Professor Robert Falconer
Professor of 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
Robert Falconer is a Pharmacist, having obtained his pharmacy degree from The School of Pharmacy, University of London (now UCL School of Pharmacy). He undertook his pre-registration pharmacy training year at Joyce Green Hospital, Dartford, Kent. He then returned to academia in London, where he undertook a PhD in medicinal chemistry (2000). He was subsequently appointed Research & Teaching Fellow, and then Lecturer in Pharmaceutical Sciences.
A move to the new Institute of Cancer Therapeutics (ICT), University of Bradford followed (2005), to establish one of three new medicinal chemistry teams there. 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. His major interests include the cancer cell glycocalyx, and in the development of protease-activated anticancer prodrugs.
He has served as Deputy Director of the ICT since Feb 2017, overseeing medicinal chemistry and drug discovery, and was promoted to Professor of Medicinal Chemistry in 2019. He is a founder of University spin-out company Incanthera plc, leads the ICT's £2m Doctoral Training Centre, and currently co-leads a £1.5m programme grant from Yorkshire Cancer Research. 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, 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).
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, 12, 925-939). We are employing computational methods to aid the inhibitor design process and have the capability to assess enzyme inhibition (see 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.
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, 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.
Current Team members
PhD students: Marrwa Ali; Katreen Banisalman; Athina Polykandritou (ICT DTC); Hannah Spencer (BCRT); Alexandra Serre (ICT DTC)
Research Assistants: Ms Zubeda Khatoon
Post-Doctoral Researchers: Dr Francis Mprah Barnieh (YCR); Dr Goreti Ribeiro Morais (ICT DTC); Dr David Pajtas (BCNow)Interns: Mr Laurie Hughes (University of York)
| Date | Role | Title / Description | Funder | Award |
|---|---|---|---|---|
| 01-OCT-14 - 30-SEP-21 | Co-PI | Yorkshire Cancer Research - Cancer Medicines Discovery II | 1546536 | |
| 01-OCT-18 - 30-SEP-22 | PI | Bone Cancer Research Trust - Development of a targeted methotrexate prodrug with enhanced therapeutic index for osteosarcoma | 116626 | |
| 01-OCT-18 - 30-SEP-28 | PI | Incanthera plc - ICT Doctoral Training Centre | 2000000 | |
| 01-JAN-19 - 30-NOV-21 | PI | Breast Cancer Now - Development of a novel, targeted cytotoxic treatment for breast cancer | 191037 | |
| 01-OCT-19 - 30-SEP-23 | Co-I | Kidscan - Investigation of CYP2W1 as a therapeutic target in childhood rhabdomyosarcoma | 63675 |
| Contract Researchers | |
|---|---|
| Name | Dr Francis M Barnieh |
| Role | Postdoctoral Researcher |
| Project | Yorkshire Cancer Research |
| Name | Dr Goreti Morais |
| Role | Postdoctoral Researcher |
| Project | ICT Doctoral Training Centre |
| Name | Dr David Pajtas |
| Role | Postdoctoral Researcher |
| Project | Breast Cancer Now |
Teaching
Teaching interests
Robert's teaching activities are primarily focused on the application of medicinal chemistry to cancer drug discovery, with contributions to several modules across the ICT's MSc and MRes post-graduate courses in Cancer Drug Discovery, Cancer Pharmacology, and Drug Toxicology and Safety Pharmacology. He leads the Principles of Drug Discovery module (INC7014-B), which provides an overview of the various elements of the drug discovery process, from designing molecules, through in vitro screening, drug metabolism and ultimately clinical trials. He contributes to some modules in the MPharm Pharmacy and BSc Clinical Sciences degrees.
He regularly supervises research projects and dissertations for MSc/MRes and undergraduate students, including ERASMUS placement students from overseas partners, and is also a personal academic tutor for students undertaking the Foundation in Clinical Sciences course.
