A5009546060- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Systemic Lupus Erythematosus Research
- Cell Adhesion Molecules Research
- HIV-related health complications and treatments
- HIV/AIDS drug development and treatment
- Platelet Disorders and Treatments
- HIV Research and Treatment
- Pleural and Pulmonary Diseases
- Cell death mechanisms and regulation
- Immune cells in cancer
- Erythrocyte Function and Pathophysiology
- Antiplatelet Therapy and Cardiovascular Diseases
- Monoclonal and Polyclonal Antibodies Research
- S100 Proteins and Annexins
- HIV/AIDS Research and Interventions
- Asthma and respiratory diseases
- Bone and Joint Diseases
- Infectious Aortic and Vascular Conditions
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Galectins and Cancer Biology
- Pharmacological Effects and Assays
- Kawasaki Disease and Coronary Complications
- COVID-19 Clinical Research Studies
- Tracheal and airway disorders
Imperial College London
2019-2025
University College London
2014-2023
Centre for Inflammation Research
2014-2020
Lung Institute
2020
Mayo Clinic in Florida
2019
Center for Rheumatology
2017
University of Cambridge
2015
Introduction The BIC-T&T study aimed to determine the efficacy of bictegravir/emtricitabine/tenofovir alafenamide (BIC/F/TAF) and darunavir/cobicistat/emtricitabine/tenofovir (DRV/c/F/TAF) at suppressing viral load in a two-arm, open-label, multi-centre, randomised trial under UK test-and-treat setting. This sub-study evaluate potential off-target cardiovascular impact by examining ex vivo platelet function.
Cyclic guanosine monophosphate (cGMP) is a second messenger produced by the NO-sensitive guanylyl cyclase (NO-GC). The NO-GC/cGMP pathway in platelets has been extensively studied. However, its role regulating biomechanical properties of not yet addressed and remains unknown. We therefore investigated stiffness living after treatment with NO-GC stimulator riociguat or activator cinaciguat using scanning ion conductance microscopy (SICM). Stimulation human murine cGMP-modulating drugs...
Background and purpose Some clinical studies have reported increased myocardial infarction in people living with human immunodeficiency virus (HIV) taking the antiretroviral abacavir sulphate (ABC). Given that contain confounding variables (e.g., HIV‐associated factors), we investigated pharmacological effects of antiretrovirals on platelet function HIV‐negative volunteers order to identify mechanisms cardiovascular risk. Experimental approach Platelets were isolated from healthy subjects...
People living with HIV on effective antiretroviral therapy are at increased risk of cardiovascular complications, possibly due to off-target drug effects. Some studies have associated myocardial infarction and endothelial dysfunction, but a link between function antiretrovirals has not been established.To determine the effects in common clinical use upon vitro better understand people HIV.Human umbilical cord vein cells or human coronary artery were pretreated abacavir sulphate (ABC),...
Neutrophilic inflammation correlates with mortality in fibrotic interstitial lung disease (ILD) however, the underlying mechanisms remain unclear. Neutrophil function is modulated by numerous factors, including integrin activation, inflammatory cytokines and hypoxia. Hypoxia has an important role may also contribute to pulmonary disease. We aimed determine how neutrophil activation occurs ILD relative importance of Using biopsies bronchoalveolar lavage (BAL) fluid from patients we...
Transforming growth factor-β1 (TGFβ1) is the key profibrotic cytokine in idiopathic pulmonary fibrosis (IPF), but primary source of this disease unknown. Platelets have abundant stores TGFβ1, although role these cells IPF ill-defined. In study, we investigated whether platelets, and specifically platelet-derived mediate progression. Patients with non-IPF patients were recruited to determine platelet reactivity, separate cohorts followed for mortality. To study TGFβ1 modulates (PF), mice a...
Abstract The importance of neutrophils in the pathogenesis autoimmune rheumatic diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), is increasingly recognised. Generation reactive oxygen species (ROS) release neutrophil extracellular traps (NETs) by activated are both thought to contribute pathology; although underlying mechanisms, particularly effects IgG autoantibodies upon function, not fully understood. Therefore, we determined whether purified from...
Head-to-head data for bictegravir/emtricitabine/tenofovir alafenamide (BIC/F/TAF; B) and darunavir/cobicistat/emtricitabine/tenofovir (DRV/c/F/TAF; D) are lacking in the context of rapid antiretroviral therapy (ART) initiation. This study, BIC-T&T, evaluates efficacy tolerability B vs D a UK test-and-treat setting.
