Institute of Cancer Therapeutics

El-Khamisy is pharmacist interested in understanding how cells maintain genomic integrity and its impact on health. His lab uses interdisciplinary approach fusing genetics, chemistry and biology with clinical expertise. El-Khamisy early work demonstrated a role for PARP1 and CK2 during chromosomal single-strand break (SSB) repair (NAR 2003, Cell 2004). He then moved into more clinical aspects, which led to the identification, for the first time, of a defect in SSB repair in two human disorders (Nature 2005 and 2006). Following training at St Jude Hospital in the US, he employed mice to demonstrate the importance of SSB repair for organismal function (EMBO J 2007 and Nature Neuroscience 2009). His interest in this area led to a search for novel activities that repair protein-linked DNA breaks (PDBs) and resulted in the discovery of the enzyme that repairs topoisomerase 2 - mediated DNA damage, TDP2 (Nature 2009).This seminal finding is critical for a broad range of human disease including cancer. El-Khamisy demonstrated that PDBs are pathogenic in other human disorders (Hum Mol Gent 2010, Nature Genetics 2014, Nature Neuroscience 2017) and identified key post-translational modifications and functions (Nature Communications 2012, NAR 2012 & 2016, Cell Reports 2018 and Nature communications 2020). His lab made observations that contributed to the discovery of links between XRCC1/PARP1 and human disease (Nature 2017). he reviewed the importance of PDB repair during transcription (Nature Rev Cancer 2015, Brain 2018) and described how it maintains mitochondrial gene transcription (Science Advances 2017). Together with colleagues in Sheffield they uncovered a novel mechanism by which typhoid toxin exhausts the DNA repair machinery (Nature Communications 2019) and in collaboration with colleagues in Oxford, they discovered novel players in the DNA damage response with implications in cancer (Nature communications 2020). He initiated translational research programmes leading to drug discovery awards from AstraZeneca and CRUK. Fusing his expertise with clinicians and nanotechnology led to development of new technologies and influenced healthcare policies (Biosensors 2017 and Ebiomedicine 2018).

His work in genomic medicine has been cited ~8000 times with an H-index of 33, and is recognized nationally by winning a Wellcome trust fellowship, a Lister Institute of Preventative Medicine fellowship and he is currently the holder of the highly prestigious Wellcome Trust Investigator Award. His work was recognized internationally by the Nobel Laurette Dr Zewail, by winning the Shoman Prize for Medical Sciences and the state award for excellence in science.

Selected publications:

1. Fielden J, Wiseman K, …….Maughan TS, El-Khamisy SF, Ramadan K (2020). TEX264 coordinates p97- and SPRTN-mediated resolution of topoisomerase 1-DNA adducts. Nature communications, 9;11(1):1274. [Discovery of TEX264 as a topoisomerase-mediated DNA break repair factor].
2. Kim HR, Santhakumar K, Markham E, Baldera D, Greenald D, Bryant HE, El-Khamisy SF, van Eeden FJ (2020). Nucleosides Rescue Replication-Mediated Genome Instability of Human Pluripotent Stem Cells. Stem Cell Reports, 9;14(6):1009-1017
3. Ibler A, Bulgakova N, El-Khamisy SF, Humphreys D (2019). A novel DNA damage response to replicative stress by the typhoid toxin facilitates cellular senescence and Salmonella infection. Nature communications, 10: 4040 [Typhoid toxin hijacks DNA repair machines and accelerates ageing].
4. Liao C, …..., Dickman MJ, El-Khamisy SF (2018). UCHL3 regulates topoisomerase induced chromosomal break repair by controlling TDP1 proteostasis. Cell Reports, 23, 3352–3365 [Discovery of a mechanism regulating protein homeostasis during PDB repair].
5. Walker C, Herranz-Martin S, ………A, ShawPJ, Hautbergue GM, Azzouz M, El-Khamisy SF. (2017). C9orf72 Expansion Disrupts ATM-mediated Chromosomal Break Repair. Nature Neuroscience, 45: 1159 [Discovery of a mechanism underpinning genome instability caused by C9orf72 expansion]
6. Chiang S-C, Meagher M., Kassouf N., Hafezparast M., McKinnon P.J., Haywood R., El-Khamisy SF. (2017). Mitochondrial protein-linked DNA breaks perturb mitochondrial gene transcription and trigger free radical induced DNA damage. Science Advances. 3(4):e1602506. [The identification of a mitochondrial topoisomerase repair pathway]
7. Hautbergue GM , …., Isaacs AM, El-Khamisy, SF, De Vos KJ, Ning K, Azzouz M, Whitworth AJ, Shaw, PJ (2017). SRSF1-dependent nuclear export inhibition of C9ORF72 repeat transcripts prevents neurodegeneration. Nature Communications, 8:16063.
8. Meisenberg C, Ashour ME, …. Downs JA, Ward SE, El-Khamisy SF. (2017). Epigenetic changes in histone acetylation underpin resistance to the topoisomerase I inhibitor irinotecan. Nucleic Acids Res. 45(3):1159-117
9. Ashour ME, Atteya R, El-Khamisy SF. (2015). Topoisomerase-mediated chromosomal break repair: an emerging player in many games. Nature Rev Cancer. 15(3):137-51
10. Meisenberg C, ….., El-Khamisy SF (2015). Clinical roles for TDP1 and TOP1 in modulating colorectal cancer response to irinotecan. Mol Cancer Ther. 14(2): 575-85
11. Gómez-Herreros F, Schuurs-Hoeijmakers JH, …. de Brouwer AP, Cavalleri GL, El-Khamisy SF*, de Vries BB*, Caldecott KW* (2014). TDP2 protects transcription from abortive topoisomerase activity. Nat Genet. 46: 516–52 *Corresponding author
12. Hudson, J.R., Chiang, S., Wells, O.S., Rookyard, C., El-Khamisy, SF (2012). SUMO modification of the neuroprotective protein TDP1 facilitates chromosomal single-strand break repair. Nature Communications, 13; 3:733
13. Cortes-Ledesma F.*, El-Khamisy, SF *, Zuma, M., Osbourne, K., Caldecott, K.W. (2009). Identification of a Human 5’-Tyrosyl DNA Phosphodiesterase That Repairs Topoisomerase- Mediated DNA Damage. Nature, 461(7264):674-8 * Equal contributions. [Discovery of the TOP repair factor TDP2]
14. Ahe,l I., Rass, U., El-Khamisy, SF, ….. West, S.C (2006). Aprataxin resolves abortive DNA ligation intermediates. Nature, 443, 713-6.
15. El-Khamisy, SF, …. and Caldecott, K.W. (2005) Defective DNA Single-Strand Break Repair in Spinocerebellar Ataxia with Axonal Neuropathy-1. Nature, 434, 108-113. [Discovery of DNA single-strand break repair defect in a human disease]
16. El-Khamisy, SF, …. and Caldecott, K.W. (2003) A requirement for PARP-1 for the assembly of XRCC1 nuclear foci at sites of oxidative DNA damage. Nucleic Acids Res, 31, 5526-5533.

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Dr Chris Twelves is Professor of Clinical Cancer Pharmacology and Oncology and Director of the NIHR Leeds Clinical Research Facility.

