Dr Jason Webber
PCUK Research Fellow
- webberjp@cardiff.ac.uk
- +44 (0)29 2068 7306
- GF16, Tenovus Building, University Hospital of Wales, Heath Park, Cardiff, CF14 4XN
- Available for postgraduate supervision
Overview
'Exploring why some cancers are more aggressive than others'
I am a Prostate Cancer UK funded Research Fellow within the Division of Cancer & Genetics.
Research within my group focuses on the role of nanometre-sized vesicles, termed exosomes, as drivers of aggressive prostate cancer. We have previously demonstrated that cancer cell-derived exosomes can activate stromal cells, also present within the tumour microenvironment, thereby facilitating enhanced tumour growth. This function of exosomes is likely due to heparan sulphate proteoglycans (HSPGs), present on the exosome surface, which are required for exosome-mediated growth factor delivery. In addition to their functional role, such exosomal-HSPGs may serve as novel biomarkers capable of discriminating patients with aggressive forms of cancer from those with slow growing tumours.
Key words:
Exosomes, prostate cancer, stroma, heparan sulphate, proteoglycans
Biography
Career overview
- 2014 - present: Prostate Cancer UK Research Fellow, Division of Cancer & Genetics, Cardiff University
- July 2014: Visiting Post-Doctoral Researcher, CIC bioGUNE, Bilbao, Spain
- 2008 - 2014: Research Associate, Division of Cancer & Genetics, Cardiff University
Education & qualifications
- 2009: Ph.D. Cell Biology; Institute of Nephrology, School of Medicine, Cardiff University
- 2005: B.Sc. Biochemistry with Medical Biochemistry; School of Biosciences, Cardiff University
Honours and awards
- Prostate Cancer UK Career Development Fellowship (~£680k) - funded from Nov 2014 to Oct 2019
- Society for Endocrinology 2013 – Best Poster Presnetation.
- Cancer Research Wales Travel Grant (£500) – to attend ISEV 2013 Meeting, Boston, USA.
- Prostate Action Travel Grant (£700) – to attend ISEV 2012 Meeting, Gothenburg, Sweden.
- Velindre NHS Trust R & D Conference 2010 – Best Oral Presentation.
- Velindre NHS Trust R & D Conference 2009 – Best Newcomer.
- MR2-IRG Research Day, Cardiff University 2008 – Best Oral Presentation.
- Postgraduate Research Day, Cardiff University 2007 – Best Oral Presentation.
Professional memberships
- Founding member of the International Society for Extracellular Vesicles (2011 – present)
- Member of the European Academy for Tumour Immunology (2016 – present)
- Member of the UK Extracellular Vesicle Forum (2014 – present)
- Member of the Cardiff Institute of Tissue Engineering & Repair (2006 – present)
Speaking engagements
Invited seminars
- July 2016: Extracellular Vesices - Biology & Therapeutic Potential, Select Bio, Cambridge, UK
- June 2014: Research Seminar Series, CIC bioGUNE, Bilbao, Spain
- June 2012: Prostate Action - The Forum (10th Biennial Prostate Cancer Forum), Rotterdam, Netherlands
- Feb 2012: IRDB / Oncology Spring Seminar Series, Imperial College London, UK
- April 2011: Prostate Action - Blue Skies Research Meeting, Downing College, Cambridge, UK
Committees and reviewing
- 2010 - present: Member of the Cardiff University Genetic Modification and Biological Agents Safety Committee
- 2010 - present: Departmental Biological Safety Officer
Publications
2023
- Bhaoighill, M. N., Falcón-Pérez, J. M., Royo, F., Tee, A., Webber, J. and Dunlop, E. 2023. Tuberous Sclerosis Complex cell-derived EVs have an altered protein cargo capable of regulating their microenvironment and have potential as disease biomarkers. Journal of Extracellular Vesicles 12(6), article number: 12336. (10.1002/jev2.12336)
2021
