Robert Falconer
Reader in Medicinal Chemistry
| Faculty/Dept/School |
School of Pharmacy and Medical Sciences (Faculty of Life Sciences) |
|---|---|
| r.a.falconer1@bradford.ac.uk | |
| Telephone | +441274 235842 |
Biography
Dr Robert Falconer graduated with first-class honours in pharmacy from The School of Pharmacy, University of London (now UCL School of Pharmacy), and undertook his pre-registration pharmacy training year at Joyce Green Hospital, Dartford. A brief stint as Staff Pharmacist following registration preceded a return to academia in London, where he undertook a PhD in medicinal chemistry. He was subsequently appointed Lecturer in Pharmaceutical Sciences.
A move to the new Institute of Cancer Therapeutics (ICT), University of Bradford followed, to establish one of three new medicinal chemistry teams there. Now as Reader in Medicinal Chemistry, he is an academic responsible primarily for research, but also research-informed teaching (primarily the ICT’s post-graduate MSc courses) and the training of research students. He has served as Deputy Director of the ICT since Feb 2017, overseeing medicinal chemistry and drug discovery. He is a member of several professional and learned societies, notably the Royal Pharmaceutical Society and is a registered pharmacist with the General Pharmaceutical Council. As a Fellow of the Royal Society of Chemistry, he has previously served as Honorary Treasurer for the RSC Central Yorkshire Local Section Trust (2012-18).
Research
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, and Incanthera Ltd, and co-leads a major £1.5m Yorkshire Cancer Research programme grant for cancer medicines discovery, and heads a team of 3 post-doctoral research assistants and 6 PhD students. He also leads the newly created Institute of Cancer Therapeutics Doctoral Training Centre, established in 2019 following a major 10-year investment by Incanthera Ltd (£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
My research is focused on the design, synthesis and biological evaluation of inhibitors of polysialyltransferase 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, cell-surface polySia decoration, and effects on cell-cell and cell-matrix adhesion, cell migration and invasion. This work is currently supported by Yorkshire Cancer Research (programme grant), Neuroblastoma UK, and the ICT Doctoral Training Centre.
2. Endoprotease-activated therapeutics
My 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 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. We are also collaborating with the Daldrup-Link group (Standford University, USA) to develop a novel theranostic, which has shown efficacy in 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.
| Contract Researchers | |
|---|---|
| Name | Dr Xiaoxiao Guo |
| Role | Postdoctoral Researcher |
| Project | Yorkshire Cancer Research |
| Duration | 5 years |
| Name | Dr Goreti Morais |
| Role | Postdoctoral Researcher |
| Project | ICT Doctoral Training Centre |
| Duration | 10 years |
| Name | Dr David Pajtas |
| Role | Postdoctoral Researcher |
| Project | Breast Cancer Now |
| Duration | 2 years |
Professional activities
- 01-SEP-13: University of Bradford - Reader in Medicinal Chemistry
- 01-OCT-05: University of Bradford - Lecturer in Medicinal Chemistry
- 01-JUN-03: UCL School of Pharmacy - Lecturer in Pharmaceutical Sciences
- 01-OCT-00: UCL School of Pharmacy - Research & Teaching Fellow
- 01-MAR-12: Royal Society of Chemistry Central Yorkshire Section,
- 01-APR-16: Kidscan Scientific Advisory Board ,
- 01-JAN-16: Neuroblastoma UK Scientific Advisory Board,
- 01-JAN-18: Scientific Advisory Board, Medical Research Charity Group/ Health Research Board Ireland Joint Funding Committee ,
- 01-MAR-08: Royal Society of Chemistry Central Yorkshire Section,
- 01-JAN-97: Dartford & Gravesham NHS Trust - MRPharmS
- 01-JAN-96: University of London, School of Pharmacy - BPharm (Hons)
- 01-JAN-00: University of London, School of Pharmacy - PhD