He is a medical oncologist with a particular interest in new drug development and clinical pharmacology; his clinical practice has been in colorectal and breast cancer.

After training as an oncologist in London he was Senior Lecturer, then Reader, in Medical Oncology in Glasgow at the Beatson Oncology Centre before taking up his current post at the University of Leeds and St James’s Institute of Oncology.

Prof Twelves has been a member of the Cancer Research UK New Agents Committee, Chair of the New Drug Development Group of the EORTC and was Scientific Chair of the Berlin 2009 ECCO-ESMO 34 meeting.  He has been involved in the development of several important new agents including capecitabine, and eribulin.  Professor Twelves has a particular interest in early clinical trials and pharmacokinetics including intra-tumoural drug pharmacokinetics.

Professor Twelves has published over 200 papers in journals including the New England Journal of Medicine, Lancet and Journal of Clinical Oncology and spoken at numerous international meetings.  He has also edited, or contributed to, several books including one on Phase I clinical trials and another on the design of Phase II clinical trials.

Professor Paul Loadman heads the drug metabolism team at the Institute of Cancer Therapeutics, University of Bradford and has >20years experience studying the pharmacokinetics and metabolism of anti-cancer drugs. The team in Bradford have studied a wide range of clinically available and novel small molecules including antimetabolites, platinating and alkylating agents, peptides and antivascular compounds. Prof Loadman is actively involved in the design, analysis and reporting of pre-clinical and clinical pharmacokinetic studies and acts as a pharmacokinetic and drug metabolism consultant for numerous pharmaceutical and biotechnology companies.

Together with Prof Twelves (Clinical Director,) the DMPK team have established a Quality Management System within the ICT which has enabled a strong involvement in the pharmacokinetic monitoring of small molecules in major clinical trials. Other major clinical collaborations include with Professor Mark Hull at the University of Leeds (The seAFOod Polyp Prevention Trial, www.seafood-trial.co.uk) where the laboratory in Bradford are analyzing a series of bioactive lipid mediators such as ω-3 PUFAs, resolvin E1 and PGE-M in plasma, urine, erythrocytes and rectal mucosa in order to gain insights into the mechanism of action of EPA and aspirin.

1. Jason H. Gill, Paul M. Loadman, Steven D. Shnyder, Patricia Cooper, Laurence H.Patterson, Jennifer M. Atkinson, Goretti Ribeiro Morais, Robert A. Falconer The Tumor-Targeted Vascular Disrupting Agent ICT2588 Demonstrates Therapeutic Activity Against Solid Tumours and Reduced Potential For Cardiovascular Toxicity.. (2014) Pharmaceutics, 11, 1294−1300

2. Probing cytochrome P450-mediated activation with a truncated azinomycin analogue, Victoria Vinader, Maria Sadiq, Mark Sutherland, Mengying Huang, Paul M. Loadman, Lina Elsalem, Steven D. Shnyder, Hongjuan Cui, Kamyar Afarinkia, Mark Searcey, Laurence H. Patterson and Klaus Pors, Med. Chem. Commun., 2015,6, 187-191      

3. Suchismita Mohanty, Zixin Chen, Kai Li, Goreti Ribeiro Morais, Jessica Klockow, Ketan Yerneni, Laura Pisani, Frederick T Chin, Siddharta Mitra, Samuel jCheshier, Edwin Chang, Sanjiv Sam Gambhir, Jianghong Rao, Paul M. Loadman, Robert A. Falconer, Heike E Daldrup-Link,(2017), A novel theranostic strategy for MMP-14 expressing glioblastomas impacts survival- Mol Cancer Ther. 2017 Sep;16(9):1909-1921           

4. E.Hubbard, M.Jove, P.M.Loadman, R.M.Phillips, C.J.Twelves S.W.Smye, Drug delivery in a tumour cord model: a computational simulation, (2017).R. Soc. Open Sci. 4: 170014

5. A randomised trial of the effect of omega-3 polyunsaturated fatty acid supplements on the human intestinal microbiota , Henry Watson, Suparna Mitra, Fiona C Croden, Morag Taylor, Henry M Wood, Sarah L Perry, Jade A Spencer, Phil Quirke, Giles J Toogood, Clare L Lawton, Louise  Dye, Paul M Loadman, Mark A Hull, Gut, (2018);67:1974–1983. doi:10.1136/gutjnl-2017-314968

6. Eicosapentaenoic acid (EPA) and/or aspirin for prevention of colorectal adenomas (The seAFOod Polyp Prevention Trial): a multicentre, double-blind, placebo-controlled, randomised 2x2 factorial phase 3 trial. Mark A Hull, K. Sprange, Trish Hepburn, Wei Tan, Aisha Shafyat, Colin J Rees, G. Clifford, Richard FA Logan, Paul M Loadman, E. Williams, Diane Whitham, Alan A Montgomery, on behalf of the seAFOod Collaborative Group (2018), The Lancet, Vol 392 p2583-94

7. Cellular uptake and efflux of palbociclib in vitro in single cell and spheroid models, M. Jove, J. A. Spencer, M. E. Hubbard, E. C. Holden, R. D. O’Dea, B. S. Brook, R. M. Phillips, S. W. Smye, P. M. Loadman, C. J. Twelves (2019) J of Exp. Ther.Jun 12. doi: 10.1124/jpet.119.25669

8. Precision pharmacology: Mass spectrometry imaging and pharmacokinetic drug resistance Maria Jove, Jade Spencer, M. Clench,Paul M Loadman and Chris Twelves(2019), Vol 141, 153-162 Critical Reviews in Oncology/Hematology org/10.1016/j.critrevonc.2019.06.008           

9. Wu W, Klockow JL, Mohanty S, Ku KS, Aghighi M, Melemenidis S, Chen Z, Li K, Morais  GR, Zhao N, Schlegel J, Graves EE, Rao J, Loadman PM, Falconer RA, Mukherjee S, Chin FT, Daldrup-Link HE. Theranostic nanoparticles enhance the response of glioblastomas to radiation. Nanotheranostics 2019; 3(4):299-310. doi:7150/ntno.35342

10.  Recent advances in the analysis of polysialic acid from complex biological systems Xiaoxiao Guo, Sara M. Elkashef, Mark Sutherland, Paul M. Loadman and Robert A. Falconer (2019) Carbohydrate Polymers August 2019 DOI: 10.1016/j.carbpol.2019.115145                        

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Robert is a registered pharmacist and medicinal chemist primarily focused on anticancer drug development. He has interests in 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 (Curr Cancer Drug Targets 2012), and notably neuroblastoma. Computational methods aid the inhibitor design process, and in-house expertise enables assessment of enzyme inhibition (Analyst 2020), cell-surface polySia decoration (Carbohydr Polymers 2019), and effects on cell-cell and cell-matrix adhesion, cell migration and invasion (PLoS ONE 2013, Scientific Rep 2016 and ChemBioChem 2017). This work is currently supported by Yorkshire Cancer Research (programme grant), and the ICT Doctoral Training Centre (ICT DTC), and has previously been supported by EPSRC and Wellcome Trust. The Falconer group is also focused on the transformation of potent cytotoxic agents to inactive peptide-conjugates that are selectively activated within the tumour microenvironment by tumour specific enzymes, particularly matrix metalloproteinases. Solution and solid phase chemistry is employed 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. He is co-inventor of four patents associated with this technology. Lead prodrug ICT2588 (Cancer Res 2010, Mol Pharm 2014) is currently progressing towards a Phase I clinical trial with Ellipses Pharma, having been licenced by Incanthera plc. A collaboration with the Daldrup-Link group (Standford University, USA) has led to development of a novel theranostic prodrug ICT-CLIO, which has shown efficacy in breast cancer (Small 2014), and glioblastoma (Mol Cancer Ther  2017) and synergy with readiotherapy (Nanotheranostics 2019). Current projects are focused on development of novel treatments for breast cancer (Breast Cancer Now), prostate cancer (ICT DTC) and osteosarcoma (Bone Cancer Research Trust).

