A5038384580- Asthma and respiratory diseases
- IL-33, ST2, and ILC Pathways
- Melanoma and MAPK Pathways
- Cutaneous Melanoma Detection and Management
- Allergic Rhinitis and Sensitization
- Neonatal Respiratory Health Research
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Dermatology and Skin Diseases
- Genetic Associations and Epidemiology
- Respiratory viral infections research
- Pediatric health and respiratory diseases
- melanin and skin pigmentation
- Mechanisms of cancer metastasis
- Immune Cell Function and Interaction
- Protein Kinase Regulation and GTPase Signaling
- Cancer Genomics and Diagnostics
- Food Allergy and Anaphylaxis Research
- Epigenetics and DNA Methylation
- CRISPR and Genetic Engineering
- Mast cells and histamine
- Computational Drug Discovery Methods
- Cell Adhesion Molecules Research
- Smoking Behavior and Cessation
- Birth, Development, and Health
- Delphi Technique in Research
Denver Health Medical Center
2025
University of Colorado Denver
2025
Manchester Academic Health Science Centre
2014-2024
University of Manchester
2013-2024
Manchester University NHS Foundation Trust
2018-2024
Manchester Royal Infirmary
2024
National Health Service
2011-2023
NIHR Manchester Biomedical Research Centre
2022
Macquarie University
2021
The University of Sydney
2021
Exposure to ultraviolet light is a major causative factor in melanoma, although the relationship between risk and exposure complex. We hypothesized that clinical heterogeneity explained by genetically distinct types of melanoma with different susceptibility light.We compared genome-wide alterations number copies DNA mutational status BRAF N-RAS 126 melanomas from four groups which degree differs: 30 skin chronic sun-induced damage 40 without such damage; 36 palms, soles, subungual (acral)...
Melanomas on mucosal membranes, acral skin (soles, palms, and nail bed), with chronic sun-induced damage have infrequent mutations in BRAF NRAS, genes within the mitogen-activated protein (MAP) kinase pathway commonly mutated melanomas intermittently sun-exposed skin. This raises question of whether other aberrations are occurring MAP cascade melanoma types NRAS.We analyzed array comparative genomic hybridization data from 102 primary (38 mucosa, 28 skin, 18 without damage) for DNA copy...
Abstract Melanocytes require the RAS/RAF/MEK/ERK and cyclic AMP (cAMP) signaling pathways to maintain fine balance between proliferation differentiation. We have investigated how cross-talk these affects melanoma progression. show that cAMP suppresses CRAF activity in melanocytes this is essential suppress oncogenic potential of cells. As a consequence, BRAF alone responsible for MEK. However, when RAS mutated melanoma, cells switch their from CRAF. This accompanied by dysregulated...
Abstract Background Although atopic sensitization is one of the strongest risk factors for asthma, its relationship with asthma poorly understood. We hypothesize that ‘atopy’ encompasses multiple sub‐phenotypes relate to in different ways. Methods In two population‐based birth cohorts (Manchester and Isle Wight – IoW), we used a machine learning approach independently cluster children into classes an unsupervised manner, based on skin prick sIgE tests taken throughout childhood adolescence....
Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common that influence fetal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N = 28 459). We seven independent top single nucleotide polymorphisms (SNPs) (P < 1 × 10−6) birth length, which three were novel and four or near loci to be associated with height (LCORL, PTCH1, GPR126 HMGA2). The SNPs followed-up nine replication...
Rationale: Immunophenotypes of antiviral responses, and their relationship with asthma, allergy, lower respiratory tract infections, are poorly understood.Objectives: We characterized multiple cytokine responses peripheral blood mononuclear cells to rhinovirus stimulation, clinical outcomes.Methods: In a population-based birth cohort, we measured 28 cytokines after stimulation rhinovirus-16 in 307 children aged 11 years. used machine learning identify patterns related these outcomes, using...
Rationale: Pooling data from multiple cohorts and extending the time frame across childhood should minimize study-specific effects, enabling better characterization of wheezing. Objectives: To analyze wheezing patterns early to adolescence using combined five birth cohorts. Methods: We used latent class analysis derive wheeze phenotypes among 7,719 participants with complete report at periods. tested associations derived late asthma outcomes lung function, investigated uncertainty in...
The relationship between eczema, wheeze or asthma, and rhinitis is complex, epidemiology mechanisms of their comorbidities unclear.
Abstract We report that 10% of melanoma tumors and cell lines harbor mutations in the fibroblast growth factor receptor 2 (FGFR2) gene. These novel include three truncating 20 missense occurring at evolutionary conserved residues FGFR2 as well among all four FGFRs. The mutation spectrum is characteristic those induced by UV radiation. Mapping these onto known crystal structures followed vitro vivo studies show result loss function through several distinct mechanisms, including ligand binding...
Rationale: Longitudinal modeling of current wheezing identified similar phenotypes, but their characteristics often differ between studies. Objectives: We propose that a more comprehensive description wheeze may better describe trajectories than binary information on the presence/absence wheezing. Methods: derived six multidimensional variables spells from birth to adolescence (including duration, temporal sequencing, and extent persistence/recurrence). applied partition-around-medoids...
Background Environmental factors play a role in the pathogenesis of complex traits including atopic eczema (AE) and greater understanding gene-environment interactions (G*E) is needed to define pathomechanisms for disease prevention. We analysed data from 16 European studies test interaction between 24 most significant AE-associated loci identified genome-wide association 18 early-life environmental factors. tested replication using further 10 vitro modelling independently assess findings....
Given the role of vascular endothelial growth factor (VEGF) in lung development, we hypothesized that polymorphisms VEGF-A may be associated with function.The current study was designed to assess genetic variants as determinants airway function from infancy through early adulthood.Association between five single-nucleotide (SNPs) and were assessed longitudinally two unselected birth cohorts cross-sectionally among infants. Replication SNPs conducted adults children asthma. We investigated...
SNP in the vitamin D receptor (VDR) gene is associated with risk of lower respiratory infections. The influence genetic variation pathway resulting susceptibility to upper infections (URI) has not been investigated. We evaluated thirty-three eleven genes (DBP, DHCR7, RXRA, CYP2R1, CYP27B1, CYP24A1, CYP3A4, CYP27A1, LRP2, CUBN and VDR) URI 725 adults London, UK, using an additive model adjustment for potential confounders correction multiple comparisons. Significant associations this cohort...