- Lanning, B., Webber, J., Uysal-Ongane, P., Jiang, W. G., Clayton, A. and Dart, D. A. 2021. Prostate cancer cell extracellular vesicles increase mineralisation of bone osteoblast precursor cells in an in vitro model. Biology 10(4), article number: 318. (10.3390/biology10040318)
2020
- Rosas, M. et al. 2020. The procoagulant activity of tissue factor expressed on fibroblasts is increased by tissue factor-negative extracellular vesicles. PLoS ONE 15(10), article number: e0240189. (10.1371/journal.pone.0240189)
- Bliss, C. M. et al. 2020. Targeting antigen to the surface of EVs improves the in vivo immunogenicity of human and non-human adenoviral vaccines in mice. Molecular Therapy - Methods and Clinical Development 16, pp. 108-125. (10.1016/j.omtm.2019.12.003)
2018
- Théry, C. et al. 2018. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. Journal of Extracellular Vesicles 7(1), article number: 1535750. (10.1080/20013078.2018.1535750)
- Clayton, A. et al. 2018. Summary of the ISEV workshop on extracellular vesicles as disease biomarkers, held in Birmingham, UK, during December 2017. Journal of Extracellular Vesicles 7(1), article number: 1473707. (10.1080/20013078.2018.1473707)
- Yeung, V. et al. 2018. Rab35-dependent extracellular nanovesicles are required for induction of tumour supporting stroma. Nanoscale 10(18), pp. 8547-8559. (10.1039/C8NR02417K)
2017
- Roberts-Dalton, H. D. et al. 2017. Fluorescence labelling of extracellular vesicles using a novel thiol-based strategy for quantitative analysis of cellular delivery and intracellular traffic. Nanoscale 9(36), pp. 13693-13706. (10.1039/C7NR04128D)
- Salimu, J., Webber, J., Gurney, M., Al-Taei, S., Clayton, A. and Tabi, Z. 2017. Dominant immunosuppression of dendritic cell function by prostate-cancer-derived exosomes. Journal of Extracellular Vesicles 6(1), article number: 1368823. (10.1080/20013078.2017.1368823)
2016
- Welton, J. . L. et al. 2016. Proteomics analysis of vesicles isolated from plasma and urine of prostate cancer patients using a multiplex, aptamer-based protein array. Journal of Extracellular Vesicles 5, article number: 31209. (10.3402/jev.v5.31209)
- Webber, J. P., Spary, L. K., Mason, M. D., Tabi, Z., Brewis, I. A. and Clayton, A. 2016. Prostate stromal cell proteomics analysis discriminates normal from tumour reactive stromal phenotypes. Oncotarget 7, pp. 20124-20139. (10.18632/oncotarget.7716)
2015
- Webber, J. P., Yeung, V. and Clayton, A. 2015. Extracellular vesicles as modulators of the cancer microenvironment. Seminars in Cell and Developmental Biology 40, pp. 27-34. (10.1016/j.semcdb.2015.01.013)
- Welton, J. L., Webber, J. P., Botos, L., Jones, M. and Clayton, A. 2015. Ready-made chromatography columns for extracellular vesicle isolation from plasma. Journal of Extracellular Vesicles 4, article number: 27269. (10.3402/jev.v4.27269)
- Chowdhury, R., Webber, J. P., Gurney, M., Mason, M. D., Tabi, Z. and Clayton, A. 2015. Cancer exosomes trigger mesenchymal stem cell differentiation into pro-angiogenic and pro-invasive myofibroblasts. Oncotarget 6(2), pp. 715-731. (10.18632/oncotarget.2711)
- Webber, J. P. et al. 2015. Differentiation of tumour-promoting stromal myofibroblasts by cancer exosomes. Oncogene 34(3), pp. 290-302. (10.1038/onc.2013.560)
2014
- Spary, L. K., Salimu, J., Webber, J. P., Clayton, A., Mason, M. d. and Tabi, Z. 2014. Tumor stroma-derived factors skew monocyte to dendritic cell differentiation toward a suppressive CD14+PD-L1+phenotype in prostate cancer. OncoImmunology 3(9), article number: e955331. (10.4161/21624011.2014.955331)
