Dr Alan Serrels
The tumour is a complex ‘organ’ consisting of many cell types that interact to support tumour growth and drive metastasis. Within this complex microenvironment immune cells play an important role and have been shown to contribute to tumour growth, angiogenesis, intravasation, and metastasis, while also contributing to suppression of the anti-tumour immune response. In part, tumour cells themselves orchestrate the complexity of the microenvironment, as they secrete a variety of factors that not only recruit immune cells but also reprogram these to support the needs of the tumour as it grows. We have recently identified a role for integrin signalling, and more specifically the non-receptor protein tyrosine kinase Focal Adhesion Kinase (FAK) in regulating signalling between tumour cells and their surrounding environment.
In order to try and understanding how tumour cells interact with their surrounding microenvironment and better characterize the role of integrin signalling in this context, we use intra-vital imaging to see with great detail phenotypic changes in both tumour cell behaviour and the microenvironment when we perturb signalling either through mutagenesis, gene knockout, or treatment with pharmacological inhibitors. Using advanced microscopy techniques such as confocal, multi-photon, FLIM, FRAP, photo-activation, photo-switching, and vibrational spectroscopy, we have performed ‘in vivo phenotypic profiling’ of the role of FAK in cancer biology, and in collaboration with the labs of Professor Margaret Frame and Dr Bryan Serrels are using pathway analysis and proteomics to interrogate the signalling underlying these phenotypes in order to identify new therapeutic targets.
Continued development and application of advanced microscopy techniques to in vivo cancer research is a key aim of our lab as we aim to derive a greater degree of information from a single sample. In search of this goal we have recently built and continue to develop (in collaboration with Dr Andy Downes) a bespoke multi-modal microscope that combines two-photon fluorescence and Fluorescence Lifetime Imaging (FLIM), with label-free imaging modalities including Second Harmonic Generation (SHG), Coherent Anti-stokes Raman Scattering (CARS), and Stimulated Raman Scattering (SRS). This combinatorial approach offers great benefits over using just confocal or multi-photon microscopy on their own, by adding a greater degree of context and understanding to the image. In addition, the potential to use CARS and SRS for imaging anti-cancer drugs is still under investigation, and is the focus of a collaboration with the labs of Professor Margaret Frame, Professor Val Brunton, and Dr Alison Hulme.
University of Edinburgh:
- Professor Margaret Frame
- Professor Val Brunton
- Dr Bryan Serrels
- Dr You-Ying Chau / Professor Nick Hastie
- Dr Neil Henderson
University of Glasgow:
- Professor Rob Nibbs