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Toby Phesse

Dr Toby Phesse

Senior Lecturer

School of Biosciences

Email
PhesseT@cardiff.ac.uk
Telephone
+44 29206 88495
Campuses
Hadyn Ellis Building, Maindy Road, Cardiff, CF24 4HQ
Users
Available for postgraduate supervision

Overview

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 Valerie Meniel (Post Doc)

Dr Hector Arredondo (Post Doc)

Kieran Hodson (PhD student)

Publication

2022

2021

2020

2019

2018

2017

2016

2015

2014

2013

2011

2010

2009

2008

2007

2006

Articles

Book sections

Research

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

Teaching

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.

Biography

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.

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.

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. 

Supervisions

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

Kieran Hodson

Research student

Engagement

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.