Dr Toby Phesse

Senior Lecturer

School of Biosciences

: Available for postgraduate supervision

My research is interested in how cell signalling regulates cell function in normal tissue, stem cells and tumours to gain insight into how cancer is initiated, grows and metastasises. We then use this information to identify novel targets and strategies to treat various cancers, with a focus on the Wnt signalling pathway and gastrointestinal and prostate.

We aim to employ a bench-to-bedside approach in which applied research in preclinical models using genetic and molecular techniques is complimented with pharmacological strategies with our industrial and clinical collaborators thus enabling translation to potential clinical applications and ultimately improving patient health.

Current lab members:

Dr Hector Arredondo (Post Doc)

Kieran Hodson (PhD student)

Jess Hembrough (PhD Student)

Date
Type

2020

Jardé, T. et al. 2020. Mesenchymal niche-derived neuregulin-1 drives intestinal stem cell proliferation and regeneration of damaged epithelium. Cell Stem Cell 27(4), pp. 646-662.E7., article number: VOLUME 27, ISSUE 4, P646-662.E7, OCTOBER 01, 2020. (10.1016/j.stem.2020.06.021)
Tran, B. M. et al. 2020. The hepatitis B virus pre-core protein p22 activates Wnt sgnaling. Cancers 12(6), article number: 1435. (10.3390/cancers12061435)
Koushyar, S., Powell, A. G., Vincan, E. and Phesse, T. J. 2020. Targeting Wnt signaling for the treatment of gastric cancer. International Journal of Molecular Sciences 21(11), article number: 3927. (10.3390/ijms21113927)

2019

Flanagan, D. J., Vincan, E. and Phesse, T. J. 2019. Wnt signaling in cancer: not a binary ON:OFF switch. Cancer Research (10.1158/0008-5472.CAN-19-1362)
Parry, L. and Phesse, T. J. 2019. FXR regulates intestinal stem cells response to bile acids in a high fat diet. Biotarget 3(12) (10.21037/biotarget.2019.07.01)
Flanagan, D., Barker, N., Ernst, M., Vincan, E. and Phesse, T. 2019. The function of Lgr5+ cells in the gastric antrum does not require Fzd7 or Myc in vivo. Biomedicines 7(3), article number: 50. (10.3390/biomedicines7030050)
Flanagan, D. J. et al. 2019. Frizzled-7 is required for Wnt signaling in gastric tumours with and without Apc mutations. Cancer Research 79(5), pp. 970-981. (10.1158/0008-5472.CAN-18-2095)
Eissman, M. F. et al. 2019. IL-33 mediated mast cell activation promotes gastric cancer through macrophage mobilization. Nature Communications 10, article number: 2735. (10.1038/s41467-019-10676-1)

2018

Greenow, K. R., Zverev, M., May, S., Kendrick, H., Williams, G. T., Phesse, T. and Parry, L. 2018. Lect2 deficiency is characterised by altered cytokine levels and promotion of intestinal tumourigenesis. Oncotarget 9(92), pp. 36430-36443. (10.18632/oncotarget.26335)
May, S. et al. 2018. Mbd2 enables tumourigenesis within the intestine while preventing tumour-promoting inflammation. Journal of Pathology 245(3), pp. 270-282. (10.1002/path.5074)
Pearson, H. B. et al. 2018. Identification of Pik3ca mutation as a genetic driver of prostate cancer that cooperates with Pten loss to accelerate progression and castration-resistant growth. Cancer Discovery 8(6), pp. 764-779. (10.1158/2159-8290.CD-17-0867)
Flanagan, D., Austin, C., Vincan, E. and Phesse, T. 2018. Wnt Signalling in gastrointestinal epithelial stem cells. Genes 9(4), article number: 178. (10.3390/genes9040178)
Vincan, E., Schwab, R. H., Flanagan, D. J., Moselen, J. M., Tran, B. M., Barker, N. and Phesse, T. 2018. The central role of Wnt signaling and organoid technology in personalizing anticancer therapy. Progress in Molecular Biology and Translational Science 153, pp. 299-319. (10.1016/bs.pmbts.2017.11.009)

