A5076830473- Telomeres, Telomerase, and Senescence
- Renal and related cancers
- Birth, Development, and Health
- Immune cells in cancer
- Chronic Kidney Disease and Diabetes
- Parasites and Host Interactions
- Eosinophilic Esophagitis
- Hormonal Regulation and Hypertension
- Cardiac Fibrosis and Remodeling
- Renal and Vascular Pathologies
- Signaling Pathways in Disease
- Health, Environment, Cognitive Aging
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Clusterin in disease pathology
- Biomarkers in Disease Mechanisms
- Aortic aneurysm repair treatments
- Parasitic Diseases Research and Treatment
- Reproductive System and Pregnancy
- Single-cell and spatial transcriptomics
- Renal Transplantation Outcomes and Treatments
- Immune responses and vaccinations
- Organ Transplantation Techniques and Outcomes
- Epigenetics and DNA Methylation
- Studies on Chitinases and Chitosanases
- Asthma and respiratory diseases
University of Edinburgh
2014-2024
Centre for Inflammation Research
2008-2023
Queen's Medical Centre
2008-2023
The Queen's Medical Research Institute
2012-2018
British Heart Foundation
2015
Health Foundation
2008
MRC Clinical Trials Unit at UCL
2008
Senescent renal epithelia promote fibrosis and functional loss after injury, whereas depletion improves regeneration in aged or irradiated kidneys.
The prime function of classically activated macrophages (activated by Th1-type signals, such as IFN-gamma) is microbial destruction. Alternatively Th2 cytokines, IL-4 and IL-13) play important roles in allergy responses to helminth infection. We utilize a murine model filarial infection, which adult nematodes are surgically implanted into the peritoneal cavity mice, an vivo source alternatively macrophages. At 3 wk postinfection, exudate cell population dominated macrophages, termed...
The omentum is a visceral adipose tissue rich in fat-associated lymphoid clusters (FALCs) that collects peritoneal contaminants and provides first layer of immunological defense within the abdomen. Here, we investigated mechanisms mediate capture during peritonitis. Single-cell RNA sequencing spatial analysis omental stromal cells revealed surface FALCs were covered by CXCL1+ mesothelial cells, which termed FALC cover cells. Blockade CXCL1 inhibited recruitment aggregation neutrophils at...
Macrophages are the most abundant immune cell within ovary. Their dynamic distribution throughout ovarian cycle and heterogenic array of functions suggest involvement in various processes, but their functional role has yet to be fully established. The aim was induce conditional macrophage ablation elucidate putative macrophages maintaining integrity vasculature. Using CD11b-diphtheria toxin receptor (DTR) mouse, which expression human DTR is under control macrophage-specific promoter...
Progressive fibrosis is a feature of aging and chronic tissue injury in multiple organs, including the kidney heart. Glioma-associated oncogene 1 expressing (Gli1
Tissue resident macrophages have vital homeostatic roles in many tissues but their are less well defined the heart. The present study aimed to identify density, polarisation status and distribution of healthy murine heart investigate ability respond immune challenge. Histological analysis hearts from CSF-1 receptor (csf1-GFP; MacGreen) CX3CR1 (Cx3cr1(GFP/+)) reporter mice revealed a sparse population GFP positive that were evenly distributed throughout left right ventricular free walls...
Background. Acute rejection increases the risk of late renal allograft loss with tubular atrophy, interstitial fibrosis, and microvascular rarefaction. Evidence supports a role for macrophages in promoting injury, but pathogenic mechanisms are unclear. Using model acute rejection, we sought evidence macrophage-mediated endothelial cell cytotoxicity leading to microvasculature. Methods. We used transgenic conditional ablation strategy deplete circulating monocytes infiltrating after kidney...
Progressive fibrosis and maladaptive organ repair result in significant morbidity millions of premature deaths annually. Senescent cells accumulate with aging after injury are implicated fibrosis, but the mechanisms by which senescence influences poorly understood. Using 2 murine models repair, we show that obstructive generated senescent epithelia, persisted resolution original injury, promoted ongoing impeded adaptive repair. Depletion ABT-263 reduced reversed ureteric obstruction renal...
