A5050721723- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Neonatal Respiratory Health Research
- Pulmonary Hypertension Research and Treatments
- Medical Imaging and Pathology Studies
- Inhalation and Respiratory Drug Delivery
- TGF-β signaling in diseases
- RNA Interference and Gene Delivery
- Lung Cancer Treatments and Mutations
- Occupational and environmental lung diseases
- Systemic Sclerosis and Related Diseases
- Blood Coagulation and Thrombosis Mechanisms
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Cytokine Signaling Pathways and Interactions
- Peptidase Inhibition and Analysis
- Inflammatory mediators and NSAID effects
- Virus-based gene therapy research
- Pleural and Pulmonary Diseases
- Collagen: Extraction and Characterization
- Sarcoidosis and Beryllium Toxicity Research
- Occupational exposure and asthma
- Asthma and respiratory diseases
- Protease and Inhibitor Mechanisms
- Viral gastroenteritis research and epidemiology
- Cystic Fibrosis Research Advances
- Connective tissue disorders research
University College London
2016-2025
Centre for Inflammation Research
2013-2022
The Royal Free Hospital
1998-2012
Wilhelminen Hospital
2006
Sir Charles Gairdner Hospital
2003
The University of Western Australia
2003
UCL Australia
2000
University of London
1986-1996
Instituto Nacional de Cancerología
1996
Royal Brompton Hospital
1981-1994
Acute respiratory distress syndrome (ARDS) is an often fatal condition for which a genetic predisposition postulated, although no specific genes have been identified to date. Angiotensin converting enzyme (ACE) has potential role in the pathogenesis of ARDS via effects on pulmonary vascular tone/permeability, epithelial cell survival, and fibroblast activation. Forty-seven percent variance plasma ACE activity accounted by insertion/deletion (I/D) polymorphism, D allele being associated with...
BackgroundIdiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with high mortality, uncertain cause, and few treatment options. Studies have identified significant genetic risk associated the development of IPF; however, mechanisms by which factors promote IPF remain unclear. We aimed to identify variants susceptibility provide mechanistic insight using gene protein expression analyses.MethodsWe used two-stage approach: genome-wide association study in patients European...
Rationale: Idiopathic pulmonary fibrosis (IPF) is a complex lung disease characterized by scarring of the that believed to result from an atypical response injury epithelium. Genome-wide association studies have reported signals implicating multiple pathways including host defense, telomere maintenance, signaling, and cell-cell adhesion.Objectives: To improve our understanding factors increase IPF susceptibility identifying previously unreported genetic associations.Methods: We conducted...
Idiopathic pulmonary fibrosis (IPF) is the most rapidly progressive and fatal of all fibrotic conditions with no curative therapies. Common pathomechanisms between IPF cancer are increasingly recognised, including dysfunctional pan-PI3 kinase (PI3K) signalling as a driver aberrant proliferative responses. GSK2126458 novel, potent, PI3K/mammalian target rapamycin (mTOR) inhibitor which has recently completed phase I trials in oncology setting. Our aim was to establish scientific dosing...
Objective— Cyclooxygenase (COX)-2 is a key regulatory enzyme in the synthesis of prostanoids associated with trauma and inflammation. We investigated COX-2 gene for functional variants that may influence susceptibility to disease. Methods Results— The promoter was screened healthy subjects by use polymerase chain reaction-based methods. Promoter activity using reporter expression experiments human lung fibroblasts. Patients undergoing coronary artery bypass graft surgery, measurements plasma...
Mast cells play a potentially important role in fibroproliferative diseases, releasing mediators including tryptase that are capable of stimulating fibroblast proliferation and procollagen synthesis. The mechanism by which stimulates is unclear, although recent studies suggest it can activate protease-activated receptor (PAR)-2. We therefore investigated the PAR-2 tryptase-induced human fetal lung adult parenchymal airway fibroblasts and, for comparative purposes, dermal fibroblasts....
The fibroproliferative phase of acute respiratory distress syndrome (ARDS) has traditionally been regarded as a late event but recent studies that suggest increased lung collagen turnover within 24 h diagnosis challenge this view. We hypothesized fibroproliferation is initiated early in ARDS, characterized by the presence fibroblast growth factor activity and would relate to clinical outcome. Patients fulfilling American/European Consensus Committee criteria for ARDS control patients...
Angiotensin II (ANG II), generated by activation of local renin-angiotensin systems, is believed to play an important role in tissue repair and remodeling, part via transforming growth factor-β (TGF-β). Angiotensin-converting enzyme (ACE) inhibitors have been shown abrogate experimental lung injury a number potential mechanisms; however, the potentially fibroproliferative for ANG has not characterized. We hypothesized that, after injury, would stimulate fibroblast procollagen synthesis...
The expression of renin-angiotensin system components and the elevation angiotensin-converting enzyme (ACE) in a number fibrotic lung diseases suggests angiotensin II (AII) could play role pathogenesis pulmonary fibrosis. However, effect AII on fibroblasts has not previously been assessed mechanisms by which induces cell proliferation mesenchymal cells are fully understood. We have examined ability to stimulate fetal adult human fibroblast vitro. In particular, we receptor subtypes involved...
During developmental growth, collagens are believed to be continuously deposited into an extracellular matrix which is increasingly stabilized by the formation of covalent cross-links throughout life. However, age-related changes in rates synthetic and degradative processes less well understood. In present study we measured collagen synthesis vivo using a flooding dose unlabelled proline given with [14C]proline determining production hydroxy[14C]proline. Degradation newly synthesized was...
Rationale: Patients with idiopathic pulmonary fibrosis (IPF), a progressive disease dismal prognosis, exhibit an unexplained disparity of increased alveolar epithelial cell (AEC) apoptosis but reduced fibroblast apoptosis.Objectives: To examine whether the failure patients IPF to up-regulate cyclooxygenase (COX)-2, and thus antifibrotic mediator prostaglandin (PG)E2, accounts for this imbalance.Methods: Fibroblasts primary type II AECs were isolated from control fibrotic human lung tissue....
Abstract Idiopathic pulmonary fibrosis (IPF) is a fatal disease that unresponsive to current therapies and characterized by excessive collagen deposition subsequent fibrosis. While inflammatory cytokines, including interleukin (IL)‐6, are elevated in IPF, the molecular mechanisms underlie this incompletely understood, although development of believed depend on canonical transforming growth factor (TGF)‐β signalling. We examined bleomycin‐induced inflammation mice carrying mutation shared...
Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease associated with chronic inflammation and tissue remodelling leading to fibrosis, reduced function, respiratory failure death. Bleomycin (Blm)-induced in mice replicates several clinical features of human IPF, including prominent lymphoid aggregates predominantly B-cells that accumulate the adjacent areas active fibrosis. We have shown previously a requirement for development Blm-induced mice. To determine therapeutic...
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Thrombin is a multifunctional serine protease that has crucial role in blood coagulation. It also potent mesenchymal cell mitogen and chemoattractant might therefore have an important the recruitment local proliferation of cells at sites tissue injury. We hypothesized thrombin affect deposition connective proteins these by directly stimulating fibroblast procollagen production. To address this hypothesis, effect on production gene expression human foetal lung fibroblasts was assessed over 48...