He is a founder of University spin-out company Incanthera plc, currently leads the ICT's £2m Doctoral Training Centre, and 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).

Selected publications:

1. Guo, X.; Malcolm, J.R.; Ali, M.M.; Ribeiro Morais, G.; Shnyder, S.D.; Patterson, L.H.; Loadman, P.M.; Falconer, R.A. “An efficient assay for identification and quantitative evaluation of potential polysialyltransferase inhibitors.” Analyst, 2020, 145. 4512-4521.
2. 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. “Radiation plus theranostic combination therapy for targeting glioblastomas.” Nanotheranostics, 2019, 3, 299-310.
3. Guo, X.; Elkashef, S.M; Loadman, P.M.; Patterson, L.H.; Falconer, R.A. “Recent advances in analysis of polysialic acid from complex biological systems.” Carbohydrate Polymers, 2019, 224, 11545.
4. 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. “A novel theranostic strategy for MMP-14 expressing glioblastomas impacts survival.” Molecular Cancer Therapeutics, 2017, 16, 1909-1921.
5. Ehrit, J.; Keys, T.G.; Sutherland, M.; Wolf, S.; Meier, C.; Falconer, R.A.; Gerardy-Schahn, R. “Exploring and Exploiting Acceptor Preferences of the Human Polysialyltransferases as a Basis for an Inhibitor Screen.” ChemBioChem, 2017, 18, 1332-1337.
6. Elkashef, S.M.; Allison, S.J.; Sadiq, M.; Basheer, H.A.; Ribeiro Morais, G.; Loadman, P.M.; Pors, K.; Falconer, R.A. “Polysialic acid sustains cancer cell survival and migratory capacity in a hypoxic environment.” Scientific Reports, 2016, 6, 33026.
7. Gill, J.H.; Loadman, P.M.; Shnyder, S.D.; Cooper, P.A.; Atkinson, J.M.; Ribeiro Morais, G.; Patterson, L.H.; Falconer, R.A. “The Tumor-Targeted Prodrug ICT2588 Demonstrates Therapeutic Activity Against Solid Tumors and Reduced Potential For Cardiovascular Toxicity.” Molecular Pharmaceutics, 2014, 11, 1294−1300.
8. Ansari, C.; Tikhomirov, G.A.; Hong, S.H.; Falconer, R.A.; Loadman, P.M.; Gill, J.H.; Castaneda, R.; Hazard, F.K.; Tong, L.; Felsher, D.W.; Rao, J.; Daldrup-Link, H.E. “Development of Novel Tumor-Targeted Theranostic Nanoparticles Activated by Membrane-Type Matrix Metalloproteinases for Combined Cancer Magnetic Resonance Imaging and Therapy.” Small, 2014, 10, 566-575 (front cover p 474).
9. Al-Saraireh, Y.M.J.; Sutherland, M.; Springett, B.R.; Freiberger, F.; Ribeiro Morais, G.; Loadman, P.M.; Errington, R.J.; Smith, P.J.; Fukuda, M.; Gerardy-Schahn, R.; Patterson, L.H.; Shnyder, S.D.; Falconer, R.A. “Pharmacological inhibition of polysialyltransferase ST8SiaII modulates tumour cell migration.” PLoS ONE, 2013, 8, e73366.
10. Atkinson, J.M.; Falconer, R.A.; Edwards, D.R.; Pennington, C.J.; Siller, C.S.; Shnyder, S.D.; Bibby. M.C.; Patterson, L.H.; Loadman, P.M.; Gill, J.H. “Development of a tumor-targeted vascular disrupting agent activated by Membrane-type Matrix Metalloproteinases (MT-MMPs).” Cancer Research, 2010, 70, 6902-6912.

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Klaus Pors graduated with a BEng from the University of Southern Denmark (1998) and a PhD from UCL School of Pharmacy (2002). His PhD was focused on the discovery of novel agents to circumvent drug-resistance mechanisms and hypoxia-activated prodrugs (HAPs). Dr Pors is driven by opportunities to translate research hypotheses into commercial and/or clinical products. His research interests lie at the interface of chemistry and biology and broadly include four strategies focused on the development of (i) chemical and biological tools designed to aid the understanding of the mechanism of action and molecular target engagement of new chemotypes (ii) targeted chemotherapy including prodrugs and new types of antibody-directed conjugates (ADCs), (iii) molecular fluorescent probes to paint fixed/live cells and (iv) molecular delivery devices that are designed to enable drugs to overcome problems with drug metabolism and pharmacokinetics (DMPK).

Current research efforts include work on tumour-selective therapeutic strategies using bio-reductive (HAPs) or bio-oxidative (duocarmycins bioprecursors) modes of activation have led to proof of concept technology acquired by biotech companies. Current research is funded by Yorkshire Cancer Research (programme grant), Breast Cancer Now, Kidscan and the ICT Doctoral Training Centre (ICT DTC). Dr Pors is also working on solutions on how to identify and treat aggressive tumour-initiating cells with stem cell properties and include probing aldehyde dehydrogenase activity for therapeutic intervention. This work has enjoyed funding from EPSRC (Case Award), Prostate Cancer UK, Royal Society, and is currently funded by the UoB International Development Fund scheme. Parallel activities include a major interest in fluorophore discovery, research which has contributed to the development of several fluorescent reagents including DRAQ9 (commercially available at www.biostatus.com).

Dr Pors is passionate about bringing chemistry to the forefront of cancer research and other life sciences, and as ICT coordinator of GCSE and A-level placements is a strong proponent of inspiring the next generation of scientists. He has in the past served as Editor and Chair of AACR’s Chemistry in Cancer Research editorial board (CICR, 2012-2016), committee member of the British Association for Cancer Research (BACR, 2008-11) and currently serves as a member of the RSC’s Chemical Biology & Bioorganic Chemistry committee.

Publications

1.      Pippione AC, Carnovale IM, Bonanni D, Marini E, Sini M, Pors K, Adinolfi S, Zonari D, Fustuccia C, Goyal P, Friemann R, Bagnati R, Boschi D, Oliaro-Bosso S, Lolli ML. Potent and selective Aldo-Keto Reductase 1C3 (AKR1C3) Inhibitors based on the benzoisoxazole moiety: application of a Bioisosteric Scaffold Hopping Approach to Flufenamic acid. Eur J Med Chem. 2018 Apr 25;150:930-945. doi: 10.1016/j.ejmech.2018.03.040. Epub 2018 Mar 16.