2017

Phesse, T., Marsh Durban, V. and Sansom, O. J. 2017. Defining key concepts of intestinal and epithelial cancer biology through the use of mouse models. Carcinogenesis 38(10), pp. 953-965. (10.1093/carcin/bgx080)
Flanagan, D. J., Barker, N., Nowell, C., Clevers, H., Ernst, M., Phesse, T. J. and Vincan, E. 2017. Loss of the Wnt receptor frizzled 7 in the mouse gastric epithelium is deleterious and triggers rapid repopulation in vivo. Disease Models and Mechanisms 10(8), pp. 971-980. (10.1242/dmm.029876)
Phesse, T. J. and Sansom, O. J. 2017. Lgr5 joins the club of gastric stem cell markers in the corpus. Nature Cell Biology 19(7), pp. 752-754. (10.1038/ncb3567)
Flanagan, D. J., Vincan, E. and Phesse, T. J. 2017. Winding back Wnt signalling: potential therapeutic targets for treating gastric cancers. British Journal of Pharmacology 174(24), pp. 4666-4683. (10.1111/bph.13890)
Schwab, R. . H., Amin, N., Flanagan, D. J., Johanson, T. M., Phesse, T. and Vincan, E. 2017. Wnt is necessary for mesenchymal to epithelial transition in colorectal cancer cells. Developmental Dynamics 247(3), pp. 521-530. (10.1002/dvdy.24527)

2016

Flanagan, D. J., Schwab, R. H. M., Tran, B. M., Phesse, T. J. and Vincan, E. 2016. Isolation and culture of adult intestinal, gastric, and lver organoids for cre-recombinase-mediated gene deletion. In: Methods in Molecular Biology. Humana Press, pp. 1-11., (10.1007/7651_2016_14)
Togel, L. et al. 2016. Dual targeting of Bromodomain and Extraterminal Domain Proteins, and WNT or MAPK Signaling, Inhibits c-MYC Expression and Proliferation of Colorectal Cancer Cells. Molecular Cancer Therapeutics 15(6), pp. 1217-1226. (10.1158/1535-7163.MCT-15-0724)
Phesse, T., Flanagan, D. and Vincan, E. 2016. Frizzled7: a promising achilles' heel for targeting the Wnt receptor complex to treat cancer. Cancers 8(5), pp. 50. (10.3390/cancers8050050)

2015

Pearson, H. B. et al. 2015. The polarity protein Scrib mediates epidermal development and exerts a tumor suppressive function during skin carcinogenesis. Molecular Cancer 14, article number: 169. (10.1186/s12943-015-0440-z)
Flanagan, D. et al. 2015. Frizzled7 functions as a Wnt receptor in intestinal epithelial Lgr5+ stem cells. Stem Cell Reports 4(5), pp. 759-767. (10.1016/j.stemcr.2015.03.003)

2014

Elsum, I. A. et al. 2014. Scrib heterozygosity predisposes to lung cancer and cooperates with KRas hyperactivation to accelerate lung cancer progression in vivo. Oncogene 33(48), pp. 5523-5533. (10.1038/onc.2013.498)
Phesse, T. J. et al. 2014. Partial inhibition of gp130-Jak-Stat3 signaling prevents Wnt–β-catenin–mediated intestinal tumor growth and regeneration. Science Signaling 7(345), article number: ra92. (10.1126/scisignal.2005411)
Infantino, S. et al. 2014. The tyrosine kinase Lyn limits the cytokine responsiveness of plasma cells to restrict their accumulation in mice. Science Signaling 7(338), pp. ra77. (10.1126/scisignal.2005105)
Phesse, T. J. et al. 2014. Endogenous c-Myc is essential for p53-induced apoptosis in response to DNA damage in vivo. Cell Death and Differentiation 21(6), pp. 956-966. (10.1038/cdd.2014.15)
Rickard, J. et al. 2014. RIPK1 regulates RIPK3-MLKL-driven systemic inflammation and emergency hematopoiesis. Cell 157(5), pp. 1175-1188. (10.1016/j.cell.2014.04.019)
Hare, L. et al. 2014. Physiological expression of the PI3K-activating mutationPik3caH1047Rcombines withApcloss to promote development of invasive intestinal adenocarcinomas in mice. Biochemical Journal 458(2), pp. 251-258. (10.1042/BJ20131412)
Stuart, E. et al. 2014. Therapeutic inhibition of jak activity inhibits progression of gastrointestinal tumors in mice. Molecular Cancer Therapeutics 13(2), pp. 468. (10.1158/1535-7163.MCT-13-0583-T)

