A5061606928- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- PI3K/AKT/mTOR signaling in cancer
- Mast cells and histamine
- Pancreatic and Hepatic Oncology Research
- Cardiovascular Effects of Exercise
- Cardiovascular Function and Risk Factors
- Pancreatic function and diabetes
- Chronic Lymphocytic Leukemia Research
- Cancer-related Molecular Pathways
- Cancer Mechanisms and Therapy
- Parkinson's Disease Mechanisms and Treatments
- Connexins and lens biology
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Chronic Myeloid Leukemia Treatments
- Mitochondrial Function and Pathology
- Neurological disorders and treatments
- Neuroscience and Neural Engineering
- Neuroscience and Neuropharmacology Research
- Ubiquitin and proteasome pathways
- Bone and Dental Protein Studies
- Nerve injury and regeneration
- Cancer-related molecular mechanisms research
- Cancer, Hypoxia, and Metabolism
- Adenosine and Purinergic Signaling
University of Surrey
2017-2025
Queen Mary University of London
2010-2019
University of Bari Aldo Moro
2011
Casa Sollievo della Sofferenza
2010
Istituti di Ricovero e Cura a Carattere Scientifico
2010
Umeå University
2004-2007
Ninewells Hospital
2003
University of Dundee
2001
Phosphoinositide 3-kinases (PI3Ks) are critical regulators of pancreatic β cell mass and survival, whereas their involvement in insulin secretion is more controversial. Furthermore, the different PI3Ks, class II isoforms were detected cells, although role still not well understood. Here we show that down-regulation PI3K isoform PI3K-C2α specifically impairs granule exocytosis rat insulinoma cells without affecting content, number granules at plasma membrane, or expression levels key proteins...
Phosphoinositide 3-kinase (PI3K) signaling is well established as important in cancer. To date most studies have been focused on the PI3K/p110α isoform, which has found to be mutated several different cancers. The aim of our study was determine specific PI3K isoforms are involved pancreatic ductal adenocarcinoma (PDAC) and investigate effects these proliferation, survival, induction Akt activation cancer cells.The expression all downstream targets analyzed by immunohistochemistry human...
Abstract Cardiac dysautonomia plays an important role in understanding Parkinson's disease (PD), with recent studies highlighting the presence of α‐synuclein cardiac tissue. We hypothesise that sympathetic dysregulation observed PD may involve pathological changes caused by stellate ganglia (SG). This study aimed to investigate α‐synucleinopathy SG genetic murine animal model. Mice overexpressing Ala30Pro (A30P) mutant were used. here demonstrate a technique for meticulously dissecting SG....
Abstract Stellate ganglia (SG) provide sympathetic innervation to the heart and may predispose myocardial conducting system arrhythmias. However, little is known about age‐related changes in electrophysiology of murine SG. We investigated alterations electrophysiological properties SG with aging. The loose patch clamp technique was adapted tissue investigate voltage‐gated ionic currents its neuronal cells. compared ventricular cells from young (4 months) aged (13 C57BL/6J mice explore their...
Caffeine is a naturally occurring methylxanthine that acts as non-selective adenosine receptor antagonist. Epidemiological studies demonstrated habitual coffee drinking to be significantly associated with liver cancer survival. We aimed investigate the effects of caffeine and its analog CGS 15943 on hepatocellular carcinoma (HCC) pancreatic adenocarcinoma (PDAC). demonstrate block proliferation in HCC PDAC cell lines by inhibiting PI3K/Akt pathway. Importantly kinase profiling assay reveals...
Alterations of the cell cycle checkpoint frequently occur during hepatocarcinogenesis. Dysregulation phosphatidylinositol-3-kinases (PI3K) signaling pathway is believed to exert a potential oncogenic effect in hepatocellular carcinoma (HCC), ultimately promoting tumor proliferation. However, impact PI3K on regulation remains unclear. We used combined loss- and gain-of-function approach address involvement p110γ HCC proliferation, apoptosis cycle. also investigated correlation between Ki-67...
The very aggressive nature and low survival rate of pancreatic ductal adenocarcinoma (PDAC) dictates the necessity to find novel efficacious therapies. Recent evidence suggests that phosphoinositide 3-kinase (PI3K) 3-phosphoinositide-dependent protein kinase 1 (PDK1) are key effectors oncogenic KRAS in PDAC. Herein, we report role mechanism action PDK1, a AGC family, PDAC cell lines were treated with selective PDK1 inhibitors or transfected specific PDK1-targeting siRNAs. In vitro vivo...
Abstract Catecholaminergic polymorphic ventricular tachycardia (CPVT) is associated with mutations in the cardiac ryanodine receptor (RyR2). These result stress‐induced arrhythmic episodes, clinical symptoms and prognosis reported more severe male than female patients. Murine homozygotic RyR2‐P2328S ( RyR2 S/S ) hearts replicate proarrhythmic CPVT phenotype of abnormal sarcoplasmic reticular Ca 2+ leak disrupted homeostasis. In addition, show decreased myocardial action potential conduction...
Summary Receptor tyrosine kinase (RTK) c‐Kit signalling is crucial for the proliferation, survival and differentiation of haematopoietic stem cells (HSCs). To further understand mechanisms underlying these events we explored how downstream mediators interact. The present study investigated function conventional protein Cs (c‐PKC) in mediated pathways HSC‐like cell lines. This analysis supported earlier findings, that steel factor (SF) activates c‐PKC, extracellular signal‐regulated (Erk) B...
A range of chronic clinical conditions accompany cardiomyocyte energetic dysfunction and constitute independent risk factors for cardiac arrhythmia. We investigated pro-arrhythmic arrhythmic phenotypes in energetically deficient C57BL mice with genetic ablation the mitochondrial promoter peroxisome proliferator-activated receptor-γ coactivator-1β (Pgc-1β), a known model ventricular Pro-arrhythmic cellular action potential (AP) characteristics were compared intact Langendorff-perfused hearts...
Increases in the prevalence of obesity, insulin resistance, and metabolic syndrome has led to increase atrial fibrillation (AF) cases developed world. These AF risk factors are associated with mitochondrial dysfunction, previously modelled using peroxisome proliferator activated receptor-γ (PPARγ) coactivator-1 (Pgc-1)-deficient murine cardiac models. We explored gene protein expression profiles selected molecular targets related electrophysiological function Pgc-1α−/− atria. qPCR analysis...
Ageing and chronic metabolic disorders are associated with mitochondrial dysfunction cardiac pro-arrhythmic phenotypes which were recently attributed to slowed atrial ventricular action potential (AP) conduction in peroxisome proliferator-activated receptor γ co-activator deficient (Pgc-1β-/-) mice.We compared expression levels of voltage-gated Na+ channel (NaV1.5) gap junction channels, Connexins 40 43 (Cx40 Cx43) the hearts young old, wild-type (WT) Pgc-1β-/- mice. This employed Western...