Research Projects

Many tumours secrete growth factors (GFs) to promote cellular proliferation, epithelial-mesenchymal transition, stromal reaction, and angiogenesis through autocrine and paracrine growth factor receptor (GFR) signalling. However, prevailing paradigms of natural killer (NK) cell receptor signalling dictate that ligands which are either shed or secreted from tumour cells bind to activating receptor and suppress NK cell effector functions. We were the first to show that platelet-derived growth factor (PDGF)-D can bind the NK cell immunoreceptor, NKp44, to induce NK cell anti-tumour immunity for control of tumour growth (Barrow et al. Cell, 2018). This work resulted in a change in the existing paradigm and shows that NK cells can sense changes in the cellular secretome to evoke anti-tumour immunity. Moreover, the results suggests that other innate receptors may sense secreted factors to induce immune responses. This project will focus on a combined approach of expressing recombinant vascular endothelial growth factor (VEGF) family proteins for biophysical studies and high-throughput screens to identify novel immunoreceptors that interact with the VEGF family members, and engineering chimeric antigen receptors (CAR) that are activated by VEGFs for cancer immunotherapy. The results will have relevance for cancer as well as infectious disease because many viruses encode growth factors that induce proliferative lesions to facilitate viral spread.

Contact project supervisor for further
information and application enquiries