjects aged 0–34 years. GADAs associated HLA-DQ2 young but not older (P = 0.009). Autoantibodies insulin negatively age < 0.0001) positively DQ8 0.03) VNTR 0.04), supporting possible immune tolerance induction. ICA512/IA-2 DQ2 0.04). Males...
Abstract The incidence of type 1 diabetes (T1D) has substantially increased over the past decade, suggesting a role for non-genetic factors such as epigenetic mechanisms in disease development. Here we present an epigenome-wide association study across 406,365 CpGs 52 monozygotic twin pairs discordant T1D three immune effector cell types. We observe substantial enrichment differentially variable CpG positions (DVPs) twins when compared with their healthy co-twins and healthy, unrelated...
There is increasing evidence that interindividual epigenetic variation an etiological factor in common human diseases. Such could be genetic or non-genetic origin, and epigenome-wide association studies (EWASs) are underway for a wide variety of diseases/phenotypes. However, performing EWAS associated with range issues not typically encountered genome-wide (GWASs), such as the tissue to analyzed. In many EWASs, it possible analyze target large numbers live humans, consequently surrogate...
In this study, two probabilistic machine-learning algorithms were compared for in silico target prediction of bioactive molecules, namely the well-established Laplacian-modified Naïve Bayes classifier (NB) and more recently introduced (to Cheminformatics) Parzen-Rosenblatt Window. Both classifiers trained conjunction with circular fingerprints on a large data set compounds extracted from ChEMBL, covering 894 human protein targets than 155,000 ligand-protein pairs. This is also provided as...
Human genetic studies have emphasised the dominant contribution of pancreatic islet dysfunction to development Type 2 Diabetes (T2D). However, limited annotation epigenome has constrained efforts define molecular mechanisms mediating the, largely regulatory, signals revealed by Genome-Wide Association Studies (GWAS). We characterised patterns chromatin accessibility (ATAC-seq, n = 17) and DNA methylation (whole-genome bisulphite sequencing, 10) in human islets, generating high-resolution...
As sex determines mammalian development, understanding the nature and developmental dynamics of sexually dimorphic transcriptome is important. To explore this, we generated 76 genome-wide RNA-seq profiles from mouse eight-cell embryos, late gestation adult livers, together with 4 ground-state pluripotent embryonic (ES) cell lines which both multiple ChIP-seq profiles. We complemented this previously published data to yield 5 snap-shots pre-implantation late-gestation placenta somatic tissue...
Mom's diet affects growth Nutrition is important during development. This appears to be true even in utero, with potential long-lasting effects on adult phenotype and disease. Epigenetic factors are prime suspects identifying the corresponding molecular mechanism because they can maintained throughout cell division. Holland et al. show mice that utero nutritional deficits influence offspring through epigenetic states at multicopy ribosomal DNA elements. effect influenced by genetic variation...
ABSTRACT Aging is often perceived as a degenerative process resulting from random accrual of cellular damage over time. Despite this, age can be accurately estimated by epigenetic clocks based on DNA methylation profiles almost any tissue the body. Since such pan-tissue have been successfully developed for several different species, we hypothesized that one build pan-mammalian measure in all mammalian species. To address generated data using 11,754 arrays, each profiling up to 36 thousand...
The capacity of the honey bee to produce three phenotypically distinct organisms (two female castes; queens and sterile workers, haploid male drones) from one genotype represents most remarkable examples developmental plasticity in any phylum. queen–worker morphological reproductive divide is environmentally controlled during post-embryonic development by differential feeding. Previous studies implicated metabolic flux acting via epigenetic regulation, particular DNA methylation microRNAs,...
Mammalian species exhibit a wide range of lifespans. To date, robust and dynamic molecular readout these lifespan differences has not yet been identified. Recent studies have established the existence ageing-associated differentially methylated positions (aDMPs) in human mouse. These are CpG sites at which DNA methylation dynamics show significant correlations with age. We hypothesise that aDMPs pan-mammalian variation among different mammalian species. A large-scale integrated analysis six...
Objectives Famine exposure in utero can ‘programme’ an individual towards type 2 diabetes and obesity later life. We sought to identify, (1) whether Bangladeshis exposed famine during developmental life are programmed obesity, (2) this programming was specific gestational or postnatal windows (3) epigenetic differences were associated with exposure. Design A historical cohort study performed as part of a wider cross-sectional survey. Exposure defined through birth date records participants...
Restricted oxygen diffusion can result in central cell necrosis engineered tissue, a problem that is exacerbated when engineering large tissue constructs for clinical application. Here we show pre-treating human mesenchymal stem cells (hMSCs) with synthetic membrane-active myoglobin-polymer-surfactant complexes provide reservoir of capable alleviating at the centre hyaline cartilage. This achieved through development new functionalization methodology based on polymer-surfactant conjugation,...
Fetal growth is determined by the feto-placental genome interacting with maternal in utero environment. Failure of this interplay leads to poor placental development and fetal restriction (FGR), which associated future metabolic disease. We investigated whether whole methylation differences existed umbilical cord blood placenta, between gestational-matched, FGR, appropriately grown (AGA) neonates. Using Infinium HumanMethylation450 BeadChip®, we found that DNA from FGR born at term (n = 19)...
Solid tumours have oxygen gradients and areas of near almost total anoxia. Hypoxia reduces sensitivity to 5-fluorouracil (5-FU)-chemotherapy for colorectal cancer (CRC). MicroRNAs (miRNAs) are hypoxia sensors were altered consistently in six CRC cell lines (colon cancer: DLD-1, HCT116 HT29; rectal HT55, SW837 VACO4S) maintained (1 0.2% oxygen) compared with normoxia (20.9%). also showed amino acid metabolism hypoxia-responsive miRNAs predicted target genes four pathways: beta-alanine;...
The mechanism of phospholipidosis is still not well understood. Numerous different mechanisms have been proposed, varying from direct inhibition the breakdown phospholipids to binding a drug compound phospholipid, preventing breakdown. We used probabilistic method, Parzen-Rosenblatt Window approach, build model ChEMBL dataset which can predict compound's structure both its primary pharmaceutical target and other targets with it forms off-target, usually weaker, interactions. Using small 182...
Traditional Chinese medicine (TCM) and Ayurveda have been used in humans for thousands of years. While the link to a particular indication has established man, mode-of-action (MOA) formulations often remains unknown. In this study, we aim understand MOA traditional using an silico target prediction algorithm, which aims predict protein targets (and hence MOAs), given chemical structure compound. Following approach were able establish several links between suggested MOAs experimental...
In mammals, DNA methylation profiles vary substantially between tissues. Recent genome-scale studies report that blood displays a highly distinctive methylomic profile from other somatic this study, we sought to understand why state is so different the one found in We whole contains approximately twice as many tissue-specific differentially methylated positions (tDMPs) than any tissue examined. Furthermore, large subset of tDMPs showed much lower levels for Surprisingly, these regions low...
DNA methylation is indispensible for normal human genome function. Currently there an increasingly large number of methylomic data being released in the public domain allowing opportunity to investigate relationships between methylome, function, and phenotypes. The Illumina450K one most popular platforms assessing with over 10,000 samples available domain. However, accessing all this requires downloading each individual experiment due inconsistent annotation, right can be a challenge. Here...
Cellular senescence is a stable arrest of proliferation and considered key component processes associated with carcinogenesis other ageing-related phenotypes. Here, we perform methylome analysis actively dividing deeply senescent normal human epithelial cells.