A5045374845- Pulmonary Hypertension Research and Treatments
- Extracellular vesicles in disease
- Immune cells in cancer
- Parkinson's Disease Mechanisms and Treatments
- Diabetes and associated disorders
- Nuclear Receptors and Signaling
- MicroRNA in disease regulation
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Single-cell and spatial transcriptomics
- Cancer, Lipids, and Metabolism
- Tissue Engineering and Regenerative Medicine
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Bone health and treatments
- Eicosanoids and Hypertension Pharmacology
- interferon and immune responses
- Hormonal Regulation and Hypertension
- Cardiac Fibrosis and Remodeling
- RNA Interference and Gene Delivery
- Enzyme-mediated dye degradation
- Atherosclerosis and Cardiovascular Diseases
- Genomic variations and chromosomal abnormalities
- Conducting polymers and applications
- Skin and Cellular Biology Research
- Nerve injury and regeneration
- Nonmelanoma Skin Cancer Studies
University of Oxford
2020-2024
John Radcliffe Hospital
2022
University of Sheffield
2016-2022
Medical Research Council
1976-2013
Hammersmith Hospital
1988-2013
Imperial College London
2011
Mayo Clinic in Florida
2008-2010
Jacksonville College
2008-2010
WinnMed
2010
MRC Laboratory of Molecular Biology
1976
Copy number variation is a common polymorphic phenomenon within the human genome. Although majority of these events are non-deleterious they can also be highly pathogenic. Herein we characterize five families with parkinsonism that have been identified to harbor multiplication chromosomal 4q21 locus containing alpha-synuclein gene (SNCA).A methodological approach using fluorescent in situ hybridization and Affymetrix (Santa Clara, CA) 250K SNP microarrays was used each family identify genes...
Background: Cardiovascular risk in diabetes remains elevated despite glucose-lowering therapies. We hypothesized that hyperglycemia induces trained immunity macrophages, promoting persistent proatherogenic characteristics. Methods: Bone marrow–derived macrophages from control mice and with were grown physiological glucose (5 mmol/L) subjected to RNA sequencing (n=6), assay for transposase accessible chromatin immunoprecipitation (n=6) determination of hyperglycemia-induced immunity. marrow...
Abstract Aims Acute myocardial infarction rapidly increases blood neutrophils (<2 h). Release from bone marrow, in response to chemokine elevation, has been considered their source, but levels peak up 24 h after injury, and neutrophil elevation. This suggests that additional non-chemokine-dependent processes may be involved. Endothelial cell (EC) activation promotes the rapid (<30 min) release of extracellular vesicles (EVs), which have emerged as an important means cell–cell...
Overexpression of α-synuclein (SNCA) in families with multiplication mutations causes parkinsonism and subsequent dementia, characterized by diffuse Lewy Body disease post-mortem. Genetic variability SNCA contributes to risk idiopathic Parkinson's (PD), possibly as a result overexpression. downregulation is therefore valid therapeutic target for PD. We have identified human murine-specific siRNA molecules which reduce vitro. As proof concept, we demonstrate that direct infusion chemically...
Pulmonary arterial hypertension (PAH) is characterized by vascular cell proliferation and endothelial apoptosis. TLR3 (Toll-like receptor 3) a for double-stranded RNA has been recently implicated in protection.To study the expression role of PAH to determine whether agonist reduces pulmonary preclinical models.Lung tissue cells from patients with were investigated polymerase chain reaction, immunofluorescence, apoptosis assays. TLR3-/- TLR3+/+ mice exposed chronic hypoxia SU5416. Chronic or...
To determine whether global reduction of CD68 (cluster differentiation) macrophages impacts the development experimental pulmonary arterial hypertension (PAH) and this affects balance pro- anti-inflammatory within lung. Additionally, to there is evidence an altered macrophage polarization in patients with PAH. Approach Results: Macrophage was induced mice via doxycycline-induced CD68-driven cytotoxic diphtheria toxin A chain expression (macrophage low [MacLow] mice). Chimeric were generated...
Aldosterone is a mineralocorticoid hormone critically involved in arterial blood pressure regulation. Although pharmacological aldosterone antagonism reduces mortality and morbidity among patients with severe left-sided heart failure, the contribution of to pathobiology pulmonary hypertension (PAH) right ventricular (RV) failure not fully understood.The effects Eplerenone (0.1% Inspra® mixed chow) on vascular RV remodeling were evaluated mice (PH) caused by Sugen5416 injection concomitant...
