A5050716279- Tissue Engineering and Regenerative Medicine
- Advanced MRI Techniques and Applications
- Cardiovascular Function and Risk Factors
- Electrospun Nanofibers in Biomedical Applications
- Adipose Tissue and Metabolism
- Mesenchymal stem cell research
- Cancer, Hypoxia, and Metabolism
- Congenital heart defects research
- Pluripotent Stem Cells Research
- Advanced NMR Techniques and Applications
- Mitochondrial Function and Pathology
- Cardiomyopathy and Myosin Studies
- Cardiac Imaging and Diagnostics
- Cardiac Fibrosis and Remodeling
- Electron Spin Resonance Studies
- Cardiac Ischemia and Reperfusion
- 3D Printing in Biomedical Research
- Muscle Physiology and Disorders
- Cardiovascular Disease and Adiposity
- Metabolism, Diabetes, and Cancer
- RNA Interference and Gene Delivery
- Viral Infections and Immunology Research
- Pulmonary Hypertension Research and Treatments
- Pancreatic function and diabetes
- Cardiac Structural Anomalies and Repair
University of Oxford
2016-2025
Moffitt Cancer Center
2024-2025
British Cardiovascular Society
2024
British Heart Foundation
2019
University of Toronto
2018
Radboud University Nijmegen
2016
Radboud University Medical Center
2016
University College London
1997-2014
University of Cambridge
2014
Pediatrics and Genetics
2014
Myocardial infarction (MI) arising from obstruction of the coronary circulation engenders massive cardiomyocyte loss and replacement by non-contractile scar tissue, leading to pathological remodeling, dysfunction, ultimately heart failure. This is presently a global health problem for which there no effective cure. Following MI, innate immune system directs phagocytosis dead cell debris in an effort stimulate repopulation tissue renewal. In mammalian adult heart, however, persistent influx...
Significance The iron-exporting protein ferroportin is recognized as central to systemic iron regulation, but its role in tissues other than those involved handling unknown. This study shows that expression cardiomyocytes essential intracellular homeostasis and normal cardiac function. It also demonstrates the site of accumulation iron-overloaded heart depends on whether expressed cardiomyocytes. further functional significance overload highly dependent upon accumulation. These findings...
Compartmentalized cAMP/PKA signalling is now recognized as important for physiology and pathophysiology, yet a detailed understanding of the properties, regulation function local signals lacking. Here we present fluorescence resonance energy transfer (FRET)-based sensor, CUTie, which detects compartmentalized cAMP with unprecedented accuracy. targeted to specific multiprotein complexes at discrete plasmalemmal, sarcoplasmic reticular myofilament sites, reveals differential kinetics...
To study the pathogenesis of diabetic cardiomyopathy, reliable animal models type 2 diabetes are required. Physiologically relevant rodent needed, which not only replicate human pathology but also mimic disease process. Here we characterised cardiac metabolic abnormalities, and investigated optimal experimental approach for inducing disease, in a new model diabetes.Male Wistar rats were fed high-fat diet three weeks, with single intraperitoneal injection low dose streptozotocin (STZ) after...
Although diabetic cardiomyopathy is widely recognized, there are no specific treatments available. Altered myocardial substrate selection has emerged as a candidate mechanism behind the development of cardiac dysfunction in diabetes. As pyruvate dehydrogenase (PDH) activity appears central to balance use, we aimed investigate relationship between PDH flux and function rodent model type 2 diabetes explore whether or not increasing flux, with dichloroacetate, would restore use improve...
Stem cells offer a promising approach to the treatment of myocardial infarction and prevention heart failure. We have used iron labeling bone marrow stromal (BMSCs) noninvasively track cell location in infarcted rat over 16 weeks using cine-magnetic resonance imaging (cine-MRI) isolate BMSCs from grafted hearts magnetic properties donor cells. were isolated marrow, characterized by flow cytometry, transduced with lentiviral vectors expressing green fluorescent protein (GFP), labeled...
Induced pluripotent stem (iPS) cells are being used increasingly to complement their embryonic counterparts understand and develop the therapeutic potential of cells. Our objectives were identify an efficient cardiac differentiation protocol for human iPS as monolayers, demonstrate that resulting progenitors could provide a benefit in rodent model myocardial infarction. Herein, we describe 14-day monolayer, which routinely yielded mixed population over 50% cardiomyocytes, endothelium, or...
Endogenous cardiac progenitor cells, expanded from explants via cardiosphere formation, present a promising cell source to prevent heart failure following myocardial infarction. Here we used cine-magnetic resonance imaging (MRI) track administered cardiosphere-derived cells (CDCs) and measure changes in function over four months the infarcted rat heart.CDCs, cultured neonatal heart, comprised heterogeneous population including expressing mesenchymal markers CD90 CD105, stem marker c-kit...
Aims The mdx mouse has proven to be useful in understanding the cardiomyopathy that frequently occurs muscular dystrophy patients. Here we employed a comprehensive array of clinically relevant vivo MRI techniques identify early markers cardiac dysfunction and follow disease progression hearts mice. Methods Results Serial measurements morphology function were made same group mice controls (housed non-SPF facility) using at 1, 3, 6, 9 12 months after birth. Left ventricular (LV) right (RV)...