2013

Phesse, T. and Sansom, O. J. 2013. Responding to R-spondin: slit2 potentiates intestinal regeneration. Cell Stem Cell 13, pp. 512-514. (10.1016/j.stem.2013.10.006)
Meniel, V. et al. 2013. Cited1 deficiency suppresses intestinal tumorigenesis. PLoS Genetics 9(8), article number: e1003638. (10.1371/journal.pgen.1003638)

2011

Sakthianandeswaren, A. et al. 2011. PHLDA1 expression marks the putative epithelial stem cells and contributes to intestinal tumorigenesis. Cancer Research 71(10), pp. 3709-3719. (10.1158/0008-5472.CAN-10-2342)

2010

Ashton, G. H. et al. 2010. Focal adhesion kinase is required for intestinal regeneration and tumorigenesis downstream of Wnt/c-Myc signaling. Developmental Cell 19(2), pp. 259-269. (10.1016/j.devcel.2010.07.015)

2009

Burke, Z. D., Reed, K. R., Phesse, T., Sansom, O. J., Clarke, A. R. and Tosh, D. 2009. Liver zonation occurs through a β-catenin–dependent, c-Myc–independent mechanism. Gastroenterology 136(7), pp. 2316-2324. (10.1053/j.gastro.2009.02.063)
Pearson, H. B., Phesse, T. and Clarke, A. R. 2009. K-ras and Wnt signaling synergize to accelerate prostate tumorigenesis in the mouse. Cancer Research 69(1), pp. 94-101., article number: http://dx.doi.org/10.1158/0008-5472.CAN-08-2895. (10.1158/0008-5472.CAN-08-2895)
Phesse, T. and Clarke, A. R. 2009. Normal stem cells in cancer prone epithelial tissues. British Journal of Cancer 100(2), pp. 221-227. (10.1038/sj.bjc.6604850)
Bollrath, J. et al. 2009. gp130-mediated Stat3 activation in enterocytes regulates cell survival and cell-cycle progression during colitis-associated tumorigenesis. Cancer Cell 15(2), pp. 91-102. (10.1016/j.ccr.2009.01.002)

2008

Phesse, T., Parry, L., Reed, K. R., Ewan, K. B. R., Dale, T. C., Sansom, O. J. and Clarke, A. R. 2008. Deficiency of Mbd2 attenuates Wnt induced tumourigenesis via deregulation of a novel Wnt inhibitor, Lect.2. Molecular and Cellular Biology 28(19), pp. 6094-6103. (10.1128/MCB.00539-08)

2007

Sansom, O. J. et al. 2007. Myc deletion rescues Apc deficiency in the small intestine. Nature 446(7136), pp. 676-679. (10.1038/nature05674)

2006

Muncan, V. et al. 2006. Rapid loss of intestinal crypts upon conditional deletion of the Wnt/Tcf-4 target gene c-Myc. Molecular and Cellular Biology 26(22), pp. 8418-8426. (10.1128/MCB.00821-06)

My primary research interest is in understanding how cell signalling controls homeostasis, regeneration, stem cell function and disease, with a focus on Wnt signalling in the gastrointestinal tract. Many of the cell signalling pathways that are critical for embryonic development, homeostasis and regeneration of epithelial tissues are deregulated during disease, and in particular cancer. Thus, by understanding the molecular events that regulate cell signalling during these biological processes, and the aberrations that result in deregulation and disease, we aim to identify novel therapeutic strategies.

