A5016553178- Cardiac electrophysiology and arrhythmias
- Receptor Mechanisms and Signaling
- Takotsubo Cardiomyopathy and Associated Phenomena
- Ion channel regulation and function
- Nitric Oxide and Endothelin Effects
- Phosphodiesterase function and regulation
- Cardiomyopathy and Myosin Studies
- Cardiac Imaging and Diagnostics
- Analytical Chemistry and Sensors
- Heart Failure Treatment and Management
- Mitochondrial Function and Pathology
- Dermatologic Treatments and Research
- Neurosurgical Procedures and Complications
- Electroconvulsive Therapy Studies
- Cardiac Ischemia and Reperfusion
- Neuroscience and Neural Engineering
- Electrochemical Analysis and Applications
- Hair Growth and Disorders
- Cardiovascular Issues in Pregnancy
- Cardiac Fibrosis and Remodeling
- Simulation-Based Education in Healthcare
- Migraine and Headache Studies
- Cardiac Structural Anomalies and Repair
- Pharmacological Effects and Toxicity Studies
- Cardiac Arrhythmias and Treatments
Imperial College London
2012-2023
Lung Institute
2012-2023
University of Roehampton
2021-2023
NHS Blood and Transplant
2023
Hammersmith Hospital
2017-2022
Eli Lilly (United States)
2020-2022
University of British Columbia Hospital
2012
Xuzhou Medical College
2012
NIHR Royal Brompton Cardiovascular Biomedical Research Unit
2012
Royal Brompton Hospital
2012
Background— Takotsubo cardiomyopathy is an acute heart failure syndrome characterized by myocardial hypocontractility from the mid left ventricle to apex. It precipitated extreme stress and can be triggered intravenous catecholamine administration, particularly epinephrine. Despite its grave presentation, rapidly reversible, with generally good prognosis. We hypothesized that this represents switching of epinephrine signaling through pleiotropic β 2 -adrenergic receptor (β AR) canonical...
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...
The purpose of this study was to investigate whether caveolin-3 (Cav3) regulates localization β2-adrenergic receptor (β2AR) and its cAMP signaling in healthy or failing cardiomyocytes. We co-expressed wildtype Cav3 dominant-negative mutant (Cav3DN) together with the Förster resonance energy transfer (FRET)-based sensor Epac2-camps adult rat ventricular myocytes (ARVMs). FRET scanning ion conductance microscopy were used locally stimulate β2AR measure cytosolic cAMP. overexpression increased...
Abstract Aims Takotsubo syndrome (TTS) is an acute heart failure, typically triggered by high adrenaline during physical or emotional stress. It distinguished from myocardial infarction (MI) a characteristic pattern of ventricular basal hypercontractility with hypokinesis apical segments, and in the absence culprit coronary occlusion. We aimed to understand whether recently discovered circulating biomarkers miR-16 miR-26a, which differentiate TTS MI at presentation, were mechanistically...
Arrhythmogenesis during heart failure is a major clinical problem. Regional electrical gradients produce arrhythmias, and cellular ionic transmembrane are its originators. We investigated whether the nanoscale mechanosensitive properties of cardiomyocytes from failing hearts have bearing upon initiation abnormal activity. Hydrojets through nanopipette indent specific locations on sarcolemma initiate intracellular calcium release in both healthy cardiomyocytes, as well human cardiomyocytes....
Cardiomyocyte β2-adrenergic receptor (β2AR) cyclic adenosine monophosphate (cAMP) signalling is regulated by the receptors' subcellular location within transverse tubules (T-tubules), via interaction with structural and regulatory proteins, which form a signalosome. In chronic heart failure (HF), β2ARs redistribute from T-tubules to cell surface, disrupts functional signalosomes leads diffuse cAMP signalling. However, consequences of changes upon β2AR-cAMP during progression hypertrophy...
The field of cardiomyocyte mechanobiology is gaining significant attention, due to accumulating evidence concerning the role cellular mechanical effects on integrated function heart. To date, protein titin has been demonstrated as a major contributor cardiomyocytes Young’s modulus (YM). microtubular network represents another potential regulator cardiac mechanics. However, contribution microtubules (MTs) membrane YM still understudied and not interrogated in context myocardial infarction...
Cardiomyocyte β
Cyclic adenosine monophosphate (cAMP) regulates cardiac excitation-contraction coupling by acting in microdomains associated with sarcolemmal ion channels. However, local real time cAMP dynamics such has not been visualized before. We sought to directly monitor a microdomain formed around sodium-potassium ATPase (NKA) healthy and failing cardiomyocytes better understand alterations of compartmentation heart failure.A novel Förster resonance energy transfer (FRET)-based biosensor termed...
Alopecia areata (AA) is an autoimmune disease characterized by hair loss. Patients with AA experience a range of social and emotional impacts, the lack effective treatments multiple affected locations can deepen burden illness. The objective current study was to assess health-related quality life (HRQL) among patients AA, evaluate relationship between patient-reported severity, HRQL treatment patterns.A web survey completed participants recruited through National Areata Foundation. included...
The measurement of the contractile behavior single cardiomyocytes has made a significant contribution to our understanding physiology and pathophysiology myocardium. However, isolation introduces various technical statistical issues. Traditional video fluorescence microscopy techniques based around conventional systems result in low-throughput experimental studies, which cells are studied over course pharmacological or physiological intervention. We describe new approach these experiments...
Introduction We investigated the effect of partial mechanical unloading (PMU) heart on physiology calcium and beta-adrenoceptor-cAMP (βAR-cAMP) microdomains. Previous studies have PMU using a model heterotopic-heart lung transplantation (HTHAL). These demonstrated that disrupts structure cardiomyocytes handling. sought to understand these processes by studying L-Type Calcium Channel (LTCC) activity sub-type-specific βAR-cAMP signalling within cardiomyocyte membrane Method utilized an 8-week...
β
Takotsubo syndrome is a well-characterized cause of acute yet reversible heart failure associated with periods intense emotional stress, often mimicking on presentation an coronary syndrome. Animal models have been developed, either through the application stressor, or administration exogenous catecholamine. We found that in model isoproterenol-induced anesthetized rats hyperthermia (40-41°C) would occur after isoproterenol. Maintenance this result apical hypocontractility typical syndrome,...