Polysialyltransferases as a target in metastatic cancer

Polysialic acid plays an essential role in neuronal development, but by adulthood is absent from the human body. Its biosynthesis is regulated by two polysialyltransferases. Polysialic acid is aberrantly re-expressed on the surface of many tumours, where it plays a key role in diseases progression and metastasis. It is therefore an attractive anti-cancer target (see Current Cancer Drug Targets, 2012, 12, 925-939).

The ICT is focused on the development of novel polysialyltransferase inhibitors, using computational chemistry to aid compound design. We have developed assays to assess compound inhibition (see Analyst, 2016, 141, 5849-5856) and have utilized tool compounds to show the potential of the approach (see PLoS ONE, 2013, 8, e73366). We additionally have explored the role of polySia expression in hypoxia, a characteristic common to solid tumours (see Scientific Reports, 2016, 6, 33026; ChemBioChem, 2017, 18, 1332-1337). The wider project benefits from funding from programme funding from Yorkshire Cancer Research and more recently from the Wellcome Trust. The student will join a successful, motivated multidisciplinary team with expertise in medicinal chemistry, pharmacology, immunohistochemistry and drug analysis.

This project will focus on the biological evaluation of potential polysialyltransferase inhibitors, utilising in vitro assays to assess compound inhibition, and techniques to assess effects of compounds on cell adhesion, migration, and invasion.