2.      Sneha, S, Nagare, R.P., Krishnapriya, S., Pors, K. and Ganesan, T.S. Functional antibodies against cancer stem cells: A promising approach. Cancer Immunol Immunother. 2017 Nov;66(11):1383-1398. doi: 10.1007/s00262-017-2049-0. Epub 2017 Aug 24. Review. PubMed PMID: 28840297.

3.      Wright EP, Day HA, Ibrahim AM, Kumar J, Boswell LJ, Huguin C, Stevenson CE, Pors K*, Waller ZA*. Mitoxantrone and Analogues Bind and Stabilize i-Motif Forming DNA Sequences. Sci Rep. 2016 Dec 22;6:39456. doi: 10.1038/srep39456. PubMed PMID: 28004744. *Joint corresponding authors

4.      Vinader V, Sadiq M, Sutherland M, Huang M, Loadman PM, Elsalem L, Shnyder SD, Cui H, Afarinkia K, Searcey M, Patterson LH and Pors K. Probing cytochrome P450-mediated activation with a truncated azinomycin analogue. MedChemComm, 2015, 6, 187 - 191. doi: 10.1039/c4md00411f.

5.      Pors K* and Moreb J*. Aldehyde dehydrogenases in cancer: an opportunity for biomarker and drug development? Drug Discovery Today. 2014 Dec;19(12):1953-63. *Joint corresponding authors

6.      Thomas A, Perry T, Berhane S, Oldreive C, Zlatanou A, Williams LR, Weston VJ,  Stankovic T, Kearns P, Pors K*,Grand RJ*, Stewart GS*. The dual-acting chemotherapeutic agent Alchemix induces cell death independently of ATM and p53. Oncogene. 2015 Jun;34(25):3336-48. doi: 10.1038/onc.2014.266. Epub 2014 Aug 18 *Joint corresponding authors

7.      Sheldrake HM, Travica S, Johansson I, Loadman PM, Sutherland M, Elsalem L, Illingworth N, Cresswell AJ, Reuillon T, Shnyder SD, Mkrtchian S, Searcey M, Ingelman-Sundberg M, Patterson LH, Pors K. Re-engineering of the duocarmycin structural architecture enables bioprecursor development targeting CYP1A1 and CYP2W1 for biological activity. J Med Chem. 2013 Aug 8;56(15):6273-7. doi: 10.1021/jm4000209. Epub 2013 Jul 26.

8.      Travica S*, Pors K*, Loadman PM, Shnyder SD, Johansson I, Alandas MN, Sheldrake HM, Mkrtchian S, Patterson LH, Ingelman-Sundberg M. Colon cancer-specific cytochrome P450 2W1 converts duocarmycin analogues into potent tumor cytotoxins.  Clin Cancer Res. 2013 Jun 1;19(11):2952-61. doi: 10.1158/1078-0432.CCR-13-0238. Epub 2013 Apr 15. *Joint first authors

9.      Cosentino L, Redondo-Horcajo M, Zhao Y, Santos AR, Chowdury KF, Vinader V, Abdallah QM, Abdel-Rahman H, Fournier-Dit-Chabert J, Shnyder SD, Loadman PM, Fang WS, Díaz JF, Barasoain I, Burns PA, Pors K. Synthesis and biological evaluation of colchicine B-ring analogues tethered with halogenated benzyl moieties. J Med Chem. 2012 Dec 27;55(24):11062-6. doi:10.1021/jm301151t. Epub 2012 Dec

10.      Pors K, Loadman PM, Shnyder SD, Sutherland M, Sheldrake HM, Guino M, Kiakos K, Hartley JA, Searcey M, Patterson LH. Modification of the duocarmycin pharmacophore enables CYP1A1 targeting for biological activity. Chem Commun (Camb). 2011 Nov 28;47(44):12062-4. doi: 10.1039/c1cc15638a. Epub 2011 Oct 14.

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Richard Wheelhouse is a graduate (BSc and PhD) of the University of Leicester.  He held research positions in the Pharmacy schools at Aston, Nottingham (Professor Malcolm Stevens) and the University of Texas at Austin (Professor Laurence Hurley) before joining the Bradford School of Pharmacy in 1998.  

Expertise in the group encompasses compound design and synthesis, ligand–nucleic acid biophysics and in vitro evaluation. A major research interest is the chemistry of compounds of the temozolomide family – the imidazotetrazine prodrugs.  Particular expertise lies in applying a detailed understanding of the underlying chemistry of this fascinating class of compound to design novel molecules that overcome the constraints on the performance of temozolomide in the clinic. Other interests include targeting unusual nucleic acid structures such as three- and four-stranded DNA and DNA·RNA hybrid duplexes and probing drug-nucleic acid interactions using specialist techniques such as thermal scanning UV spectrophotometry, ITC and highfield NMR. Dr Wheelhouse teaches mostly on the MPharm course and coordinates student overseas exchange programmes for the School.

Selected Publications

1. Ruthenium-containing Linear Helicates and Mesocates with Tuneable p53 Selective Cytotoxicity in Colorectal Cancer Cells. S.J. Allison, D. Cooke, F.S. Davidson, P.I.P. Elliott, R.A. Faulkner, H.B.S. Griffiths, O.J. Harper, O. Hussain, P.J. Owen-Lynch, R.M. Phillips,* C.R. Rice,* S.L. Shepherd and R.T. Wheelhouse. Angew. Chem. Int. Ed. (2018) 130, 9947–9952. doi: 10.1002/anie.201805510
2. Preclinical Anti-cancer Activity and Multiple Mechanisms of Action of a Cationic Silver Complex Bearing N-heterocyclic Carbene Ligands. S.J. Allison, M. Sadiq, E. Baronou, P.A. Cooper, C. Dunnill, N.T. Georgopoulos, A. Latif, S. Shepherd, S.D. Shnyder, I.J. Stratford, R.T. Wheelhouse, C. Willans and R.M. Phillips. Cancer Letters (2017) 397, 98–107. dx.doi.org/10.1016/j.canlet.2017.04.041
3. Evaluation of Novel Imidazotetrazine Analogues Designed to Overcome Temozolomide Resistance and Glioblastoma Regrowth. Y.P. Ramirez, A.C. Mladek, R.M. Phillips, M. Gynther, J. Rautio, A.H. Ross,* R.T. Wheelhouse, J.N. Sakaria,* Mol. Cancer Ther. (2015) 14, 111–119. doi: 10.1158/1535-7163.MCT-14-0113. PubMed PMID: 25351918
4. Synthesis and Quantitative Structure–Activity Relationship of Imidazotetrazine Prodrugs with Activity Independent of O6-Methylguanine-DNA-methyltransferase, DNA Mismatch Repair and p53. D. Pletsas, E.A.E. Garelnabi, L. Li, R.M. Phillips, R.T. Wheelhouse.* J. Med. Chem. (2013) 56, 7120–7132. doi:10.1021/jm401121k. PubMed PMID: 23895620
5. Strategy for Imidazotetrazines with Anticancer Activity Independent of MGMT and MMR.  E.A.E. Garelnabi, D. Pletsas, L. Li, K. Kiakos, N. Karodia, J.A. Hartley, R.M. Phillips and R.T. Wheelhouse.* ACS Med. Chem. Lett. (2012) 3, 965–968. doi:10.1021/ml300132t. PubMed PMID: 24900418; PubMed Central PMCID: PMC4025673. 

