2020-2022 Dr. Crudden is a Marie Skłodowska-Curie Postdoctoral Fellow. Her work is supported by EU funding: H2020 MSCA-IF-2018 Project #845391 (UNPACK PD-L1). You can keep up with the project and any arising publications on this page
Project Title: Molecular mechanism and inhibition of extracellular vesicle-mediated PD-L1 release in melanoma cells
Project Summary: Millions of tiny packages released from cells, full of ‘molecular mail’ are racing through your bloodstream right now, and they allow the cells of your body to work in harmony. However, when these packages (that we call exosomes), originate from cancer cells, they flood the body to promote a ‘pro-tumorigenic’ environment - helping the cancer survive, spread and resist effective therapy. I want to unravel the molecular machinery that cancer cells use to create these packages and send their manipulative messages, in order to learn how to stop this method of cancer communication, and slow disease progression. One of those manipulative messages they carry (called programmed-death ligand 1 or simply "PD-L1"), inactivates immune cell function that would otherwise recognize and kill the tumour. My project aimed to understand the molecular mechanism of how cancer cells can send out this particular immune-dampening message into circulation, and search for drugs that may be able to stop this process. The ultimate goal would be to develop new therapies that remove this blockade, restore the immune detection of the cancer, and thus limit the spread and progression of the disease.
Schematic adapted from Dassi et al. Nature Reviews Immunology 20, 209-215 (2020)