- Webber, J. et al. 2014. Proteomics analysis of cancer exosomes using a novel modified aptamer-based array (SOMAscanTM) platform. Molecular and Cellular Proteomics 13(4), pp. 1050-1064. (10.1074/mcp.M113.032136)
2013
- Webber, J. P. and Clayton, A. 2013. How pure are your vesicles?. Journal of Extracellular Vesicles 2, article number: 19861. (10.3402/jev.v2i0.19861)
2012
- Shah, K. M. et al. 2012. Induction of microRNA resistance and secretion in differentiating human endometrial stromal cells [Letter]. Journal of Molecular Cell Biology 5(1), pp. 67-70. (10.1093/jmcb/mjs058)
2011
- Clayton, A., Al-Taei, S., Webber, J. P., Mason, M. D. and Tabi, Z. 2011. Cancer exosomes express CD39 and CD73, which suppress T cells through adenosine production. The Journal of Immunology 187(2), pp. 676-683. (10.4049/jimmunol.1003884)
- Michael, D. R. et al. 2011. The human hyaluronan synthase 2 (HAS2) gene and its natural antisense RNA exhibit coordinated expression in the renal proximal tubular epithelial cell. Journal of Biological Chemistry 286(22), pp. 19523-19532. (10.1074/jbc.M111.233916)
2010
- Webber, J. P., Steadman, R., Mason, M. D., Tabi, Z. and Clayton, A. 2010. Cancer exosomes trigger fibroblast to myofibroblast differentiation. Cancer Research 70(23), pp. 9621-9630. (10.1158/0008-5472.CAN-10-1722)
2009
- Zhang, L. et al. 2009. Thyrotropin receptor activation increases hyaluronan production in preadipocyte fibroblasts: Contributory role in hyaluronan accumulation in thyroid dysfunction. Journal of Biological Chemistry 284(39), pp. 26447-26455. (10.1074/jbc.M109.003616)
- Webber, J. P., Jenkins, R. H., Meran, S., Phillips, A. O. and Steadman, R. 2009. Modulation of TGFβ1-dependent myofibroblast differentiation by hyaluronan. American Journal of Pathology 175(1), pp. 148-160. (10.2353/ajpath.2009.080837)
- Webber, J. P., Meran, S., Steadman, R. and Phillips, A. O. 2009. Hyaluronan orchestrates transforming growth factor-β1-dependent maintenance of myofibroblast phenotype. Journal of Biological Chemistry 284(14), pp. 9083-9092. (10.1074/jbc.M806989200)
Teaching
College of Biomedical & Life Sciences
- Induction Course for GMO Workers - Microbiology Saftey
Undergraduate Teaching
- Intercalated & BSc Medical Pharamcology: Research supervisor to lab-based projects.
- Medic SSC Year 1: Tutorials and literature review
Postgraduate Teaching
PhD Supervisor:
- Miss Francesca Polveraccio [co-supervisors: Prof. A. Clayton & Prof. C. Emanuelli (University of Bristol)]
- Miss Sara Veiga [co-supervisor: Prof. A. Clayton]
Recently Completed PhD Candidates:
- Dr Vincent Yeung [Primary supervisor: Prof. A. Clayton]
Research Overview
As a member of the Exosome Biology Research Group, my research focuses on the role of cancer cell-derived exosomes in regulating mechanisms associated with tumour growth and progression. Exosomes are nanometre-sized vesicles that originate from the late endosomal pathway, and are therefore distinct from other extracellular vesicles. Not only have exosomes been shown to play an important role in cell-to-cell communication, but there is growing interest in the use of exosomes as disease biomarkers.
My specific research focuses on the role of prostate cancer exosomes in driving stromal cell differentiation. In patients with prostate cancer the prostatic stroma becomes aberrantly altered with an increased presence of cells with a myofibroblast-like phenotype. These cells are absent from normal tissues but are often associated with a fibrotic response whereby precursor cells, such as fibroblasts, undergo differentiation to become myofibroblastic. In various cancers, including prostate, the presence of myofibroblasts is associated with treatment resistant cancers and aggressive disease.
