My project aims to understand the mechanisms that drive the differentiation of fibroblast populations in solid tumours, i.e cancer-associated fibroblasts (CAFs) and 2) investigate the plasticity of CAF subtypes:

CAFs have vastly disparate (and sometimes opposing) functions on tumour progression, leaving the underlying mechanisms that drive their differentiation relatively unknown. We know that following infection or injury, fibroblasts swiftly undergo differentiation, driving fibrosis and tissue remodelling in cancer, and can change their immunomodulatory capacity. Additionally, a specialised subset of fibroblasts, fibroblastic reticular cells (FRCs), form the architecture of lymph nodes and are essential for immune responses. Here, they generate ECM conduits to facilitate immune cell trafficking, antigen presentation and effector lymphocyte activation, priming for an anti-tumour response. Therefore, fibroblast function can lead to both improved and poorer patient outcomes, depending on the specific fibroblast subset exhibited. If we can understand how different fibroblast subsets develop, proliferate or are recruited to solid tumours, we can attempt to shift the CAF subtypes to a more immunogenic phenotype, recruit more lymphocytes and immune cells and potentially bolster both our innate and immunotherapy-based anti-tumour immunity.