Stephen E. Hamby
A5045452759- Genetic Associations and Epidemiology
- Cardiovascular Issues in Pregnancy
- Immune cells in cancer
- Phagocytosis and Immune Regulation
- Single-cell and spatial transcriptomics
- Endoplasmic Reticulum Stress and Disease
- Epigenetics and DNA Methylation
- Coronary Artery Anomalies
- Congenital heart defects research
- Telomeres, Telomerase, and Senescence
- Cardiac Valve Diseases and Treatments
- RNA modifications and cancer
- Congenital Heart Disease Studies
- Atherosclerosis and Cardiovascular Diseases
- Biomarkers in Disease Mechanisms
- Glycosylation and Glycoproteins Research
- Sarcoma Diagnosis and Treatment
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Aortic Disease and Treatment Approaches
- Cancer-related molecular mechanisms research
- Pulmonary Hypertension Research and Treatments
- RNA and protein synthesis mechanisms
- Machine Learning in Bioinformatics
- Galectins and Cancer Biology
- Enterobacteriaceae and Cronobacter Research
Glenfield Hospital
2013-2024
NIHR Leicester Biomedical Research Centre
2018-2024
University of Leicester
2014-2024
Leicester College
2022-2024
National Institute for Health Research
2015-2020
NIHR Leicester Cardiovascular Biomedical Research Unit
2014-2019
University of Lübeck
2015
University Medical Center Hamburg-Eppendorf
2015
German Centre for Cardiovascular Research
2015
Institute for Integrative and Experimental Genomics
2015
Abstract Telomeres, the end fragments of chromosomes, play key roles in cellular proliferation and senescence. Here we characterize genetic architecture naturally occurring variation leukocyte telomere length (LTL) identify causal links between LTL biomedical phenotypes 472,174 well-characterized UK Biobank participants. We identified 197 independent sentinel variants associated with at 138 genomic loci (108 new). Genetically determined differences were multiple biological traits, ranging...
Genome-wide association studies have so far identified 56 loci associated with risk of coronary artery disease (CAD). Many CAD show pleiotropy; that is, they are also other diseases or traits. This study sought to systematically test if genetic variants for non-CAD diseases/traits associate and undertake a comprehensive analysis the extent pleiotropy all loci. In discovery analyses involving 42,335 cases 78,240 control subjects we tested 29,383 common (minor allele frequency >5%) single...
The nature and underlying mechanisms of an inverse association between adult height the risk coronary artery disease (CAD) are unclear.We used a genetic approach to investigate CAD, using 180 height-associated variants. We tested change in genetically determined 1 SD (6.5 cm) with CAD 65,066 cases 128,383 controls. Using individual-level genotype data from 18,249 persons, we also examined associated presence various numbers alleles. To identify putative mechanisms, analyzed whether was known...
Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform genome-wide meta-analysis LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 regions at false dicovery rate (FDR) < 0.05 threshold prioritize genes 31, with five highlighting nucleotide metabolism as an important regulator LTL. report six significant loci in or near SENP7, MOB1B,...
Macrophages are central innate immune cells whose function declines with age. The molecular mechanisms underlying age-related changes remain poorly understood, particularly in human macrophages. We report a substantial reduction phagocytosis, migration, and chemotaxis monocyte-derived macrophages (MDMs) from older (>50 years old) compared younger (18-30 donors, alongside downregulation of transcription factors MYC USF1. In MDMs young knockdown or USF1 decreases phagocytosis alters the...
Post translational modifications (PTMs) occur in the vast majority of proteins and are essential for function. Prediction sequence location PTMs enhances functional characterisation proteins. Glycosylation is one type PTM, implicated protein folding, transport We use random forest algorithm pairwise patterns to predict glycosylation sites. identify surrounding sites an odds ratio weight their propensity association with modified residues. Our prediction program, GPP (glycosylation program),...
Background Species of Cronobacter are widespread in the environment and occasional food-borne pathogens associated with serious neonatal diseases, including bacteraemia, meningitis, necrotising enterocolitis. The genus is composed seven species: C. sakazakii, malonaticus, turicensis, dublinensis, muytjensii, universalis, condimenti. Clinical cases three species, turicensis and, particular, sakazakii multilocus sequence type 4. Thus, it plausible that virulence determinants have evolved...
