A5071148454- Congenital heart defects research
- Axon Guidance and Neuronal Signaling
- Angiogenesis and VEGF in Cancer
- Tissue Engineering and Regenerative Medicine
- Lymphatic System and Diseases
- Congenital Heart Disease Studies
- Cardiac Fibrosis and Remodeling
- Zebrafish Biomedical Research Applications
- Cardiovascular Health and Disease Prevention
- Developmental Biology and Gene Regulation
- Neurogenesis and neuroplasticity mechanisms
- Coronary Artery Anomalies
- Pluripotent Stem Cells Research
- 3D Printing in Biomedical Research
- Microfluidic and Bio-sensing Technologies
- Neonatal Respiratory Health Research
- Neuroscience and Neural Engineering
- Electrospun Nanofibers in Biomedical Applications
- Renal and related cancers
- Apelin-related biomedical research
- Chromatin Remodeling and Cancer
- GDF15 and Related Biomarkers
- Cardiac Valve Diseases and Treatments
- Thyroid Cancer Diagnosis and Treatment
- Cardiomyopathy and Myosin Studies
University of Oxford
2013-2025
King's College London
2012-2025
British Heart Foundation
2020-2022
University College London
2007-2016
St Thomas' Hospital
2012
William Harvey Research Institute
2012
University of Manchester
2012
St. Luke's Episcopal Hospital
2012
Cornell University
2012
Cardiovascular Institute of the South
2012
Abstract Canonical roles for macrophages in mediating the fibrotic response after a heart attack include extracellular matrix turnover and activation of cardiac fibroblasts to initiate collagen deposition. Here we reveal that directly contribute forming post-injury scar. Unbiased transcriptomics shows an upregulation collagens both zebrafish mouse following injury. Adoptive transfer macrophages, from either collagen-tagged or adult GFP tpz -collagen donors, enhances scar formation via cell...
Myocardial infarction (MI) arising from obstruction of the coronary circulation engenders massive cardiomyocyte loss and replacement by non-contractile scar tissue, leading to pathological remodeling, dysfunction, ultimately heart failure. This is presently a global health problem for which there no effective cure. Following MI, innate immune system directs phagocytosis dead cell debris in an effort stimulate repopulation tissue renewal. In mammalian adult heart, however, persistent influx...
During development, the axons of retinal ganglion cell (RGC) neurons must decide whether to cross or avoid midline at optic chiasm project targets on both sides brain. By combining genetic analyses with in vitro assays, we show that neuropilin 1 (NRP1) promotes contralateral RGC projection mammals. Unexpectedly, NRP1 ligand involved is not an axon guidance cue class 3 semaphorin family, but VEGF164, neuropilin-binding isoform classical vascular growth factor VEGF-A. VEGF164 expressed and...
Macrophages are components of the innate immune system with key roles in tissue inflammation and repair. It is now evident that macrophages also support organogenesis, but few studies have characterized their identity, ontogeny function during heart development. Here, we show distribution prevalence resident subepicardial compartment developing coincides emergence new lymphatics, interact closely nascent lymphatic capillaries. Consequently, global macrophage deficiency led to extensive...
Blood vessels and neurons share several types of guidance cues cell surface receptors to control their behaviour during embryogenesis. The transmembrane protein NRP1 is present on blood nerves. binds two structurally diverse ligands, the semaphorin SEMA3A VEGF164 isoform vascular endothelial growth factor. was originally identified as a repulsive cue for developing axons that acts by signalling through receptor complexes containing plexins. In vitro, also inhibits integrin function competes...
Neural crest cells (NCCs) are highly motile embryonic stem that delaminate from the neuroectoderm early during vertebrate embryogenesis and differentiate at defined target sites into various essential cell types. To reach their targets, NCCs follow 1 of 3 sequential pathways correlate with NCC fate. The firstborn travel ventrally alongside intersomitic blood vessels to form sympathetic neuronal progenitors near dorsal aorta, while lastborn migrate superficially beneath epidermis give rise...
Neuropilin (NRP) receptors and their class 3 semaphorin (SEMA3) ligands play well-established roles in axon guidance, with loss of NRP1, NRP2, SEMA3A or SEMA3F causing defasciculation errors growth cone guidance peripherally projecting nerves. Here we report that NRP1 NRP2 also impairs sensory neuron positioning the mouse head, this defect is a consequence inappropriate cranial neural crest cell migration. Specifically, cells move into normally crest-free territory between trigeminal hyoid...