Professional activities
- 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
- 16-DEC-19: University of Bradford - Professor of Medicinal Chemistry
- 01-SEP-13: University of Bradford - Reader in Medicinal Chemistry
- 01-SEP-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
- Royal Society of Chemistry, Fellow
- British Association for Cancer Research, Member
- European Association for Cancer Research, Member
- Amercian Association for Cancer Research, Member
- Royal Pharmaceutical Society / General Pharmaceutical Council, Member
- 01-JAN-17: - Vice-Chancellor's Award for Excellence
- 01-JAN-19: - Fellow, Royal Society of Chemistry
- Deputy Director, ICT
- Research Group Leadership: School of Pharmacy and Medical Sciences Team Leadership Group Member
- Programme & Module Management: Teaching Module Leadership: INC6001-B (Fundamentals of Drug Discovery)
- Programme & Module Management: Teaching Module Leadership: INC7014-B (Fundamentals of Drug Discovery)
- External Examiner: MPharm Pharmacy, BSc Pharmaceutical Sciences, BSc Pharmaceutical Biotechnology School of Pharmacy, Queen’s University Belfast (2020-24)
- Scientific Advisory Board Member: Health Research Charities Ireland/ Health Research Board Ireland Joint Funding Scheme (2020)
- External Examiner: MRes Drug Sciences, UCL School of Pharmacy Joint Postgraduate Board (2018-22)
- Scientific Advisory Board Member: Medical Research Charity Group/ Health Research Board Ireland Joint Funding Committee (2018)
- Scientific Committee Member: Kidscan Children’s Cancer Research (2016-19)
- Scientific Advisory Board Member: Neuroblastoma UK (2016)
- Editorial Board Member: Scientific Reports (Nature publishing group) (2016-)
- Co-Founder, Member of Scientific Advisory Board: Incanthera plc (www.incanthera.com)
- Committee Member: RSC Central Yorkshire Local Section Member Network (2008-10; 2012-18)
- Honorary Treasurer: RSC Central Yorkshire Local Section Member Network (2012-18; 3 terms)
- Elected Member: EPSRC Peer Review College (2006-)
Publications
| Peer Reviewed Journal | |
|---|---|
| Title | Glycosyl disulfides: importance, synthesis and application to chemical and biological systems (2021) |
| Authors | Ribeiro Morais, G.; Falconer, R.A. |
| Journal | Organic and Biomolecular Chemistry |
| DOI | 10.1039/D0OB02079F |
| Title | Progress towards a clinically-successful ATR inhibitor for cancer therapy (2021) |
| Authors | Barnieh, F.M.; Loadman, P.M.; Falconer, R.A. |
| Journal | Current Research in Pharmacology and Drug Discovery |
| DOI | 10.1016/j.crphar.2021.100017 |
| Title | An assay for quantitative analysis of polysialic acid expression in cancer cells (2021) |
| Authors | Guo, X.; Elkashef, S.M.; Patel, A.; Ribeiro Morais, G.; Shnyder S.D.; Loadman, P.M.; Patterson, L.H.; Falconer, R.A. |
| Journal | Carbohydrate Polymers |
| DOI | 10.1016/j.carbpol.2021.117741 |
| Title | An efficient assay for identification and quantitative evaluation of potential polysialyltransferase inhibitors. (2020) |
| Authors | Guo X; Malcolm J.R.; Ali M.M.; Ribeiro Morais G; Shnyder S.D.; Loadman P.M.; Patterson L.H.; Falconer R.A. |
| Journal | ANALYST (PRINT) |
| DOI | 10.1039/d0an00721h |
| Title | Novel Ran-RCC1 inhibitory peptide-loaded nanoparticles have anti-cancer efficacy in vitro and in vivo (2019) |
| Authors | Haggag, Y.A.; Matchett, K.B.; Falconer, R.A.; Isreb, M.; Jones, J.; Faheem, A.; McCarron, P.; El-Tanani, Mohamed |
| Journal | Cancers |
| DOI | 10.3390/cancers11020222 |
| Title | Recent advances in the analysis of polysialic acid from complex biological systems (2019) |
| Authors | Guo, X.; Elkashelf, S.M.; Loadman, P.M.; Patterson, L.H.; Falconer, R.A. |
| Journal | Carbohydrate Polymers |
| DOI | 10.1016/j.carbpol.2019.115145 |
| Title | Theranostic nanoparticles enhance the response of glioblastomas to radiation (2019) |
| Authors | Wu, W.; Klockow, J.L.; Mohanty, S.; Ku, K.S.; Aghighi, M.; Melemenidis, S.; Chen, Z.; Li, K.; Ribeiro Morais, Goreti; Zhao, N.; Schlegel, J.; Graves, E.E.; Rao, J.; Loadman, Paul M.; Falconer, R.A.; Mukherjee, S.; Chin, F.T.; Daldrup-Link, H.E. |
| Journal | Nanotheranostics |
| DOI | 10.7150/ntno.35342 |
| Title | Membrane-type matrix metalloproteinases: 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 | 10.20517/2394-4722.2017.40 |
| Title | Rationalized Computer-Aided Design of Matrix-Metalloprotease-Selective Prodrugs (2017) |
| Authors | Jain, M.; Harburn, J.J.; Gill, J.H.; Loadman, P.M.; Falconer, R.A.; Mooney, C.A.; Cobb, S.L.; Berry, David J. |
| Journal | Journal of Medicinal Chemistry |
| DOI | 10.1021/acs.jmedchem.6b01472 |
| 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.; Pasani, 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 | 10.1158/1535-7163.MCT-17-0022 |
| 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, R.A.; Gerardy-Schahn, R. |
| Journal | ChemBioChem |
| DOI | 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 | 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 | 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 | 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 | 10.1039/c6ob00230g |
| Title | 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 Cancer Therapeutics |
| 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 | 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 | 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 | 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 | 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 | 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 |