- 01-JAN-17: - Vice-Chancellor's Award for Excellence
- Fellow, Royal Society of Chemistry
- Member, British Association for Cancer Research
- Member, European Association for Cancer Research
- Member, Amercian Association for Cancer Research
- Member, Royal Society of Chemistry
- Member, Royal Pharmaceutical Society / General Pharmaceutical Council
Publications
| Peer Reviewed Journal | |
|---|---|
| Title | Theranostic nanoparticles enhance the response of glioblastomas to radiation (2019) |
| Authors | Wu, W.; Klockow, J.L.; Mohanty, S.; Wu, W.; Aghighi, M; Melemenidis, S.; Chen, Z.; Li, K.; Ribeiro Morais, G.; Jurgen, S.; Graves, E.E.; Rao, J.; Loadman, P.M.; Falconer, R.A.; Mukherjee, S.; Chin, F.T.; Daldrup-Link, H. |
| Journal | Nanotheranostics |
| DOI | doi:10.7150/ntno.35342 |
| Title | Novel Ran-RCC1 Inhibitory Peptide-Loaded Nanoparticles Have Anti-Cancer Efficacy In Vitro and In Vivo (2019) |
| Authors | Yusuf A. Haggag;Kyle B. Matchett;Robert Falconer;mohammad isreb;Jason Jones;Ahmed Faheem;Paul McCarron;Mohamed El-Tanani; |
| Journal | Cancers |
| DOI | 10.3390/cancers11020222 |
| Title | Recent advances in the analysis of polysialic acid from complex biological systems (2019) |
| Authors | Guo, Xiaoxiao; Elkashelf, Sara M.; Loadman, Paul M.; Patterson, Laurence H.; Falconer, Robert A. |
| Journal | Carbohydrate Polymers |
| DOI | https://doi.org/10.1016/j.carbpol.2019.115145 |
| Title | A novel theranostic strategy for MMP-14 expressing glioblastomas impacts survival. (2017) |
| Authors | Mohanty, S.; Chen, Z.; Li, K.; Ribeiro Morais, G.; Klockow, J.; Yerneni, K.; Pisani, L.; Chin, F.T.; Mitra, S.; Cheshier, S.; Chang, E.; Gambhir, S.S.; Rao, J.; Loadman, P.M.; Falconer, R.A.; Daldrup-Link, H.E. |
| Journal | Molecular Cancer Therapeutics |
| DOI | 10.1021/mp400760b |
| Title | Membrane-type matrix metalloproteinases (MT-MMPs): expression, roles in metastatic prostate cancer progression and opportunities for drug targeting (2017) |
| Authors | Falconer, R.A.; Loadman, P.M. |
| Journal | Journal of Cancer Metastasis and Treatment |
| DOI | DOI: 10.20517/2394-4722.2017.40 |
| Title | Rationalized Computer-Aided Design of Matrix-Metalloprotease-Selective Prodrugs (2017) |
| Authors | Jain, M.; Harburn, J.J.; Gill, Jason H.; Loadman, Paul M.; Falconer, Robert A.; Mooney, C.A.; Cobb, S.L.; Berry, David J. |
| Journal | Journal of Medicinal Chemistry |
| DOI | http://dx.doi.org/10.1021/acs.jmedchem.6b01472 |
| Title | Exploring and Exploiting Acceptor Preferences of the Human Polysialyltransferases as a Basis for an Inhibitor Screen (2017) |
| Authors | Ehrit, J.; Keys, T.G.; Sutherland, Mark H.; Wolf, S.; Meier, C.; Falconer, Robert A.; Gerardy-Schahn, R. |
| Journal | ChemBioChem |
| DOI | http://dx.doi.org/10.1002/cbic.201700157 |
| Title | Polysialic acid sustains cancer cell survival and migratory capacity in a hypoxic environment (2016) |
| Authors | Elkashef, Sara M.; Allison, Simon J.; Sadiq, Maria; Basheer, Haneen A.; Ribeiro Morais, Goreti; Loadman, Paul M.; Pors, Klaus; Falconer, Robert A. |
| Journal | Scientific Reports |
| DOI | http://dx.doi.org/10.1038/srep33026 |
| Title | The use of thermographic imaging to evaluate therapeutic response in human tumour xenograft models (2016) |
| Authors | Hussain, Nosheen; Connah, David; Ugail, Hassan; Cooper, Patricia A.; Falconer, Robert A.; Patterson, Laurence H.; Shnyder, Steven D. |
| Journal | Scientific Reports |
| DOI | http://dx.doi.org/10.1038/srep31136 |
| Title | The Effect of Polysialic Acid Expression on Glioma Cell Nano-mechanics (2016) |
| Authors | Grant, Colin A.; Twigg, Peter C.; Saeed, Rida F.; Lawson, G.; Falconer, Robert A.; Shnyder, Steven D. |
| Journal | BioNanoScience |
| DOI | 10.1007/s12668-016-0192-2 |
| Title | An optimised assay for quantitative, high-throughput analysis of polysialyltransferase activity (2016) |
| Authors | Elkashef, Sara M.; Sutherland, Mark H.; Patterson, Laurence H.; Loadman, Paul M.; Falconer, Robert A. |