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Dr Müller graduated in Biology and received his PhD in Biochemistry from the Ruhr-Universität Bochum in Germany. He then undertook postdoctoral research at Columbia University, New York and The National Cancer Institute (NIH) in Maryland, USA, where he investigated the mechanisms of transcriptional regulation and associated signal transduction pathways. Dr Müller continued pursuing these research themes as a group leader at the North West Cancer Research Institute in Bangor, North Wales and as a Senior Lecturer / Associate Professor at Warwick and Aston Medical Schools, before joining the University of Bradford in 2017.

Dr Müller’s current research focuses on the dynamic regulation of cellular signalling, specifically the MAPK pathways. MAPKs contribute to the aetiology of many cancers, are important for targeted therapies, and significantly impact on cancer drug resistance. The goal of Dr Müller’s research is to understand how the MAPK pathways maintain homeostasis under normal conditions, as well as the mechanisms that lead to a rewiring of the pathways in disease, in order to enable the development of improved targeted treatment options.

Selected publications:

1. Negative feedback regulation of the ERK1/2 MAPK pathway; Lake, D.; Corrêa, S.A.L.; Müller, J., Cellular and Molecular Life Sciences 73, 4397–441 (2016)
2. The Temporal Dynamics of Arc Expression Regulate Cognitive Flexibility; Wall, M.J.; Collins, D.R.; Chery, S.L.; Allen, Z.D.; Pastuzyn, E.D.; George, A.J.; Nikolova, V.D.; Moy, S.S.; Philpot, B.D.; Shepherd; J.D., Müller, J.; Ehlers, M.D.; Mabb, A.M.; Corrêa; S.A.L.; Neuron 98(6):1124-1132 (2018)
3. The scaffold protein KSR1, a novel therapeutic target for the treatment of Merlin-deficient tumors; Zhou, L.; Lyons-Rimmer, J.; Ammoun, S.; Müller, J.; Lasonder, E.; Sharma, V.; Ercolano, E.; Hilton, D.; Taiwo, I.; Barczyk, M.; Hanemann, C.O.; Oncogene 35(26), 3443-3453 (2016)

Dr Steve Shnyder, is a Senior Lecturer in Cancer Biology at the ICT. He has thirty years’ experience as a research scientist: 24 years post-doctoral, 18 months in a start-up pharma, with the past 18 years in a preclinical cancer pharmacology environment at Bradford. He has over 25 years’ experience of working with small mammals, mainly in the preclinical cancer pharmacology field. In his current position he is a Home Office Project and Personal Licence holder and is involved in the management and practical execution of Research and Knowledge Transfer in vivo and in vitro studies carried out at the ICT, working with both UK-based and international clients. His team has contributed to the screening packages of several novel anti-cancer compounds which have subsequently progressed to clinical trials and beyond, using both cell-based and in vivo technologies. He is an author on 65+ journal articles and numerous conference publications as well as three book chapters on in vivo methodology. In addition he has significant experience in the areas of histopathology, biochemistry and cell biology.

He line manages an Experimental Officer whose focus is in vivo studies, and a Research Technician whose focus is in vitro screening. He is a strong proponent of 3Rs philosophy, always striving to apply the 3Rs to all the work he does, and he has been a co-investigator on 2 project grants and a studentship specifically aimed at improving methodology in preclinical cancer pharmacology from a 3Rs standpoint.

Select publications

1. Soldevila-Barreda J, Azmanova M, Pitto-Barry A, Cooper P, Shnyder S, Barry N (2020). Preclinical anticancer activity of an electron-deficient organoruthenium (II) complex. ChemMedChem. 15:982-987. doi: 10.1002/cmdc.202000096.
2. O'Flaherty L, Shnyder SD, Cooper PA, Cross SJ, Wakefield JG, Pardo OE, Seckl MJ, Tavaré JM (2019). Tumor growth suppression using a combination of taxol-based therapy and GSK3 inhibition in non-small cell lung cancer. PLoS One. 14: e0214610. doi:10.1371/journal.pone.0214610.
3. Basheer HA, Pakanavicius E, Cooper PA, Shnyder SD, Martin L, Hunter KD, Vinader V, Afarinkia K (2018). Hypoxia modulates CCR7 expression in head and neck cancers. Oral Oncology 80: 64-73. doi.org/10.1016/j.oraloncology.2018.03.014
4. Allison SJ, Sadiq M, Baronou E, Cooper PA, Dunnill C, Georgopoulos NT, Latif A, Shepherd S, Shnyder SD, Stratford IJ, Wheelhouse R, Willans C, Phillips RM (2017). Preclinical anti-cancer activity and multiple mechanisms of action of a cationic silver complex bearing N-heterocyclic carbene ligands. Cancer Lett 403: 98-107. doi: 10.1016/j.canlet.2017.04.041.
5. Hussain N, Connah D, Ugail H, Cooper PA, Falconer RA, Patterson LH, Shnyder SD (2016). The use of thermographic imaging to evaluate therapeutic response in human tumour xenograft models. Scientific Reports 6:31136 DOI: 10.1038/srep31136.

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Helen Sheldrake studied Natural Sciences followed by a PhD in natural product synthesis at the University of Cambridge. After postdoctoral work at The University of Manchester, she joined the Institute of Cancer Therapeutics, University of Bradford as a RCUK Academic Fellow in Medicinal Chemistry. She is now a Lecturer in the School of Pharmacy and Medical Sciences, and School Health and Safety Lead.

Her research interests include:

- Synthesis and characterisation of new integrin targeting small molecules for the treatment of advanced cancers, particularly metastatic prostate cancer and malignant melanoma.

- Development of personalised anti-integrin agents: Identification of the optimum combination of integrins to target for effective treatment of a particular tumour.

- Investigation of combination therapies to combat integrin-mediated resistance to existing anticancer agents.

- Synthesis of biologically active natural products, and derivatives.