Classically myofibroblastic differentiation has been shown to occur in response to Transforming Growth Factor (TGF) beta1. We have demonstrated that exosomes can also drive differentiation in a TGFbeta1-dependent manner. The resulting myofibroblast-like phenotype is, however, distinct from that generated in response to soluble TGFbeta1. It is only through exosome-induced differentiation that we can make normal prostatic stromal cells mimic those found in disease. This difference in response is likely due to heparan sulphate proteoglycans (HSPGs) which play a key role in tethering TGFbeta1 to the exosome surface and therefore delivery to the target cell.
Funded by a Prostate Cancer UK Career Development Fellowship (2014 - 2019) I am currently investigating the role of HSPGs in exosome-driven stromal cell differentiation. In addition, I aim to determine whether exosomal-HSPGs can be used to distinguish patients with aggressive prostate cancer, therefore requiring treatment, from patients with indolent disease, for whom treatment would offer no benefit.
Specific Research Areas
- Mechanisms regulating exosome secretion
- Exosome-induced stromal cell differentiation.
- The role of heparan sulphate proteoglycans in regulating exosome function.
- Exosomes as biomarkers for prostate cancer.
Group Members
- Dr Alexandra Shephard (Post-doctoral Research Assistant)
- Miss Francesca Polveraccio (PhD Student; Co-supervised by Prof. A Clayton & Prof. C. Emanuelli)
- Miss Sara Veiga (PhD Student; Co-supervised by Prof. A. Clayton)
Alumni:
- Dr Vincent Yeung (Post-doctoral Research Assistant / PhD Student)
Grants held in last 5 years
- Tuberous Sclerosis Association (PhD Studentship). Characterising the role of exosomes in Tuberous Sclerosis Complex. £98K; 2018 - 2021 (Supervisors: Dr E Dunlop and Dr J Webber (Joint-PIs) and Dr A Tee (Co-I)).
- Wales Cancer Research Centre - ASTRA. NeoSTEM trial. Investigating stem cell gene expression panel to predict chemotherapy response in the neoadjuvant setting in Triple Negative Breast Cancer (TNBC). £13K; 2018 - 2020. (PI: Dr T Robinson; Co-Is: Dr J Webber, Prof R Butler, Prof M Smalley).
- MRC GW4 BioMed DTP (PhD Studentship). Stem cell exosomes: a system for initiating repair and regenertion in diverse disease settings. £100K; 2017 - 2020 (Supervisors: Dr J Webber (PI), Prof A Clayton (Co-I) and Prof C Emanuelli (Co-I; University of Bristol)).
- Cancer Research Wales (PhD Studentship). The role of heparan sulphate proteoglycans in exosome-mediated growth factor delivery & prostate tumour growth. £98K; 2017 - 2020 (Supervisors: Dr J Webber (PI) & Prof Aled Clayton (Co-I)).
- Welsh Crucible. Guided by the Sun: New cross-disciplinary methods for modelling and analysis of tumour growth. £8.7K; 2017 (Co-PIs: Dr J Webber & Dr E Dunlop; Co-Is: Dr J Giansiracusa, Dr H Morgan & Prof R Errington).
- Prostate Cancer UK - Career Development Fellowship. Exosomal heparan sulphate proteoglycans drive disease progression in patients with prostate cancer. £680K; 2014 - 2019 (PI: Dr J Webber).
- Life Sciences Research Netwrok Wales & Cardiff University (PhD Studentship). Role of exosomes in the progression of prostate cancer. £80K; 2014 - 2017 (Supervisors: Dr A Clayton (PI) & Dr J Webber (Co-I)).
- Prostate Cancer UK. Proteomics of human prostate cancer stroma. £44.5K; 2012 - 2014 (PI: Dr A Clayton; Co-Is: Dr J Webber & Dr I Brewis).