Applications are invited from outstanding candidates to join a Cancer Research UK funded PhD programme at the Cancer Research UK Edinburgh Centre, part of the MRC Institute of Genetics and Molecular Medicine (IGMM) at the University of Edinburgh.
Colorectal cancer is the second commonest cause of cancer related mortality in the UK with the majority of deaths due to spread of the disease to other organs. A common feature of metastatic colorectal cancer is an elevated level of TGF-β signalling activity but how this signalling drives tumour spread is currently poorly understood1,2. TGF-β is a critical mediator of tissue homeostasis and a potent inducer of cell cycle arrest, differentiation and apoptosis. Together, these functions provide a key tumour suppressive function in numerous tissues. However, as cancers progress the role of TGF-β switches to that of a promoter of tumourigenesis and metastasis, a phenomenon known as the TGF-β paradox3. Understanding how TGF-β promotes tumour spread will provide critical insight into the mechanisms of colorectal cancer metastasis and help inform the development of new therapeutic strategies for its treatment.
The aim of this PhD project programme is to dissect the mechanisms driving the pro-tumourigenic and metastatic functions of TGF-β. The student will build upon previous work in the lab that has identified a number of potential mediators of TGF-β mediated tumour suppression to assess their potential function in promoting metastasis using 3D tumour organoids, mouse metastasis models and single cell transcriptomics4. A particular focus will be placed on how TGF-β signalling promotes immune evasion and induces changes within the tumour microenvironment and how this might be exploited therapeutically.
1. Guinney, J. et al. Nat Med 21, 1350-6 (2015). 2. Isella, C. et al. Nat Commun 8, 15107 (2017). 3. Massague, J. Cell 134, 215-30 (2008). 4. Tauriello, D.V.F. et al. Nature 554, 538-543 (2018).