Genome-wide association studies have to date identified 159 significant and suggestive loci for coronary artery disease (CAD). We now report comprehensive bioinformatics analyses of sequence variation in these predict candidate causal genes.All annotated genes the were evaluated with respect protein-coding single-nucleotide polymorphism gene expression parameters. The latter included quantitative trait loci, tissue specificity, miRNA binding. High priority further based on literature...
Adult height is associated with risk of several diseases, but the breadth such associations and whether these are primary or due to confounding unclear. We examined association adult 50 diseases spanning multiple body systems using both epidemiological genetic approaches, latter identify un-confounded possible underlying mechanisms. for (using logistic regression adjusted potential confounders) genetically determined a two-sample Mendelian randomisation approach height-associated variants as...
Spontaneous coronary artery dissection (SCAD) occurs when an epicardial is narrowed or occluded by intramural hematoma. SCAD mainly affects women and associated with pregnancy systemic arteriopathies, particularly fibromuscular dysplasia. Variants in several genes, such as those causing connective tissue disorders, have been implicated; however, the genetic architecture poorly understood. Here, we aim to better understand diagnostic yield of rare variant testing among a cohort survivors...
Spontaneous coronary artery dissection (SCAD) is a cause of acute syndrome that predominantly affects women. Its pathophysiology remains unclear but connective tissue disorders (CTD) and other vasculopathies have been observed in many SCAD patients. A genetic component for increasingly appreciated, although few genes robustly implicated. We sought to clarify the using targeted genome-wide methods cohort sporadic cases identify both common rare disease-associated variants.
Abstract Genome-wide association studies (GWAS) have identified over two hundred chromosomal loci that modulate risk of coronary artery disease (CAD). The genes affected by variants at these are largely unknown and an untapped resource to improve our understanding CAD pathophysiology identify potential therapeutic targets. Here, we prioritized 68 as the most likely causal genome-wide significant GWAS examined their regulatory roles in 286 metabolic vascular tissue gene-protein sub-networks...
Trib1 controls atherosclerotic plaque macrophage function by up-regulating OLR1, promoting foam cell formation and atherosclerosis.
Abstract Aims Fibromuscular dysplasia (FMD) and spontaneous coronary artery dissection (SCAD) are related, non-atherosclerotic arterial diseases mainly affecting middle-aged women. Little is known about their physiopathological mechanisms. We aimed to identify rare genetic causes elucidate molecular mechanisms implicated in FMD SCAD. Methods results analysed 29 exomes that included familial sporadic FMD. identified one loss-of-function variant (LoF) (frequencygnomAD = 0.000075) shared by two...
Cronobacter, formerly known as Enterobacter sakazakii, is a food-borne pathogen to cause neonatal meningitis, septicaemia and death. Current diagnostic tests for identification of Cronobacter do not differentiate between species, necessitating time consuming 16S rDNA gene sequencing or multilocus sequence typing (MLST). The organism ubiquitous, being found in the environment wide range foods, although there variation pathogenicity isolates species. Therefore be able pathogenic non-pathogenic...
Telomeres, the end fragments of chromosomes, play key roles in cellular proliferation and senescence 1 . Here we characterize genetic architecture naturally-occurring variation leucocyte telomere length (LTL) identify causal links between LTL biomedical phenotypes 472,174 well-characterized participants UK Biobank 2 We identified 197 independent sentinel variants associated with at 138 genomic loci (108 novel). Genetically-determined differences were multiple biological traits, ranging from...
Molecular mechanisms that regulate tumor-associated macrophage (TAM) phenotype and function are incompletely understood.The pseudokinase TRIB1 has been reported as a regulator of phenotypes, both in mouse human systems.Methods: Bioinformatic analysis was used to investigate the link between expression breast cancer therapeutic response chemotherapy.In vivo models included immune-competent mice characterize consequences altered (reduced or elevated) myeloid Trib1 on tumor growth composition...
Abstract Background Bicuspid aortic valve is the most common congenital valvular heart defect in general population. BAV associated with significant morbidity due to failure, formation of thoracic aneurysm, and increased risk infective endocarditis dissection. Loss function mutations NOTCH1 (OMIM 190198) has previously been disease involving valve, left ventricle outflow tract, mitral that segregates affected pedigrees as an autosomal dominant trait variable expressivity. Methods We...