My lab uses a combination of advanced in vitro techniques, such as organoid cultures (Fig. 1), together with sophisticated mouse models (Fig. 2), to gain new insights into the requirement for cell signalling during the biology of the adult gastrointestinal epithelium, and thus understand how deregulated signalling results in disease.

Stem cells are intimately associated with cancer, as they have frequently been demonstrated to be the cell of origin for several different cancers including the intestine. The discovery of Lgr5 as a marker of intestinal stem cells has provided a powerful research tool to enable further insight into the biology of the intestine and the role of stem cells in cancer. Indeed, Lgr5 also marks a population of cancer stem cells which is able to provide the proliferative and self-renewal properties of intestinal tumours. Thus, understanding what regulates stem cells is a major interest in the field and our lab is particularly interested in the role of Wnt signalling.

Although the Wnt pathway is deregulated in around 85% of colon tumours it is also required, at lower levels, for the normal homeostatic function of the intestine, and during regeneration. The cytoplasmic signal transducers involved in Wnt signalling have been well characterised, and current research continues to gain new insights into its complexity and interaction with other pathways (Bollrath and Phesse et al, Cancer Cell, 2009 and Phesse et al, Science Signalling, 2014). Compared to the cytoplasmic Wnt regulators, the Wnt receptor complex is relatively poorly understood. Indeed, it is still not fully documented which of the 10 mammalian Frizzled Wnt receptors bind to which of the 19 mammalian Wnt ligands. It was only in 2015 that we demonstrated that Frizzled7 is the predominant Wnt receptor required for intestinal and gastric stem cell function (Flanagan and Phesse et al, Stem Cell Reports, 2015,reviewed in Phesse et al, Cancers, 2016 and Flanagan et al., DMM, 2017), and current projects are investigating the role of this receptor in other organs and disease settings including targeting Wnt signalling in metastatic prostate cancer.

Key Collaborators

Professor Owen Sansom – Beatson CRUK, Scotland

Professor Elizabeth Vincan – University of Melbourne, Australia

Professor Nick Barker – AStar Institute, Singapore

I give lectures, workshops and tutorials in several subjects including, molecular biology, cell biology, cancer therapy and stem cells.

I currently teach in the following modules at Cardiff: Molecular Biology of the Gene (BI2234), Contemporary Topics in Disease (BI3351), Cancer: Cellular and Molecular Mechanisms and Therapeutics (BI3352), and assess work in Concepts of Disease (BI2332).

I am lead the academic assessment lead for Molecular Biology of the Gene (BI2234).

I am a Fellow of the Higher Education Academy (FHEA), and approach an engaging, interactive approach to all my teaching.

Dr Phesse was awarded his PhD from the University of Warwick where he studied the co-operation between Wnt signalling and TGF-β signalling during embryonic development. It was during this project that he learned of the important role that Wnt signalling played during cancer, and subsequently secured a post-doc position in the laboratory of Professor Alan Clarke at Cardiff University. It was in Alan’s lab that he cultivated his primary research interest, studying how cell signalling regulates homeostasis, stem cell function, regeneration and cancer. His work has focused mainly on the Wnt signalling pathway and the gastrointestinal tract, although he has also investigated other organs including the liver, prostate and skin, with the underlying goal of identifying novel therapeutic strategies for the treatment of cancer.

After three successful years with Alan, Toby obtained a Fellowship from the British Council to work at the Ludwig Institute in Melbourne to study the interaction between Wnt signalling and gp130/Stat3 signalling in GI cancer. He published this work in Cancer Cell in 2009 which has since been cited over 700 times. He subsequently maintained continuous National Health Medical Research Council funding for the following 6 years which enabled him to manage a small research group in a variety of institutes, including the prestigious Walter and Eliza Hall Institute and the University of Melbourne, studying the role of cell signalling in regeneration and cancer.

In 2016 he was appointed Senior Research Fellow and co-lab head at the University of Melbourne, before being awarded additional UK based fellowships (Wellcome Trust and Cardiff University) to facilitate his move back to Cardiff as a Fellow at the new established European Cancer Stem Cell Research Institute at Cardiff University. In 2019 he was appointed Senior Research Fellow, and in 2021 Lecturer, and Senior Lecturer in 2023.

