About
42
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Introduction
I am a Senior Lecturer within the Swansea University Medical School. I have a long standing interest in the role of extracellular vesicles (EVs) as modulators of the tumour microenvironment and as a source of disease biomarkers.
Areas of research include the isolation of EVs from biofluid, potential use of EVs as a source of biomarkers, functional analysis of EVs, and the role of EVs in rare diseases (e.g. Tuberous Sclerosis Complex).
Additional affiliations
November 2014 - present
October 2008 - October 2014
Publications
Publications (42)
Urinary extracellular vesicles (uEVs) are enriched with glycosylated proteins which have been extensively studied as putative biomarkers of urological cancers. Here, we characterized the glycosylation and integrin profile of EVs derived from urological cancer cell lines. We used fluorescent europium-doped nanoparticles coated with lectins and antib...
Urine is commonly used for clinical diagnosis and biomedical research. The discovery of extracellular vesicles (EV) in urine opened a new fast-growing scientific field. In the last decade urinary extracellular vesicles (uEVs)were shown tomirrormolecular processes as well as physiological and pathological conditions in kidney, urothelial and prostat...
Adenoviral (Ad) vectors represent promising vaccine platforms for infectious disease. To overcome pre-existing immunity to commonly used human adenovirus serotype 5 (Ad5), vectors based on rare species or non-human Ads are being developed. However, these vectors often exhibit reduced potency compared with Ad5, necessitating the use of innovative ap...
The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many...
The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many...
This report summarises the presentations and activities of the ISEV Workshop on extracellular vesicle biomarkers held in Birmingham, UK during December 2017. Among the key messages was broad agreement about the importance of biospecimen science. Much greater attention needs to be paid towards the provenance of collected samples. The workshop also h...
Communication between diseased cells and the microenvironment is a complex yet crucial element in progression of varied pathological processes. Recent studies in cancer highlight an important role for small extracellular nanovesicles secreted by cancer cells as modulators of cancer-associated stroma, leading to enhanced angiogenesis and metastatic...
The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many...
Exosomes are a distinct population of extracellular vesicles of endocytic origin with a protein repertoire similar to the parent cell. Although tumour-derived exosomes harbour immunosuppressive characteristics, they also carry tumour antigens and thus potentially contribute to immune activation. The aim of this study was to examine the impact of pr...
Extracellular vesicles, including exosomes, are naturally derived nanovesicles generated in and released by numerous cell types. As extracellular entities they have the capacity to interact with neighbouring cells and distant tissues and affect physiological processes as well as being implicated in numerous diseases including tumorigenesis and neur...
Proteomics analysis of biofluid-derived vesicles holds enormous potential for discovering non-invasive disease markers. Obtaining vesicles of sufficient quality and quantity for profiling studies has, however, been a major problem, as samples are often replete with co-isolated material that can interfere with the identification of genuine low abund...
Proteomics analysis of vesicles isolated from plasma and urine of prostate cancer patients using a multiplex, aptamer-based protein array
Proteomics analysis of vesicles isolated from plasma and urine of prostate cancer patients using a multiplex, aptamer-based protein array
Proteomics analysis of vesicles isolated from plasma and urine of prostate cancer patients using a multiplex, aptamer-based protein array
Proteomics analysis of vesicles isolated from plasma and urine of prostate cancer patients using a multiplex, aptamer-based protein array
Proteomics analysis of vesicles isolated from plasma and urine of prostate cancer patients using a multiplex, aptamer-based protein array
Introduction: Exosomes originate in multivesicular endosomes (MVEs)
and are expelled into the extracellular space to mediate important
effects. In cancer, local interaction of exosomes with stromal cells
(fibroblasts) and angiogenic precursors serves to promote tumour
growth and progression. Secreted exosomes are known to be
heterogeneous, in terms...
Changes within interstitial stromal compartments often accompany carcinogenesis, and this is true of prostate cancer. Typically, the tissue becomes populated by myofibroblasts that can promote progression. Not all myofibroblasts exhibit the same negative influence, however, and identifying the aggressive form of myofibroblast may provide useful inf...
Proteomic studies of circulating vesicles are hampered by difficulties in purifying vesicles from plasma and serum. Isolations are contaminated with high-abundance blood proteins that may mask genuine vesicular-associated proteins and/or simply provide misleading data. In this brief report, we explored the potential utility of a commercially availa...
The tumour microenvironment is a highly complex and dynamic tissue. It comprises not only neoplastic cells, but also other resident cells within the milieu such as stroma and vascular cells in addition to a variable cellular infiltrate from the periphery. A host of soluble factors such as growth factors, chemokines, eicosanoids soluble metabolites...
Tumor-associated stromal myofibroblasts are essential for the progression and metastatic spread of solid tumors. Corresponding myeloid cell infiltration into primary tumors is a negative prognostic factor in some malignancies. The aim of this study was to define the exact role of stromal myofibroblasts and stromal factors in early prostate carcinom...
