Professor Robert Falconer

Robert’s interests are primarily focused on the tumour glycocalyx as a therapeutic target, and glycosyltransferases in particular, and in tumour protease-activated drug delivery. He is an experienced principal investigator and has secured funding from research councils and medical charities. He currently holds grants from Breast Cancer Now, Bone Cancer Research Trust, Incanthera plc, and co-leads a major £1.5m Yorkshire Cancer Research programme grant for cancer medicines discovery. He heads a team of 3 post-doctoral research assistants and 5 PhD students. He also leads the newly created Institute of Cancer Therapeutics Doctoral Training Centre (ICT DTC), established in 2019 following a major 10-year investment by Incanthera plc (£2m).  

Current Research Projects 

This research is focused on the design, synthesis and biological evaluation of inhibitors of polysialyltransferase (and prodrugs thereof) as a means by which to modulate tumour cell migration, invasion and metastasis. The polysialyltransferases are responsible for the tumour cell surface biosynthesis of polysialic acid (polySia), which plays a key role in the metastatic process in a number of cancers (see review: Curr. Cancer Drug Targets, 2012, 12, 925-939). We are employing computational methods to aid the inhibitor design process and have the capability to assess enzyme inhibition (see Carbohydrate Polymers, 2021, 259, 117741 and Analyst, 2020, 145. 4512-4521, ), cell-surface polySia decoration (see review: Carbohydrate Polymers, 2019, 224, 11545), and effects on cell-cell and cell-matrix adhesion, cell migration and invasion (see PLoS ONE, 2013, 8, e73366; Scientific Reports, 2016, 6, 33026; ChemBioChem, 2017, 18, 1332-1337). This work is currently supported by Yorkshire Cancer Research (programme grant), and the ICT Doctoral Training Centre.

This research is focused on the transformation of potent cytotoxic agents to inactive peptide-conjugates that are selectively activated within the tumour microenvironment, and is a strategic partnership with the DMPK group (Prof Paul Loadman) in the ICT. We are currently interested in the matrix metalloproteinases (MMPs) which are a family of endopeptidases overexpressed in tumours. We are employing both solution and solid phase chemistry to synthesise peptide-based therapeutics with potent but selective cytotoxicity in vivo. Compounds are assessed for in vitro cytotoxicity, successful cleavage in tumour tissue, stability in normal tissues (liver, kidney, lung) and plasma, before being evaluated in vivo (key collaboration with Dr Steve Shnyder, ICT). Our lead compound ICT2588 is currently progressing towards a Phase I clinical trial with Ellipses Pharma, having been licenced by Incanthera plc (see Cancer Research, 2010, 70, 6902-6912; Molecular Pharmaceutics, 2014, 11, 1294−1300). 

We are also collaborating with the Daldrup-Link group (Standford University, USA) to develop a novel theranostic, which has shown efficacy in breast cancer (see Small, 2014, 10, 566-575) and glioblastoma (see Molecular Cancer Therapeutics, 2017, 16, 1909-1921 and Nanotheranostics, 2019, 3, 299-310). Current projects are focused on development of treatments for breast cancer, prostate cancer and osteosarcoma. Our research is currently funded by Breast Cancer Now, Bone Cancer Research Trust, and the ICT Doctoral Training Centre.

PhD students: Katreen Banisalman; Athina Polykandritou (ICT DTC); Hannah Spencer (BCRT); Alexandra Serre (ICT DTC)

Post-Doctoral Researchers: Dr Francis Mprah Barnieh (YCR); Dr Goreti Ribeiro Morais (ICT DTC);

Intern (University of York): Mr Herbie Garland