Publications

1. Exploration of [2 + 2 + 2] cyclotrimerisation methodology to prepare tetrahydroisoquinoline-based compounds with potential aldo–keto reductase 1C3 target affinity. A. R. N. Santos, H. M. Sheldrake, A. I. M. Ibrahim, C. C. Danta, D. Bonanni, M.Daga, S. Oliaro-Bosso, D. Boschi, M. L. Lolli and K. Pors. Med. Chem. Commun., 2019, 10, 1476-1480
2. RGD-Binding Integrins in Head and Neck Cancers, H. T. Ahmedah, L H. Patterson, S. D. Shnyder and H. M. Sheldrake. Cancers 2017, 9, 56; doi:10.3390/cancers9060056
3. Intramolecular thermal stepwise [2 + 2] cycloadditions: investigation of a stereoselective synthesis of [n.2.0]-bicyclolactones. A. Throup, L. H. Patterson, H. M. Sheldrake. Org Biomol Chem. 2016, 14, 9554-9559.
4. The solid phase synthesis of duocarmycin analogues and the effect of C-terminal substitution on biological activity. M. J. Stephenson, L. A. Howell, M. A. O'Connell, K. R. Fox, C. Adcock, J. Kingston, H. Sheldrake, K. Pors, S. P. Collingwood, M. Searcey. J Org Chem. 2015, 80, 9454-9467.
5. Strategies to inhibit tumor associated integrin receptors: rationale for dual and multi-antagonists. H. M. Sheldrake and L. H. Patterson. J. Med. Chem., 2014, 57, 6301-6315.
6. Re-engineering of the Duocarmycin Structural Architecture Enables Bioprecursor Development Targeting CYP1A1 and CYP2W1 for Biological Activity. H. M. Sheldrake, S. Travica, I. Johansson, P. Loadman, M. Sutherland, L. Elsalem, N. Illingworth, A. Cresswell, T. Reuillon, S. Shnyder, S. Mkrtchian, M. Searcey, M. Sundberg, L. Patterson, K. Pors. J. Med. Chem., 2013, 56, 6273-6277.
7. Antitumor activity of a duocarmycin analogue rationalised to be metabolically activated by cytochrome P450 1A1 in human transitional cell carcinoma of the bladder. M. Sutherland, P. Loadman, J. H. Gill, J. P. Laye, H. M. Sheldrake, N. Illingworth, M. N. Alandas, P. A. Cooper, M. Searcey, K. Pors, S. D. Shnyder, and L. H. Patterson. Mol. Cancer Ther. 2013, 12, 27-37.
8. Modification of the duocarmycin pharmacophore enables CYP1A1 targeting for biological activity. K. Pors, P. M. Loadman, S. D. Shnyder, M. Sutherland, H. M. Sheldrake, M. Guino, K. Kiakos, J. A. Hartley, M. Searcey and L. H. Patterson. Chem. Commun. 2011, 47, 12062-12064.
9. Chemical and Biological Explorations of the Family of CC-1065 and the Duocarmycin Natural Synthesis of the originally proposed structure of elatenyne and an enyne from Laurencia majuscula. H. M. Sheldrake, C. Jamieson, S. I. Pascu and J. W. Burton. Org. Biomol. Chem., 2009, 7, 238-252.

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Dr Jones studied Medical Biochemistry (BSc) and Molecular Toxicology (MRes), followed by a PhD in which he characterised the drug metabolism capacity of larval zebrafish, at the University of Birmingham.  Following post-doctoral research at the University of Sheffield (applying zebrafish models of Parkinson’s disease to drug screening) and the Hull York Medical School (University of Hull, investigating the bioactivities of natural products on human disease states), he held lecturing positions in biochemistry at the University of Hull, until joining the Institute of Cancer Therapeutics at the University of Bradford as a Lecturer in Drug Metabolism and Medical Biochemistry.

His research interests include:

• The pharmacokinetics of drugs and natural products
• The modulation of reactive oxygen and nitrogen species (RONS) signalling by natural products in ageing and disease states
• The application of physiologically-relevant compound exposures (concentration, duration and use of metabolites where possible) into in vitro mechanistic testing.
• Novel methods for the synthesis of drug metabolites for using in mechanistic studies and as analytical standards
• Improving the robustness of techniques for measuring RONS and oxidative stress

Selected Publications

1. Jones HS; Papageogiou M; Gordon A; Ehtesham; Javed Z; Wells E; Rigby A; Atkin SL; Courts FL; Sathyapalan T. Physiologically-relevant screening of polyphenol-rich commercial preparations for bioactivity in vascular endothelial cells, and application to human volunteers: a viable workflow and cautionary tale (2019). – Biochemical Pharmacology, 173, 113754.
2. Garrett AT; Dodd E; Biddlecombe V; Gleadall-Siddall D; Burke R; Shaw J; Bray J; Jones HS; Abt G; Gritt J. Effectiveness of Short-Term Heat Acclimation on Intermittent Sprint Performance With Moderately Trained Females Controlling for Menstrual Cycle Phase (2019).  Frontiers in Physiology, 10, 145
3. O’Doherty AF; Jones HS; Sathyapalan T, Ingle L; Carroll S. The effects of acute interval exercise and strawberry intake on postprandial lipaemia (2017). – Medicine and Science in Sports and Exercise, 49, 11, 2315-2323.
4. Jones HS; Gordon A; Magwenzi S; Naseem K; Atkin SL; Courts FL. The dietary flavonoid quercetin ameliorates angiotensin II-induced redox signalling imbalance in a human umbilical vein endothelilal cell model of endothelial dysfunction via ablation of p47^phox expression (2016) – Molecular Nutrition and Food Research, 60 (4), 787-797
5. Goodwin S; Allen S; Wells L; Whitham C; Jones HS; Rigby A; Sathyaplan T; Reid M; Atkin SL. Pilot investigation of a virtual gastric band intervention (2016) - International Journal of Clinical and Experimental Hypnosis, 64 (4).
6. Magawenzi S; Woodward C; Wraith KS; Abrurima A; Raslan Z; Jones HS; McNeil C; Wheatcroft S; Yuldasheva N; Febbriao M; Kearney M; Naseem K. Oxidised LDL activates blood platelets through CD36-NADPH oxidase-mediated inhibition of the cGMP/Protein kinase G signalling cascade (2015) – Blood, 125 (17), 2693-703.
7. Courts FL; Wells LK; Allen SK; Jones HS. Behaviour of Oligosaccharides in the gut.  Book chapter in Oligosaccharides: Food sources, biological roles and health implications (2014) – Nova publishers, ISBN: 978-1-62948-329-0.
8. David R; Jones HS; Hutchinson T; Winter M; Panter G; Chipman JK. Interference with xenobiotic metabolic activity by the commonly used vehicle solvents dimethylsufoxide and methanol in zebrafish (Danio rerio) larvae but not Daphnia magna. (2012)  – Chemosphere, 88 (8), 912-7.
9. Jones HS; Trollope H; Hutchinson T; Panter G; Chipman JK. Assessment of Ibuprofen metabolism by zebrafish larvae using Liquid Chromatography-Mass Spectrometry (LC-MS-MS) (2012) – Xenobiotica, 42 (11), 1069-75.
10. Jones HS; Panter G; Hutchinson T; Chipman JK. Oxidative and conjugative xenobiotic metabolism in zebrafish larvae in vivo (2010). Zebrafish, 7, 1, 23-30.

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Dr Nicholls graduated with a Bachelor of Biomedical Sciences (Hons) in 2007, and received his PhD from the Hudson Institute of Medical Research and Monash University (2012, Australia) on the development and endocrine regulation of the reproductive tract. Dr Nicholls then undertook postdoctoral research at the Whitehead Institute, based within the Massachusetts Institute of Technology (USA). In this research, Dr Nicholls described how embryonic cells of the germline – the precursors of both eggs and sperm – become committed to produce gametes in adulthood, and no other cell type. When this commitment fails to occur, these embryonic cells may instead form germ cell tumours of the gonads, one of the most common cancers of young children, and the most common cancer in men under 45 years of age.

Dr Nicholls has been awarded several honours, including the New Investigator Award from the Society for Reproductive Biology (Australia), and postdoctoral research fellowships awarded by the National Health and Medical Research Council (Australia) and the Hope Funds for Cancer Research (USA).