Cardiovascular disease remains the major cause of mortality, and cardiac cell therapy has recently emerged as a paradigm for heart repair. The epicardium is layer mesothelial cells covering that during development contributes to different cardiovascular lineages, including cardiomyocytes, but which becomes quiescent after birth. We previously revealed peptide thymosin beta 4 (Tβ4) can reactivate adult epicardium-derived (EPDCs) myocardial infarction (MI), proliferate, differentiate into...
Epicardium-derived cells (EPDCs) contribute cardiovascular cell types during development and in adulthood respond to Thymosin β4 (Tβ4) myocardial infarction (MI) by reactivating a fetal gene programme promote neovascularization cardiomyogenesis. The mechanism for epicardial (re-)activation remains elusive. Here we reveal that BRG1, the essential ATPase subunit of SWI/SNF chromatin-remodelling complex, is required expression Wilms' tumour 1 (Wt1), EPDC activation subsequent differentiation...
The epicardium is essential for mammalian heart development. At present our understanding of the timing and morphogenetic events leading to human development has essentially been extrapolated from model organisms. Here, we studied primary tissue samples characterise We reveal that begins envelop myocardial surface at Carnegie Stage (CS) 11 this process completed by CS15, earlier than previously inferred avian studies. Contrary prevailing dogma, formed not a simple squamous epithelium...
The aim of this study was to clarify the role vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) pathways in thyroid tumourigenesis.We examined VEGF, VEGFR-1 VEGFR-2 expression on 34 papillary carcinomas (PTCs), 18 follicular (FTCs), eight poorly differentiated (PDTCs) a tumour-derived cell line (NPA'87) by immunohistochemistry, reverse transcriptase PCR, immunofluorescence Western blotting.We have demonstrated that significantly (P < 0.05) more prevalent PTCs (79%) than...
Significance Neural progenitor cells (NPCs) proliferate to generate precursors for new neurons. To sustain this process, NPCs balance self-renewal with the generation of progeny committed neuronal differentiation. In adult mammalian brain, blood vessels and vessel-derived factors help regulate by modulating NPC proliferation quiescence, independently vascular roles in providing oxygen nutrients. contrast, it has been proposed that vasculature regulates behavior developing forebrain...
Significance How cardiac and skeletal muscle function is maintained regulated important in terms of understanding normal physiology muscle-based disease (myopathy). The two striated types are structurally functionally divergent, suggesting alternate molecular regulation. However, our discovery that the transcription factor Prox1 controls same fast gene program both slow significant assigning a common genetic mechanism to development. These studies establish novel model human dilated...
Axon guidance cues direct nerves in the heart during development, disease and regeneration. These determine cardiac innervation patterning by regulating balance between chemo-attraction chemo-repulsion. However, role of one most crucial ligand-receptor combinations among axon molecules, Slit chemo-active ligands their Roundabout (Robo) transmembrane receptors, remains unknown patterning. To test if Slit-Robo signalling is important for guidance, we analysed Robo mouse knock-outs....
Abstract In adult mice, surgically-induced myocardial infarction (MI) activates the cardiac lymphatics, which undergo sprouting angiogenesis, draining interstitial fluid and trafficking macrophages to mediastinal lymph nodes (MLNs), improving function. Given importance of lymphatics post-MI, we investigated their role across neonatal “regenerative window”. At post-natal day 1 (P1) mice fully regenerate heart following MI, in a macrophage-dependent manner, whereas equivalent injury at P7...
<title>Abstract</title> In humans, new-born infants have the ability to regenerate their heart during early life. This is modelled in mouse, where regenerative capacity maintained for first week after birth but lost thereafter. Reactivation of this process holds significant therapeutic potential, however, molecular pathways that might be targeted extend neonatal regeneration remain elusive. Here, we explore a role hypoxia and HIF signalling on regulation epicardial activity which essential...
The chemokine receptor CCR7 plays a critical role in lymphocyte and dendritic cell trafficking into within lymph nodes, the preferential metastatic site for papillary (PTC) medullary (MTC) thyroid carcinomas. In order to determine possible mediating behaviour of carcinomas, we analysed its expression normal tumoral tissues different histotypes studied vitro effects activation by ligand, CCL21. Using real-time quantitative-PCR, observed that was higher PTCs MTCs than follicular poorly...
During heart development, epicardial cells residing within the outer layer undergo epithelial-mesenchymal transition (EMT) and migrate into underlying myocardium to support organ growth morphogenesis. Disruption of EMT results in embryonic lethality, yet its regulation is poorly understood. Here, we report mesothelial mouse at ultra-high resolution using scanning electron microscopy combined with immunofluorescence analyses. We identified morphologically active regions that associated key...