Purpose Butyrate, a short chain fatty acid, was studied as novel hyperpolarized substrate for use in dynamic nuclear polarization enhanced magnetic resonance spectroscopy experiments, to define the pathways of acid and ketone body metabolism real time. Methods Butyrate polarized via process subsequently dissolved generate an injectable metabolic substrate. Metabolism initially assessed isolated perfused rat heart, followed by evaluation vivo heart. Results Hyperpolarized butyrate generated...
Rationale: Current cardiovascular clinical imaging techniques offer only limited assessment of innate immune cell-driven inflammation, which is a potential therapeutic target in myocardial infarction (MI) and other diseases. Hyperpolarized magnetic resonance (MR) an emerging technology that generates contrast agents with 10- to 20 000-fold improvements MR signal, enabling cardiac metabolite mapping. Objective: To determine whether hyperpolarized using [1- 13 C]pyruvate can assess the local...
Significance Pulmonary arterial hypertension (PAH) is a disease in which lung blood pressure raised chronically, causing right heart failure. It has been shown that iron deficiency also raises pressure. However, we don’t know the mechanisms because understand precisely how cells of vessels are affected by levels. The smooth muscle important for controlling Our study shows specifically within these sufficient to cause PAH, even against background normal levels other tissues.
The role of peroxisome proliferator-activated receptor α (PPARα)-mediated metabolic remodeling in cardiac adaptation to hypoxia has yet be defined. Here, mice were housed for 3 wk before vivo contractile function was measured using cine MRI. In isolated, perfused hearts, energetics 31P magnetic resonance spectroscopy (MRS), and glycolysis fatty acid oxidation [3H] labeling. Compared with a normoxic, chow-fed control mouse heart, decreased PPARa expression, oxidation, mitochondrial uncoupling...
Objective: Adenosine receptor activation has been implicated in the mechanism of ischaemic preconditioning protection. Evidence suggests adenosine A1 involvement, and possibly A3 involvement rabbit. This study investigated roles these receptors human preconditioning. Human A1- A3-selective compounds were chosen based on Ki values for inhibition N6-(4-amino-3-[125I]iodobenzyl)adenosine (125I-ABA) binding to stably expressed recombinant receptors. Cyclopentyladenosine (CPA), a 194-fold...
Basic and clinical studies have shown that bone marrow cell therapy can improve cardiac function following infarction. In experimental animals, reported stem cell-mediated changes range from no measurable improvement to the complete restoration of function. clinic, however, average in left ventricular ejection fraction is around 2% 3%. A possible explanation for discrepancy between basic results few used magnetic resonance (MR) imaging (MRI) methods were trials measuring Consequently, we...
Grafting of elastomeric biomaterial scaffolds may offer a radical strategy for the prevention heart failure after myocardial infarction by increasing efficacy stem cell delivery as well acting mechanical restraint devices to constrain scar expansion. Biomaterials can be partially optimized in vitro, but their vivo performance is most critical and should ideally monitored serially noninvasively. We used magnetic resonance imaging (MRI) assess three scaffold materials with range structural...
Infarction irreversibly damages the heart, with formation of an akinetic scar that may lead to heart failure. Endogenous cardiac stem cells (CSCs) are a promising candidate cell source for restoring lost tissue and thereby preventing CSCs be isolated in vitro, via cardiospheres, give cardiosphere-derived (CDCs). Although qRT-PCR analyses CDCs have been performed, no justification selection housekeeping gene has published. Here, we evaluated most suitable RNA expression analysis cultured...
Background— Myocardial infarction (MI) is one of the leading causes heart failure. An increasing body evidence links alterations in cardiac metabolism and mitochondrial function with progression disease. The aim this work was to, therefore, follow vivo metabolic caused by MI, thereby allowing a greater understanding interplay between functional abnormalities. Methods Results— Using hyperpolarized carbon-13 ( 13 C)-magnetic resonance spectroscopy, were assessed for 22 weeks after surgically...
The aim of this study was to determine if hyperpolarized [1,4-
The type 2 diabetic heart oxidizes more fat and less glucose, which can impair metabolic flexibility function. Increased sarcolemmal fatty acid translocase (FAT/CD36) imports into the myocardium, feeding increased oxidation elevated lipid deposition. Unlike other modulators that target mitochondrial oxidation, we proposed pharmacologically inhibiting uptake, as primary step in pathway, would provide an alternative mechanism to rebalance metabolism prevent accumulation following hypoxic...
Abstract Duchenne muscular dystrophy (DMD) is a fatal neuromuscular disorder caused by mutations in the Dmd gene. In addition to skeletal muscle wasting, DMD patients develop cardiomyopathy, which significantly contributes mortality. Antisense oligonucleotides (AOs) are promising therapy, restoring functional dystrophin protein exon skipping. However, major limitation with current AOs absence of correction heart. Pip peptide-AOs demonstrate high activity cardiac muscle. To determine their...
Medium-chain length polyhydroxyalkanoates (MCL-PHAs) have demonstrated exceptional properties for cardiac tissue engineering (CTE) applications. Despite prior work on MCL-PHA/polycaprolactone (PCL) blends, optimal scaffold production and use as an alternative delivery route controlled release of seeded progenitor cells (CPCs) in CTE applications vivo has been lacking. We present herein applicability MCL-PHA/PCL (95/5 wt %) blends fabricated thin films with improved performance compared to...