In 2020, Dr Nicholls joined the Faculty of Life Sciences and the Institute of Cancer Therapeutics.  In ongoing studies, Dr Nicholls uses a number of model organisms to explore how genetic and environmental factors influence the development of gonadal tumours from embryonic cells, and the  molecular pathways that govern the sensitivity of tumours to chemotherapy.

1. Nicholls PK et al. (2019) Mammalian germ cells are determined after PGC colonization of the nascent gonad. PNAS 116 (51), 25677-25687.

2. Nicholls PK et al (2019) Locating and characterizing a transgene integration site by nanopore sequencing. G3: Genes, Genomes, Genetics 9 (5), 1481-1486

3. Mikedis MM, Fan Y, Nicholls PK et al. (2020) DAZL mediates a broad translational program regulating expansion and differentiation of spermatogonial precursors. ELife 9:e56523

4. Dokshin GA, Davis GM, Sawle AD, Eldridge MD, Nicholls PK et al. (2020) GCNA interacts with Spartan and topoisomerase II to regulate genome stability. Developmental Cell 52 (1), 53-68.

5. Hu Y, Nicholls PK et al (2015) Licensing of primordial germ cells for gametogenesis depends on gernital ridge signaling. Plos Genetics 11 (3), e1005019.

Dr Ruiz graduated in Biochemistry from the University of Havana, Cuba. She completed her PhD in Advanced Materials and Nanotechnology at the Autonomous University of Madrid. Her PhD research project focused on developing magnetic nanoparticles for different biotechnological and biomedical applications.

Previously, Dr Ruiz held different postdoctoral positions across Cuba and Europe. In 2014 she joined the Centre for Advanced Studies in Cuba to investigate novel formulations of iron oxide nanoparticles and their toxicological evaluation in different in vitro and in vivo models. In 2016, she joined the University of East Anglia in Norwich as Senior Research Associate (Marie Skłodowska-Curie Fellow) to work in the DNA-TRAP EU funded project to develop a range of antimicrobial nanoformulations and assess their therapeutic efficacy in in vitro models. Later, she moved to the Molecular and Cellular Biology Institute in Strasbourg to be part of the Graphene Flagship project, the European Union's biggest scientific research initiative, to assess the pharmacological behaviour of different graphene-based materials and their innovative application in cancer treatment. In November 2018, she started at the School of Pharmacy at Queen’s University Belfast, where her research was focused on the development of smart nanocarriers for targeted cancer therapy, as well as engineering novel nanoformulations to detect and treat aggressive metastatic prostate cancer.

Currently, Dr Ruiz’s research focuses on the fabrication of multifunctional nanomaterials to target cancer and other diseases, developing novel nanomedicines for combinatory therapy and theragnostic applications and the safety evaluation of these nanomaterials applied to human health. Her long-term research career objective is to facilitate the translation of nanoparticle-based therapeutics from the lab to the clinic.

Recent Publications

1. L. Silva, A. Ruiz, A. Ali, S. Pereira, J. Seitsonen, J. Ruokolainen, C.R. Koffi, F. Furlong, J. Coulter, and W.T. Al-Jamal “Hypoxia-Targeted Cupric-Tirapazamine Liposomes Potentiate Radiotherapy in Prostate Cancer Spheroids” Int J Pharm. 2021 Sep 25;607:121018.
2. G. Ma, M. Severic, M. Barker, S. Pereira, A. Ruiz, Calvin Cheung and W.T. Al-Jamal “Dually targeted bioinspired nanovesicle delays advanced prostate cancer tumour growth in vivo” Acta Biomaterialia (2021) 15;134:559-575.
3. A. Ruiz, C. Martín and G. Reina “Does Black Phosphorus Hold Potential To Overcome Graphene Oxide? A Comparative Review Of Their Promising Application For Cancer Therapy” Nanoscale Advances (2021) 3, 4029-4036.
4. G. Ma, N. Kostevšek, I. Monaco, A. Ruiz, C.C.L. Cheung, S. Hudoklin, M.E. Kreft, H.A.F.M Hassan, J. Conyard, C. Hall, S. Meech, A.G. Mayes, I. Serša, M. Comes Franchini, and W.T. Al-Jamal “PD1 blockade potentiates the therapeutic efficacy of photothermally-activated and MRI-guided low temperature-sensitive magnetoliposomes.” Journal of Controlled Release (2021) 332, 419-433.
5. M. Severic; G. Ma; S. Pereira; A. Ruiz, C.C. Cheung, W.T. Al-Jamal “Genetically-engineered anti-PSMA exosome mimetics targeting advanced prostate cancer in vitro and in vivo” Journal of Controlled Release (2020) 330, 101-110.

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Dr. Wahajuddin joined the Institute of Cancer Therapeutics from India after serving as Principal Scientist and Associate professor (AcSIR) at the Pharmaceutics & Pharmacokinetics Division, CSIR- Central Drug Research Institute Lucknow. As well as being a registered pharmacist in India, he is a registered patent agent with the Indian patent office, New Delhi. He had perviously worked (2013-14) as a visiting scientist at UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, NC, USA and as Humboldt Research Fellow at University of Cologne Hospital's Centre for Pharmacology, Cologne, Germany (2018-19).

Dr. Wahajuddin has published more than 100 research papers in highly reputed peer reviewed international journals, nine book chapters and edited a book for Nova Science Publishers, New York, USA. He has also won many awards and accolades like the Young Scientist Award 2013-14 from the State Government of Uttar Pradesh India, the Shakuntala Amir Chand Prize 2019 for Young Scientist by the Indian Council of Medical Research (ICMR) Govt. of India, Young Pharmaceutical Analyst Award 2012 from the Indian Drug Manufacturer’s Association, DBT- Cutting-edge Research Enhancement & Scientific Training (DBT-CREST) Award 2011-12 from the Dept. of Biotech. Govt. of India, Junior Investigator Award 2017 from Safety Pharmacological Society USA and ISMAS Young Mass Spectroscopist Award 2013 from the Indian Society for Mass Spectrometry etc. He has been elected a member of the Global Young Academy under the aegis of German National Academy of Sciences, Leopoldina Halle, Germany, Indian National Young Academy of Sciences, National Academy of Sciences (India), National Academy of Medical Sciences (India) and was admitted as Fellow of Royal Society of Biology (UK), Royal Society of Chemistry (UK) and Higher Education Academy (UK). He is one of the co-leads of Science Diplomacy in South Asia, a working group of the Global Young Academy (2020-2021). He is editor/editorial board member of many reputed high-impact scientific journals like Current Pharmaceutical Design, Current Drug Delivery (Section Editor: Novel pharmaceutical strategies from nanotechniques for effective drug delivery), Recent Patents on Anti-Cancer Drug Discovery (Section Editor: Anti-infective Formulation), Frontiers in Nanotechnology (Review Editor for Biomedical Nanotechnology) and Pharmacognosy Magazine.

At ICT Bradford, Dr Wahajuddin is studying pharmacokinetics and biopharmaceutics of potential onco-therapies (in addition to marketed drugs/metabolites/natural products) and deciphering the molecular mechanism(s) of ADME/disposition thereof. 