Abstract Introduction People with HIV currently face a tenfold higher risk of developing cardiovascular disease (CVD) than those without HIV. Studies have shown various off‐target effects antiretroviral treatment (ART) on the system, but little is known about used integrase strand transfer inhibitors (INSTIs) platelets. Platelet activation associated increased CVD, thrombus formation, and release proinflammatory mediators, so exploring platelet from prescribed ART may contribute to...
Pulmonary tuberculosis is caused by inhalation of Mycobacterium tuberculosis, which damages the bronchial epithelial barrier to establish local infection. Matrix metalloproteinase -1 plays a crucial role in immunopathology causing breakdown type I collagen and cavitation, but this collagenase also potentially involved repair. We hypothesized that extracellular matrix modulates driven metalloproteinase-1 expression human cells, regulating respiratory cell migration Medium from monocytes...
Background The pre-symptomatic stage of Rheumatoid arthritis (RA) is associated with pro-inflammatory cytokines and autoantibodies. High levels epitope spread by factors (RhF) autoantibodies to citrullinated proteins signify progression towards disease expression. In established RA, the persistence high autoantibody reflects production both long-lived plasma cells short-lived plasmablasts. Neither relative contributions pathogenesis from either source, nor responsible for deciding fate...
<h3>Background</h3> Pulmonary Fibrosis (PF) is characterised by abnormal wound healing involving fibroblast proliferation, myofibroblast differentiation and increased extracellular matrix deposition. TGFβ an important driving force in fibrotic disease, however the source of this cytokine PF ill-defined. Platelets can release large amounts TGFβ, we, others, have shown platelet deposition lungs patients with idiopathic pulmonary fibrosis (IPF), although role these cells unknown....
<h3>Background</h3> Antiphosholipid antibodies (aPLs) are known to activate monocytes in the pathogenesis of antiphospholipid syndrome (APS), although precise mechanisms by which this activation occurs not fully understood. We have recently identified several novel protein targets using a comprehensive proteomic analysis human treated with IgG from patients APS. Amongst these lysosomal proteases, including cathepsin B and D were identified. These proteases important degradation, clearance...
Abstract Neutrophilic inflammation correlates with mortality in fibrotic interstitial lung disease (ILD) however, the underlying mechanisms remain unclear. We aimed to determine whether aberrant neutrophil activation is a feature of ILD and relative role hypoxia. used biopsies bronchoalveolar lavage (BAL) from patients investigate extent hypoxia lungs ILD. complemented these findings ex vivo functional studies neutrophils healthy volunteers effects demonstrate for first time HIF-1α staining...
Abstract Cyclic guanosine monophosphate (cGMP) is a second messenger produced by the NO-sensitive guanylyl cyclase (NO-GC) enzyme. In platelets, NO-GC/cGMP pathway inhibits aggregation. One aspect of inhibitory mechanism involves changes in cytoskeleton; however, molecular mechanisms underlying platelet inhibition and its correlation with cytoskeletal cellular stiffness are poorly understood. We measured individual platelets after treatment NO-GC stimulator riociguat or activator cinaciguat,...
targets for existing drugs, which could be repositioned use in these diseases.Methods: Chromatin interaction data T-and B-cells the 3 diseases was analyzed using CHiCAGO a score cut-off of ! 5. Interactions between disease regions and promoters were identified BEDTOOLS intersected with drug from DrugBank.Existing treatments each by presence relevant name indication field.Results: Overall 850 genes as interacting associated region.Of these, 61 are (303 drugs) (Table 1) 9 therapies used...
<h3>Purpose</h3> Antiphospholipid antibodies (aPL) activate monocytes in antiphospholipid syndrome (APS), although the precise mechanisms by which this activation occurs are not fully understood. We have identified several novel protein targets using proteomic analysis of human treated with APS-IgG. Amongst these lysosomal proteases cathepsin B and D were identified. The balance between different cathepsins is important degradation, apoptosis autophagy. Reduced increased L a phenotype...
Abstract Transforming growth factor-β1 (TGFβ1) is the key pro-fibrotic cytokine implicated in interstitial lung diseases (ILD), including idiopathic pulmonary fibrosis (IPF), but primary source of TGFβ1 these unknown. Platelets have abundant stores, however their role IPF ill-defined. We sought to investigate whether platelets or platelet-derived mediate disease progression. ILD/IPF and non-ILD patients were recruited determine platelet reactivity followed for mortality. To study modulates...