Angie Fawkes
A5004233588- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- interferon and immune responses
- Long-Term Effects of COVID-19
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Diabetes and associated disorders
- Animal Virus Infections Studies
- Respiratory viral infections research
- Single-cell and spatial transcriptomics
- Genomics and Rare Diseases
- Liver Disease Diagnosis and Treatment
- Genetic Associations and Epidemiology
- Genomics and Chromatin Dynamics
- Genetic Syndromes and Imprinting
- RNA and protein synthesis mechanisms
- Acute Myeloid Leukemia Research
- Viral gastroenteritis research and epidemiology
- Molecular Biology Techniques and Applications
- COVID-19 Impact on Reproduction
- Endoplasmic Reticulum Stress and Disease
- Cancer-related molecular mechanisms research
- Ocular Oncology and Treatments
- COVID-19 and healthcare impacts
- Immunotherapy and Immune Responses
University of Edinburgh
2009-2025
Western General Hospital
2008-2024
International Severe Acute Respiratory and Emerging Infection Consortium
2023
St Mary's Hospital
2023
Wellcome Trust
2008-2019
Institute of Genetics and Cancer
2019
University of North Carolina at Chapel Hill
2019
UNC Lineberger Comprehensive Cancer Center
2019
Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with may identify mechanistic targets for therapeutic development3. Here we report results of GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study 2,244 critically ill patients COVID-19 from 208 UK intensive care units. We have identified replicated following new significant associations: on...
Abstract Epigenetic alterations may provide important insights into gene-environment interaction in inflammatory bowel disease (IBD). Here we observe epigenome-wide DNA methylation differences 240 newly-diagnosed IBD cases and 190 controls. These include 439 differentially methylated positions (DMPs) 5 regions (DMRs), which study detail using whole genome bisulphite sequencing. We replicate the top DMP ( RPS6KA2 ) DMRs VMP1, ITGB2 TXK an independent cohort. Using paired genetic epigenetic...
Inherited genetic factors can influence the severity of COVID-19, but molecular explanation underpinning a association is often unclear. Intracellular antiviral defenses inhibit replication viruses and reduce disease severity. To better understand relevant to we used interferon-stimulated gene (ISG) expression screening reveal that 2′-5′-oligoadenylate synthetase 1 (OAS1), through ribonuclease L, potently inhibits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We show common...
Clonal hematopoiesis of indeterminate potential (CHIP) increases rapidly in prevalence beyond age 60 and has been associated with increased risk for malignancy, heart disease ischemic stroke. CHIP is driven by somatic mutations hematopoietic stem progenitor cells (HSPCs). Because HSPCs often drive leukemia, we hypothesized that HSPC fitness substantially contributes to transformation from leukemia. defined as the proliferative advantage over carrying no or only neutral mutations. If...
Abstract The subset of patients who develop critical illness in Covid-19 have extensive inflammation affecting the lungs 1 and are strikingly different from other patients: immunosuppressive therapy benefits critically-ill patients, but may harm some non-critical cases. 2 Since susceptibility to life-threatening infections immune-mediated diseases both strongly heritable traits, we reasoned that host genetic variation identify mechanistic targets for therapeutic development Covid-19. 3...
ABSTRACT Detailed laboratory characterization of Escherichia coli O157 is essential to inform epidemiological investigations. This study assessed the utility whole-genome sequencing (WGS) for outbreak detection and surveillance E. O157, data were used identify discernible associations between genotypes clinical outcomes. One hundred five strains isolated over a 5-year period from human fecal samples in Lothian, Scotland, sequenced with Ion Torrent Personal Genome Machine. A total 8,721...
Abstract Background High-throughput transcriptomics has matured into a very well established and widely utilised research tool over the last two decades. Clinical datasets generated on range of different platforms continue to be deposited in public repositories provide an ever-growing, valuable resource for reanalysis. Cost tissue availability normally preclude processing samples across multiple technologies, making it challenging directly evaluate performance whether data from can reliably...
<title>Abstract</title> Feline diffuse iris melanoma (FDIM) is the most common primary ocular tumour in cats, with high metastatic potential. Greater intraocular invasion correlates increased mortality. No effective therapeutics exist for disease, partly due to a lack of known molecular targets associated aggressive behaviour. Here, we define transcriptomic landscape FDIM treatment-naïve cats using bulk RNA sequencing on laser capture microdissection and core biopsy specimens from...
Abstract Critical illness in COVID-19 is caused by inflammatory lung injury, mediated the host immune system. We and others have shown that genetic variation influences development of requiring critical care 1 or hospitalisation 2;3;4 following SARS-Co-V2 infection. The GenOMICC (Genetics Mortality Care) study recruits critically-ill cases compares their genomes with population controls order to find underlying disease mechanisms. Here, we use whole genome sequencing statistical fine mapping...
