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Pancreatic Cancer - Stephen Thorpe

Stephen Thorpe - Pancreatic Cancer

Steven Thorpe

Name: Dr Stephen Thorpe

Job Title/Professional Qualifications: Ad Astra Fellow – Assistant Professor

Research keywords: Pancreatic cancer, model systems for cancer research, cell and tissue mechanics, mechanobiology, biomaterials, stem cells

Current research projects: The biophysical role of the tumour microenvironment in pancreatic cancer progression. PhD student: Michelle Fox. The role of syndecan-4 as a regulator of the tumour microenvironment in pancreatic cancer. PhD student: Leah Fallon. Diagnostic imaging of colorectal cancer - investigation of probe update mechanisms. PhD student: Anwesha Sarkar. Supervisors: Prof Ronan Cahill and Prof Donal O’Shea.

Contact details:
• Email: (opens in a new window)stephen.thorpe@ucd.ie
• Twitter: (opens in a new window)https://twitter.com/thorpesd
• LinkedIn: (opens in a new window)www.linkedin.com/in/stephendthorpe
• ORCID iD: https://orcid.org/0000-0002-4707-7756
• Web profile: (opens in a new window)https://people.ucd.ie/stephen.thorpe

Highlight Publication: Chronopoulos, A., Thorpe, S.D., Cortes, E., Lachowski, D., Rice, A.J., Mykuliak, V.V., Rog, T., Lee, D.A., Hytonen, V.P. and Del Rio Hernandez, A.E. (2020). "Syndecan-4 tunes cell mechanics by activating the kindlin-integrin-RhoA pathway" Nat Mater 19(6) 669-78 doi:10.1038/s41563-019-0567-1 (opens in a new window)https://www.nature.com/articles/s41563-019-0567-1.

Mechanical forces regulate fundamental aspects of cell behaviour in health and disease, from guiding stem cell differentiation to promoting cancer progression. Proteins on the cell surface called integrins clump together to form an adhesive bridge between the surrounding tissue matrix and the cell’s internal skeleton. These adhesions allow the cell to sense and respond to forces present in the tissue. However, there are other cell adhesion proteins that have not been widely studied.

Syndecan-4 is another adhesion protein present on all cells, which sticks to various components of the tissue matrix. To mimic tissue tension, we pulled on syndecan-4, which caused the cell to contract and stiffen. We then conducted biological experiments to define the mechanism through which syndecan-4 converts a mechanical force to a biochemical response.

What is the significance of this publication? Syndecan-4 is present on all cells and is expressed highly in some cancers. Many cancers are also much stiffer than the healthy tissue of origin. It is likely that syndecan-4 may dictate cell behaviour in these stiff environments. One such example is pancreatic cancer. In these studies, we used pancreatic stellate cells which are largely responsible for building the stiff pancreatic cancer tumour. By understanding the mechanism through which syndecan-4 senses tissue stiffness, we can potentially target this process using drugs to treat diseases such as pancreatic cancer.