Dr Stephen Thorpe
BA, BAI, PDipStat, PhD, FHEA
I am interested in how physical signals impact cell function in health and disease. Biophysical or mechanical signals are transmitted through our tissues to our cells. Our cells sense these signals and respond. This process of mechanotransduction, the conversion of a physical signal into a biological response, is crucial to healthy development and is almost always a factor in disease progression. Whether this response is positive or negative depends on the nature of the cell's interaction with the tissue matrix, and the biophysical state of the cell, e.g. it's stiffness or contractility. My research is focussed on understanding how specific cell-matrix interactions mediate the transfer of physical signals from tissue to cell, and how the cell turns these biophysical signals into a biological response.
I implement a range of engineering and biological techniques to probe cellular processes in response to mechanical perturbation. In addition to enhancing our basic understanding of cell mechanobiology, my research looks to leverage this understanding to develop cartilage and bone tissue engineering and regenerative medicine strategies, and address the aberrant mechanobiology associated with one of the most lethal cancers, pancreatic ductal adenocarcinoma.
In relation to the cell's interaction with the tissue matrix, I have a particular interest in the role of the cell surface proteoglycan, syndecan, in mediating the biophysical response through its binding to specific tissue constituents. Biophysical signals ultimately result in changes in the genes that are expressed by the cell. I have a particular interest in the role of the nucleus as a sensor of mechanical stimuli, and modulator of mechano-responsive signalling.
Appropriate mechanotransduction is required for development of our tissues from their precursor stem cells. With the increasing use of stem cells in regenerative medicine therapies, my research focusses on using biophysical signals to better control stem cell differentiation, both in early development, and for the development of replacement connective tissues using adult mesenchymal stem cells.
Understanding how biophysical signals can be used to direct cell behaviour may aid us in treating many diseases for which aberrant mechanotransduction is a feature. Pancreatic ductal adenocarcinoma is one such disease, and is one of the most lethal cancers. It is associated with a dense and relatively stiff tumour-associated stromal tissue matrix which hampers attempts to treat this cancer. In collaboration with researchers at Barts Cancer Institute and Imperial College London, we are studying mechanotransduction of distinct tumour cell populations with a view toward directing cell forces to disrupt matrix organisation for the treatment of pancreatic cancer.
The aim of my research is to leverage fundamental mechanobiology knowledge to direct cell behaviour through specific cell-matrix interactions and biophysical stimulation for regenerative medicine and to disrupt aberrant mechano-signalling in disease.