Research
The Falconer group
is 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, and Incanthera plc. 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).
He has a keen interest and track
record in knowledge transfer and cancer drug development. As lead medicinal
chemist, he is co-founder and technology co-inventor of the ‘crocus smart-bomb’
(MMP-targeted anti-vascular agent ICT2588), which is being progressed to the
clinic by Ellipses Pharma/Incanthera Ltd. Incanthera is an ICT/University of
Bradford spin-out company (www.incanthera.com). He is co-inventor on four
patents associated with this technology.
Current Research Projects
1. Anti-cancer agents targeting
the tumour glycocalyx
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).
We are employing computational methods to aid the inhibitor design process and
have the capability to assess enzyme inhibition (see Carbohydrate Polymers,
2021 and Analyst, 2020), cell-surface polySia decoration
(see review: Carbohydrate Polymers, 2019), and effects
on cell-cell and cell-matrix adhesion, cell migration and invasion (see PLoS
ONE, 2013; Scientific Reports, 2016; ChemBioChem,
2017). This work is currently supported by a PhD studentship in the
ICT Doctoral Training Centre.
2. Endoprotease-activated
therapeutics
This research is focused on the
transformation of potent cytotoxic agents to inactive peptide-conjugates that
are selectively activated within the tumour microenvironment. We are currently
interested in the matrix metalloproteinases (MMPs) which are a family of
endopeptidases, and other endoporteases 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 (key
collaboration Prof Paul Loadman, Dr Huw Jones, ICT), before being evaluated in
vivo (key collaboration with Dr Steve Shnyder, ICT). We are additionally
pursuing prodrugs of DNA repair targets in collaboration with Prof Sherif
El-Khamisy (ICT & University of Sheffield). Our lead compound ICT2588 was
commercialised through Incanthera plc (see Cancer Research,
2010; Molecular Pharmaceutics, 2014).
We have a particular interest in osteosarcoma, and in developing kinder
treatments for this deadly disease that mainly affects children and young
adults. Funded by the Bone Cancer Research Trust (BCRT) through a PhD
studentship (2018-22), and a project grant (2023-26), our aim is to achieve
preclinical proof-of-concept for an MMP-activated tumour-targeted prodrug of
methotrexate. We will evaluate our lead molecules in clinically-relevant
orthotopic models of the disease in collaboration with Prof Allie Gartland
(University of Sheffield).
A project focused on
neuroblastoma, and targeted delivery of an inhibitor of DNA repair is being funded
by Worldwide Cancer Research (2023-25). Funding to explore clinically-relevant
combinations of a lead prodrug has been secured from Neuroblastoma UK (2025-28).
In collaboration with Dr Francis Barnieh (Research Fellow), we have explored
CD13 as a new target for peptide conjugate delivery (see iScience 2023,
BBA Reviews of Cancer 2021).
We continue our long-standing collaboratiion with the Daldrup-Link group
(Standford University, USA) to further develop a novel theranostics, which have
shown efficacy in breast cancer (see Small 2014) and
glioblastoma (see Molecular Cancer Therapeutics 2017, Nanotheranostics
2019, Nanoscale, 2025, and Scientific Reports, 2025).
Current projects are additionally focused on development of treatments for
breast cancer, prostate cancer and neuroblastoma. Our research is currently
funded by Bone Cancer Research Trust, Worldwide Cancer Research, Neuroblastoma
UK, the ICT Doctoral Training Centre, and the Masonic Charitable Foundation.
Current Team members
PhD students
Ann Kengkwasingh (Personal Scholarship
2024-28)
Gabriel Nwokolo (Masonic
Charitable Foundation 2024-28)
Zubeda Khatoon (ICT DTC 2022-26)
Post-Doctoral Researchers
Dr Hannah Spencer (BCRT
2023-26)
Dr April Baral (Worldwide
Cancer Research 2023-25; Neuroblastoma UK 2025-27)
Researcher Lecturer
Dr Goreti Ribeiro Morais (ICT
DTC)
Interns and Project students
Cora Costello (University of
York internship; 2024-25)
Fatima Aslam (MRes Drug
Development; 2024-25)
Mollie Browes (MRes Drug
Development; 2024-25)