| Journal | ANALYST (PRINT) |
| DOI | http://dx.doi.org/10.1039/C6AN01073C |
| Title | Novel strategies for the synthesis of unsymmetrical glycosyl disulfides (2016) |
| Authors | Ribeiro Morais, Goreti; Springett, Bradley R.; Pauze, Martin; Schröder, Lisa; Northrop, Matthew; Falconer, Robert A. |
| Journal | Organic and Biomolecular Chemistry |
| DOI | https://doi.org/10.1039/C6OB00230G |
| Title | The Tumor-Targeted Prodrug ICT2588 Demonstrates Therapeutic Activity Against Solid Tumors and Reduced Potential For Cardiovascular Toxicity (2014) |
| Authors | Gill, Jason H.; Loadman, Paul M.; Shnyder, Steven D.; Cooper, Patricia A.; Atkinson, Jennifer M.; Ribeiro Morais, Goreti; Patterson, Laurence H.; Falconer, Robert A. |
| Journal | Molecular Pharmaceutics |
| DOI | 10.1021/mp400760b |
| Title | Development of Novel Tumor-Targeted Theranostic Nanoparticles Activated by Membrane-Type Matrix Metalloproteinases for Combined Cancer Magnetic Resonance Imaging and Therapy (2014) |
| Authors | Ansari, C.; Tikhomirov, G.A.; Hong, S.H.; Falconer, Robert A.; Loadman, Paul M.; Gill, Jason H.; Castaneda, R.; Hazard, F.K.; Tong, L.; Lenkov, O.D.; Felsher, D.W.; Rao, J.; Daldrup-Link, H.E. |
| Journal | Small |
| DOI | 10.1002/smll.201301456 |
| Title | Micro-community cytometry: Sensing changes in cell health and glycoconjugate expression by imaging and flow cytometry (2013) |
| Authors | Smith P.;Falconer R.;Errington R. |
| Journal | Journal of Microscopy |
| DOI | 10.1111/jmi.12060 |
| Title | Carbohydrate-based molecules for Molecular Imaging in Nuclear Medicine (2013) |
| Authors | Ribeiro Morais G.;Falconer R.;Santos I. |
| Journal | European Journal of Organic Chemistry |
| DOI | 10.1002/ejoc.201201457 |
| Title | NCAM polysialylation during adherence transitions: Live cell monitoring using an antibody-mimetic EGFP-endosialidase and the viability dye DRAQ7 (2013) |
| Authors | Smith P.;Furon E.;Wiltshire M.;Chappell S.;Patterson L.;Shnyder S.;Falconer R.;Errington R. |
| Journal | Cytometry Part A |
| DOI | 10.1002/cyto.a.22306 |
| Title | Pharmacological Inhibition of polysialyltransferase ST8SiaII Modulates Tumour Cell Migration (2013) |
| Authors | Al-Saraireh, Yousef M.J.; Sutherland, Mark H.; Springett, Bradley R.; Freiberger, F.; Ribeiro Morais, Goreti; Loadman, Paul M.; Errington, R.J.; Smith, P.J.; Fukuda, M.; Gerardy-Schahn, R.; Patterson, Laurence H.; Shnyder, Steven D.; Falconer, Robert A. |
| Journal | PLoS ONE |
| DOI | 10.1371/journal.pone.0073366 |
| Title | Polysialyltransferase: A new target in metastatic cancer (2012) |
| Authors | Falconer R.;Errington R.;Shnyder S.;Smith P.;Patterson L. |
| Journal | Current Cancer Drug Targets |
| DOI | 10.2174/156800912803251225 |
| Title | Synthesis and biological evaluation of colchicine C-ring analogues tethered with aliphatic linkers suitable for prodrug derivatisation (2012) |
| Authors | Fournier-Dit-Chabert J.;Vinader V.;Santos A.;Redondo-Horcajo M.;Dreneau A.;Basak R.;Cosentino L.;Marston G.;Abdel-Rahman H.;Loadman P.;Shnyder S.;Díaz J.;Barasoain I.;Falconer R.;Pors K. |
| Journal | Bioorganic and Medicinal Chemistry Letters |
| DOI | 10.1016/j.bmcl.2012.09.104 |
| Title | An optimized method for the synthesis of amino-functionalized phosphatidylcholine (2012) |
| Authors | Kong F.;Morais G.;Falconer R.;Sutton C. |
| Journal | Tetrahedron Letters |
| DOI | 10.1016/j.tetlet.2011.11.100 |
| Title | Identification of an acetyl disulfide derivative in the synthesis of thiosialosides (2010) |
| Authors | Morais G.;Oliveira I.;Humphrey A.;Falconer R. |
| Journal | Carbohydrate Research |
| DOI | 10.1016/j.carres.2009.10.017 |
| Title | Development of a novel tumor-targeted vascular disrupting agent activated by membrane-type matrix metalloproteinases (2010) |
| Authors | Atkinson J.;Falconer R.;Edwards D.;Pennington C.;Siller C.;Shnyder S.;Bibby M.;Patterson L.;Loadman P.;Gill J. |
| Journal | Cancer Research |
| DOI | 10.1158/0008-5472.CAN-10-1440 |