Background & AimsDNA methylation alterations may provide important insights into gene-environment interaction in cancer, aging, and complex diseases, such as inflammatory bowel disease (IBD). We aim first to determine whether the circulating DNA methylome patients requiring surgery predict Crohn's (CD) recurrence following intestinal resection; second compare seen with established CD that we had reported a series of inception cohorts.MethodsTOPPIC was placebo-controlled, randomized...
Abstract Modification of DNA resulting in 5-methylcytosine (5 mC) or 5-hydroxymethylcytosine (5hmC) has been shown to influence the local chromatin environment and affect transcription. Although recent advances next generation sequencing technology allow researchers map epigenetic modifications across genome, such experiments are often time-consuming cost prohibitive. Here we present a rapid effective method generating genome wide modification maps utilising commercially available...
Abstract We have generated whole-blood DNA methylation profiles from 18,869 Generation Scotland Scottish Family Health Study (GS) participants, resulting in, at the time of writing, largest single-cohort resource for basic biological and medical research: Methylation in (MeGS). GS is a community- family-based cohort, which recruited over 24,000 participants between 2006 2011. Comprehensive phenotype information, including detailed data on cognitive function, personality traits, mental...
Abstract Pulmonary inflammation drives critical illness in Covid-19, 1;2 creating a clinically homogeneous extreme phenotype, which we have previously shown to be highly efficient for discovery of genetic associations. 3;4 Despite the advanced stage illness, found that immunomodulatory therapies strong beneficial effects this group. 1;5 Further discoveries may identify additional therapeutic targets modulate severe disease. 6 In new data release from GenOMICC (Genetics Of Mortality Critical...
The FLG gene encodes the filaggrin protein which is essential for epidermal barrier formation and hydration. Mutations in are associated with a broad range of skin allergic diseases. This protocol used to genotype four mutations (R501X, 2282del4, R2447X S3247X) within gene.
Carbonyl reductase 1 (Cbr1), a recently discovered contributor to tissue glucocorticoid metabolism converting corticosterone 20β-dihydrocorticosterone (20β-DHB), is upregulated in adipose of obese humans and mice may contribute cardiometabolic complications obesity. This study tested the hypothesis that Cbr1-mediated influences mineralocorticoid receptor activation impacts glucose homeostasis lean states.
Abstract The prevalence of clonal haematopoiesis indeterminate potential (CHIP) in healthy individuals increases rapidly from age 60 onwards and has been associated with increased risk for malignancy, heart disease ischemic stroke. CHIP is driven by somatic mutations stem cells that are also drivers myeloid malignancies. Since often drive leukaemia, we hypothesised cell fitness substantially contributes to transformation leukaemia. Stem defined as the proliferative advantage over carrying no...
Abstract AimTo identify molecular sub-classes of endocrine-resistant breast tumours.MethodsWhole genome expression profiles 55 tumours were obtained using Illumina HT-12 BeadChip arrays. Endocrine resistance was defined as either (i) tumour increased in size during hormonal treatment or (ii) appearance local recurrence (iii) contra-lateral lesion (metastases new cancers) treatment. Most the treated patients post-menopausal. Hormonal included aromatase inhibitors (letrozole, anastrazole,...
Abstract RationalemiRNAs are a relatively recently discovered class of molecules with major implications in cellular biology, including tumorigenesis; yet little is known about their possible involvement the development endocrine resistance breast cancer. The aim this study was to identify sub-groups endocrine-resistant tumours distinctive miRNA profiles.Methods and ResultsFrozen biopsies were obtained from series 51 cancers, which either progressing primary tumours, local recurrences or...
Abstract RationaleChange in genes expression is one of the major molecular drivers tumour growth. Mechanisms controlling include transcriptional factors, mutations, aberrations gene copy number, epigenetic mechanisms and micro-RNA (miRNA) regulation. The last mechanism has been discovered recently there a need to investigate its involvement regulation endocrine resistant breast tumours.Methods ResultsTo identify regulated by miRNA tumours we collected frozen biopsies from series 51 growing...
Abstract Background: Transcriptomic analyses of clinical samples can help improve our understanding disease aetiology, drug effectiveness, assign molecular subtypes and derive prognostic signatures for decision-making. The success early microarray studies relied heavily on sample quality predominantly fresh frozen (FF) tissues to generate reliably robust data. emergence next-generation sequencing-based technologies from formalin-fixed paraffin-embedded (FFPE) provides an opportunity study...