He has an ongoing position at University of Melbourne as an Honorary Senior Fellow, maintaining close links there with co-funding and close research interests with colleagues there.

Honours and awards

Honorary Senior Fellow at University of Melbourne, Australia.

Professional memberships

Fellow of the Higher Education Academy

Academic positions

2023-present	Senior Lecturer, European Cancer Stem Cell Research Institute, Cardiff University.
2021- 2023	Lecturer, European Cancer Stem Cell Research Institute, Cardiff University.
2018 – present	Tenured Senior Fellow in European Cancer Stem Cell Research Institute, Cardiff University.
2016 - present	Group Leader Research Fellow in European Cancer Stem Cell Research Institute, Cardiff University.
2016 - present	Honorary Senior Fellow, Doherty Institute, University of Melbourne, Australia.
2016	Co-lab Head with Prof. Vincan, Doherty Institute, University of Melbourne, Australia.
2012 – 2015	Senior Postdoctoral Fellow at The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
2008 - 2012	Senior Postdoctoral Fellow at The Ludwig Institute of Cancer Research Ltd. in the laboratory of Professor Matthias Ernst, Melbourne, Australia.
2008 - 2012	Honorary Fellow of The University of Melbourne, Department of Surgery and Department of Medical Biology, Australia, Melbourne.
2004 - 2008	Postdoctor at Cardiff University, UK in the laboratory of Professor Alan Clarke.

Speaking engagements

Keynote Speaker at inaugural WntUK COnference, London, 2024.

Committees and reviewing

Grant Reviewer for MRC, BBSRC, NHMRC (Aus), Worldwide Cancer Research, British Skin Foundation, Bowel Research UK, Leverhulme Trust, and Tel-Aviv University.

Journal Reviewer for many journals including Nature, Nat Cell Biol, EMBO Reports, Oncogene, Carcinogenesis and DMM.

Internal REF2021 and REF2028 Review panel member.

Chair for the European Cancer Stem Cell Research Institute Grants Committee.

Panel member for the Athena Swann Advisory board on Parents and Carers.

I am interested in supervising PhD students in the areas of:

Wnt signalling
Gastrointestinal cancer
Prostate cancer
Cholangiocarcinoma
Virotherapy for cancer

Current supervision

Kieran Hodson

Research student

The lab has engaged with the public and scientific collegues on many platforms including conferences, Webinares with patient groups, and videos published on the University Websites:

Virtual lab tour and patient engagement organised by Prostate Cancer Research charity in which I presented our research on prostate cancer and engaged in open discussion with prostate cancer patients/families and carers, 2021.
Webpage on PCR website dedicated to our project targeting Wnt signalling prostate cancer.
Host for student nurses from Cardiff and Vale UHW as part of their training.
Panel judge and cancer expert for JamtheMess computer game competition to create educational digital games regarding cancer treatment and cancer biology.
Mentor for a student on the GOWALES platform for underprivileged or disabled students which involves several meetings with a specific student matched to my profile in which I provide career guidance and answer any questions about the mechanisms of cancer research and also act as a network hub ‘first contact’ for the student to help promote opportunities after graduation.

Interviews and news:

Podcast on the Prostate Pod (https://open.spotify.com/show/1ZSRsZSrqsuxHc3yiK1Yn8)
Live interview on BBC Science Café Radio show.
Live interviews on national radio in Australia and New Zealand.
Videos on the AMMF Cholangiocarcinoma Charity website and Institute website to promote World Cholangiocarcinoma Day.
Interview for Oncology Learning Network website.
Invited speaker at many international and national conferences and seminars.

Contact Details

PhesseT@cardiff.ac.uk
+44 29206 88495
Hadyn Ellis Building, Maindy Road, Cardiff, CF24 4HQ

Research themes

Specialisms

Cancer cell biology
Cancer therapy
Stem cells

Researchers to investigate new drug to stop incurable prostate cancer spread