Abstract Diabetes causes a range of complications that can affect multiple organs. Hyperglycemia is an important driver diabetes‐associated complications, mediated by biological processes such as dysfunction endothelial cells, fibrosis, and alterations in leukocyte number function. Here, we dissected the transcriptional response key cell types to hyperglycemia across tissues using single‐cell RNA sequencing (scRNA‐seq) identified conserved, well organ‐specific, changes associated with...
Abstract Pulmonary arterial hypertension (PAH) is a rare but fatal disease. Current treatments increase life expectancy have limited impact on the progressive pulmonary vascular remodelling that drives PAH. Osteoprotegerin (OPG) increased within serum and lesions of patients with idiopathic PAH mitogen migratory stimulus for artery smooth muscle cells (PASMCs). Here, we report pro-proliferative phenotype in PASMCs stimulated OPG mediated via Fas receptor treatment human antibody targeting...
The purpose of this study was to determine the core biological processes perturbed in subcutaneous adipose tissue familial combined hyperlipidemia (FCHL) patients. Annotation FCHL and control microarray datasets revealed a distinctive transcriptome, characterized by gene expression changes regulating five overlapping systems: cytoskeleton, cell adhesion extracellular matrix; vesicular trafficking; lipid homeostasis; cycle apoptosis. Expression values for cell-cycle inhibitor CDKN2B were...
Thirty-three basal cell carcinomas (BCC) were transplanted into athymic mice, and foci of tumour identified in 17 grafts recovered after intervals 2-5 months. Fifteen these xenografts contained apparently normal differentiated epithelia, considered to derive from elements within the original tumours. The level differentiation was very close corresponding xenograft BCC. Morphologically recognizable 'specialized' stroma present some but not all xenografted BCC, also containing only elements. A...
Idiopathic pulmonary arterial hypertension (IPAH) is increasingly diagnosed in elderly patients who also have an increased risk of co‐morbid atherosclerosis. Apolipoprotein E‐deficient (ApoE −/− ) mice develop atherosclerosis with severe PAH when fed a high‐fat diet (HFD) and levels endothelin (ET)‐1. ET‐1 receptor antagonists (ERAs) are used for the treatment but less known about whether ERAs beneficial We therefore examined HFD‐ApoE macitentan, dual ET A /ET B antagonist, would any effect...
<h3>Introduction</h3> Pulmonary arterial hypertension (PAH) is a rare but severe disease characterised by progressive pulmonary remodelling and right ventricular hypertrophy. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) cytokine that promotes proliferation migration of smooth muscle cells (PASMC) <i>in vitro,</i> required for PAH in animal models. However, the source TRAIL signalling pathways involved remain to be fully elucidated. <h3>Hypothesis</h3> We hypothesised...
Acute myocardial infarction rapidly increases blood neutrophils (<2 hours). Release of from bone marrow, in response to chemokine elevation, has been considered their source, but levels peak up 24 hours after injury, and neutrophil elevation. This suggests that additional non chemokine-dependent processes may be involved. Endothelial cell (EC) activation promotes the rapid (<30 minutes) release extracellular vesicles (EVs), which are enriched vascular adhesion molecule-1 (VCAM-1)...
<h3>Introduction</h3> The mechanisms regulating aberrant vascular remodelling in pulmonary arterial hypertension (PAH) are poorly understood and treatments targeted at halting or reversing this process lacking. Toll-like receptor 3 (TLR3) is a viral sensor more recently has been established as of endogenous damage signals, responding to mRNA released by damaged cells. TLR3 signalling induces pro- anti-inflammatory cytokine production regulates inflammation-associated apoptosis tyrosine...
<h3>Introduction</h3> Macrophages are proposed to play an important regulatory role in the pathogenesis of pulmonary arterial hypertension (PAH) as excessive infiltration detected around vascular lesions patients and animal models. The exact ‘causal’ for macrophages, whether their presence or absence is required remodelling seen PAH remains unclear. <h3>Objectives</h3> Using a novel inducible macrophage depletion model (<i>MacLow</i> mouse) we aimed determine macrophages associated with PAH....