Stromal fibroblasts become altered in response to solid cancers, to exhibit myofibroblastic characteristics, with disease promoting influence. Infiltrating mesenchymal stem cells (MSC) may contribute towards these changes, but the factors secreted by cancer cells that impact MSC differentiation are poorly understood.
We investigated the role of nan...
We have used a novel affinity-based proteomics technology to examine the protein signature of small secreted extracellular vesicles called exosomes. The technology uses a new class of protein binding reagents called SOMAmers® (Slow Off-rate Modified Aptamers), and allows the simultaneous precise measurement of over 1000 proteins. Exosomes were high...
Activation of myofibroblast rich stroma is a rate-limiting step essential for cancer progression. The responsible factors are not fully understood, but TGFβ1 is probably critical. A proportion of TGFβ1 is associated with extracellular nano-vesicles termed exosomes, secreted by carcinoma cells, and the relative importance of soluble and vesicular TG...
We propose a straightforward method to estimate the purity of vesicle preparations by comparing the ratio of nano-vesicle counts to protein concentration, using tools such as the increasingly available NanoSight platform and a colorimetric protein assay such as the BCA-assay. Such an approach is simple enough to apply to every vesicle preparation w...
We propose a straightforward method to estimate the purity of vesicle preparations by comparing the ratio of nano-vesicle counts to protein concentration, using tools such as the increasingly available NanoSight platform and a colorimetric protein assay such as the BCA-assay. Such an approach is simple enough to apply to every vesicle preparation w...
Extracellular adenosine is elevated in cancer tissue, and it negatively regulates local immune responses. Adenosine production from extracellular ATP has attracted attention as a mechanism of regulatory T cell-mediated immune regulation. In this study, we examined whether small vesicles secreted by cancer cells, called exosomes, contribute to extra...
Aberrant expression of the human hyaluronan synthase 2 (HAS2) gene has been implicated in the pathology of malignancy, pulmonary arterial hypertension, osteoarthritis, asthma, thyroid dysfunction, and large organ fibrosis. Renal fibrosis is associated with increased cortical synthesis of hyaluronan (HA), an extracellular matrix glycosaminoglycan, a...
There is a growing interest in the cell-cell communication roles in cancer mediated by secreted vesicles termed exosomes. In this study, we examined whether exosomes produced by cancer cells could transmit information to normal stromal fibroblasts and trigger a cellular response. We found that some cancer-derived exosomes could trigger elevated α-s...
Myofibroblasts are contractile cells that are characterized by the expression of alpha-smooth muscle actin and mediate the closure of wounds and the formation of collagen-rich scars. Their presence in organs such as lungs, liver, and kidney has long been established as a marker of progressive fibrosis. The transforming growth factor beta(1)-driven...
The thyrotropin receptor (TSHR) is expressed during lineage-specific differentiation (e.g. adipogenesis) and is activated by TSH, thyroid-stimulating antibodies, and gain-of-function mutations (TSHR*). Comparison
of gene expression profiles of nonmodified human preadipocytes (n = 4) with the parallel TSHR* population revealed significant up-regulat...
The differentiation of resident fibroblasts to myofibroblasts is central to wound healing. In the context of organ fibrosis, however, persistence of these myofibroblasts is associated with progressive disease. This study examines mechanisms controlling the maintenance of the myofibroblast phenotype. Myofibroblasts were induced by adding transformin...
Projects
Projects (2)
Investigate the role of exosomal heparan sulphate proteoglycans (HSPGs) in prostate cancer development. Identify specific HSPGs present on prostate cancer exosomes, investigate the function of these HSPGs in stromal cell differentiation and explore their potential as biomarkers for aggressive prostate cancer.
Stromal tissue surrounding glandular structures of the prostate is
composed of smooth muscle, fibroblasts, and endothelial cells. During
carcinogenesis the stroma becomes aberrantly altered and populated by
myofibroblasts. Such changes are associated with treatment-resistant
prostate cancer and are indicative of aggressive disease. The
mechanism which drives this process, however, remains unclear.
Fibroblasts undergo myofibroblastic differentiation in response to TGFβ.
Many studies focus on the role of soluble-TGFβ; this may, however, be a
poor representation of the tumour environment. Prostate cancer cells
secrete TGFβ in association with nano-metre sized vesicles, termed
exosomes. These exosomes aberrantly activate stromal cells to a
phenotype mimicking that of diseased stroma. Soluble-TGFβ, however,
could not. We found that exosomal expression of heparan sulphate
proteoglycans (HSPGs) was essential for functional delivery of TGFβ.
Several HSPGs are known to regulate TGFβ signalling and are over
expressed in prostate cancer tissue. Our supporting data demonstrates
an elevation in HSPG expression on serum-derived exosomes from patients with prostate cancer. We hypothesise that exosomal-HSPGs are
necessary for stromal activation, and may therefore be utilised in a
simple assay to distinguish indolent from aggressive disease. This will be
the first study to investigate the role of exosomal-HSPGs during prostate
cancer development.