Liver transplantation is the only curative option for patients with end-stage liver disease. Despite improvements in surgical techniques, nonanastomotic strictures (characterized by progressive loss of biliary tract architecture) continue to occur after transplantation, negatively affecting function and frequently leading graft retransplantation. To study biological effects organ preservation before we generated murine models that recapitulate procurement static cold storage. In these...
We have previously demonstrated that neutrophil recruitment to the heart following myocardial infarction (MI) is enhanced in mice lacking 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates active glucocorticoid within cells from intrinsically inert metabolites. The present study aimed identify mechanism of regulation. In a mouse model MI, mobilization blood and were higher 11β-HSD1-deficient ( Hsd11b1 − / ) relative wild-type (WT) mice, despite similar initial injury circulating...
Global deficiency of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), an enzyme that regenerates glucocorticoids within cells, promotes angiogenesis, and reduces acute infarct expansion after myocardial infarction (MI), suggesting 11β-HSD1 activity has adverse influence on wound healing in the heart MI. The present study investigated whether could prevent development failure MI examined cardiomyocytes vascular smooth muscle cells confers this protection. Male mice with global 11β-HSD1, or...
Larvae of several common species parasitic nematodes obligately migrate through, and often damage, host lungs. The larvae induce strong pulmonary Type 2 immune responses, including T-helper (Th)2 cells as well alternatively activated macrophages (AAMphi) associated chitinase Fizz/resistin family members (ChaFFs), which are thought to promote tissue repair processes. Given the prevalence systemic or lung-resident 1-inducing pathogens in geographical areas endemic, we wished investigate impact...
BackgroundBone marrow transplantation (BMT) is commonly used in experimental studies to investigate the contribution of BM-derived circulating cells different disease processes. During investigating cardiac response acute myocardial infarction (MI) induced by permanent coronary ligation mice that had previously undergone BMT, we found BMT itself affects remodelling response.Methods and resultsCompared matched naive mice, animals developed significantly less post-MI adverse remodelling,...
Macrophage-colony stimulating factor (M-CSF) and granulocyte macrophage-colony (GM-CSF) play key roles in the differentiation of macrophages dendritic cells (DCs). We examined effect treatment with M-CSF-containing macrophage medium or GM-CSF-containing DC upon phenotype murine bone marrow-derived DCs. Culture for 5 days reduced F4/80 expression increased CD11c effectively T cell proliferation a mixed lymphocyte reaction. significantly phagocytosis both apoptotic latex beads strongly induced...
Alternative macrophage activation is largely defined by IL-4Rα stimulation but the contribution of Toll-like receptor (TLR) signaling to this phenotype not currently known. We have investigated status under Th2 conditions in absence core TLR adaptor molecule, MyD88. No impairment was observed ability MyD88-deficient bone marrow derived macrophages produce or express alternative markers, including arginase, RELM-α Ym1, response IL-4 treatment vitro. Further, we no difference peritoneal...
Abstract The pericardium is widely recognised for its lubricating and bio-mechanical properties. It also contains fat-associated lymphoid clusters (FALCs) immune functions have been overlooked. Here we aimed to assess the inflammatory activity of in patients who suffered a recent myocardial infarction (MI) determine importance repair remodelling murine MI model induced by coronary artery ligation (CAL). By comparing 18 F-fluorodeoxyglucose (FDG) with stable disease had MI, demonstrate that...
Abstract Cellular senescence drives organ fibrosis and ageing, accumulating evidence supports the ability of senescence-depleting drugs to improve outcomes in experimental models disease. The lack non-invasive biomarkers represents a major obstacle design human trials candidate senolytics. On samples from 51 patients with chronic kidney disease (CKD), we performed liquid chromatography mass spectrometry (LC-MS) analysis urine alongside immunofluorescence staining paired biopsies for p21,...
Abstract Progressive fibrosis and maladaptive organ repair result in significant morbidity millions of premature deaths annually. Senescent cells accumulate with ageing after injury are implicated fibrosis, but the mechanisms by which senescence influences poorly understood. Using two murine models we show that obstructive generates senescent epithelia persist resolution original injury, promote ongoing impede adaptive repair. Depletion ABT263 reduces reversed ureteric obstruction renal...