Recent Publications 

1. Sharma M, Tiwari V, Chaturvedi S, Wahajuddin M, Shukla S, Panda JJ. (2022) Self-Fluorescent Lone Tryptophan Nanoparticles as Theranostic Agents Against Alzheimer's Disease. ACS Appl Mater Interfaces. PMID: 352630932.
2. Taneja I, Raghuvanshi A, Raju KSR, Awasthi P, Rashid M, Singh S, Goel A, Singh SP, Wahajuddin M (2020) Bioavailability, tissue distribution and excretion studies of a potential anti-osteoporotic agent, medicarpin, in female rats using validated LC-MS/MS method. J Pharm. Biomed. Anal. Volume 180, 20 February 2020, 112978. PMID 3185572
3. Anuj Garg, Kripal Bhalala, Devendra Singh Tomar, Wahajuddin M (2016). In-situ single pass intestinal permeability and pharmacokinetic study of developed Lumefantrine loaded solid lipid nanoparticles. International Journal of Pharmaceutics, 516, (1–2):120–130 PMID: 27989820
4. Shukla AK, Upadhyay SK, Mishra M, Saurabh S, Singh R, Singh H, Thakur N, Rai P, Pandey P Nair K N, Bhadauria S, Wahajuddin M, Singh S, Sharma S, Ranade SA, Tuli R, Singh PK. (2016) Expression of an insecticidal fern protein in cotton protects against whitefly. PMID: 27598229. Nature Biotechnology. 34,1046–1051
5. Raju KSR, Taneja I, Valicherla GR, Challagundla MK, GayenJR, Singh SP, Wahajuddin M§ (2015). No effect on pharmacokinetics of tamoxifen and 4-hydroxytamoxifen by multiple doses of red clover capsule in rats. Scientific Reports. 5:16126. PMID: 26530625

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Dr. Barnieh graduated with BSc (First Class Hon) in Biochemistry from the University of Ghana and went on to receive MSc (Distinction) in Cancer Pharmacology and PhD in Cancer Drug Discovery from the University of Bradford. His PhD was focused on the development of protease-activated peptide prodrugs of DNA Damage Response (DDR) inhibitors. In 2020, after the completion of his PhD, he undertook a post-doctoral fellowship as part of the ICT’s YCR programme, developing an LC-MS based assay to investigate the CYP-mediated metabolism of novel duocarmycin prodrugs, and additionally a high-throughput microplate ELISA assay for screening of both competitive polysialyltransferase inhibitors, and inhibitors of the NCAM-polyST protein-protein interaction.

Dr. Barnieh is currently UoB STARTER Research Fellow at the ICT, undertaking independent research, which is focused on understanding the tissue-specific glycosylation patterns of aminopeptidase N (APN/CD13), and the associated impact on the tissue-specific functions of this interesting protein. Additionally, he has keen interest in DDR inhibitors with particular emphasis on targeted tumour delivery of these agents.

Publications

1. Barnieh, F.M.; Loadman, P.M.; Falconer, R.A. “Is tumour-expressed aminopeptidase N (APN/CD13) structurally and functionally unique?” Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 2021, 1876, 188641.
2. Barnieh, F.M.; Loadman, P.M.; Falconer, R.A. “Progress towards a clinically-successful ATR inhibitor for cancer therapy. Current Research in Pharmacology and Drug Discovery 2021, 2, 100017.
3. Ortuzar, N.; Karu, K.; Presa D.; Morais, G.R.; Sheldrake, H.M; Shnyder, SD, Barnieh, F.M.; Loadman, P.M.; Patterson, L.H; Pors, K.; Searcey, M. Probing CYP bioactivation with chloromethylindoline bioprecursors derived from the duocarmycin family of compounds. Bioorg Med Chem 2021, 15;40:116167
4. Barnieh, F. M.; Race, A. D., Shnyder, S. D., Loadman, P. M., and Falconer, R. A. Investigating the mechanisms of cellular uptake and metabolism of ICT2588, an MT-MMP-activated prodrug. Cancer Res 2019 79, 350

Laurence is Emeritus Professor of Drug Discovery within the ICT with over 30 years’ experience of research in UK pharma and academia. Following on from his drug research and development experience at Fisons Pharmaceuticals (now AZ) and academic progression to Prof Pharmaceutical Chemistry at DeMontfort University, he went on to hold  key positions  as Prof Medicinal Chemistry and Head of Department of Pharmaceutical & Biological Chemistry at The University of London School of Pharmacy, and Director  of the Institute of Cancer Therapeutics, University of Bradford. Laurence has published over 250 papers and patents concerned with the discovery and development of new drugs, formulations and cell imaging reagents. Laurence is a co-inventor of the MMP-activated vascular disrupting agents and CYP450-activated ultrapotent cytotoxin prodrugs now assigned to InCanThera Plc, a spinout company of the ICT, of which he is a founding shareholder. His innovations have resulted in the establishment of BioStatus Ltd, BioTherics Ltd and BioSuspensions Ltd, three companies that he has a controlling influence in. Laurence is on the advisory board of the Empire Discovery Institute, NY, USA, and is also called on regularly to assess R&D grant and loan applications to major UK and international funding agencies. Laurence is a visiting professor to the Third Military Medical University, Chongqing and the Shanghai Institute of Materia Medica, CAS.  Laurence’s research group discovered Banoxantrone (AQ4N), the Phase II trial ready tumour hypoxia activated agent in progress by OncoTherics Poland Sp. z o.o.

Selected Publications

1. Y. He, T. Xiong, S. He, H. Sun, C. Huang, X. Ren, L. Wu ,L. H. Patterson  and J. Zhang, “Pulmonary Targeting Crosslinked Cyclodextrin Metal–Organic Frameworks for Lung Cancer Therapy”. (2020) Advanced  Functional Materials,   2004550.

2. Guo, X., J. R. Malcolm, M. M. Ali, G. R. Morais, S. D. Shnyder, P. M. Loadman, L. H. Patterson and R. A. Falconer (2020). "An efficient assay for identification and quantitative evaluation of potential polysialyltransferase inhibitors." Analyst, 145: 4512-4521

3. Xu, J., X. Ren, T. Guo, X. Sun, X. Chen, L. H. Patterson, H. Li and J. Zhang (2019). "NLG919/cyclodextrin complexation and anti-cancer therapeutic benefit as a potential immunotherapy in combination with paclitaxel." European Journal of Pharmaceutical Sciences 138: 105034.

4. Guo, Z., F. Wu, V. Singh, T. Guo, X. Ren, X. Yin, Q. Shao, P. York, L. H. Patterson and J. Zhang (2017). "Host-guest kinetic interactions between HP-β-cyclodextrin and drugs for prediction of bitter taste masking." Journal of Pharmaceutical and Biomedical Analysis 140: 232-238.

5. Nesbitt, H., N. M. Byrne, S. N. Williams, L. Ming, J. Worthington, R. J. Errington,                      L. H. Patterson, P. J. Smith, S. R. McKeown and D. J. McKenna (2017). "Targeting hypoxic prostate tumors using the novel hypoxia-activated prodrug OCT1002 inhibits expression of genes associated with malignant progression." Clinical Cancer Research 23(7): 1797-1808.

6. Shaheed, S. u., C. Tait, K. Kyriacou, J. Mullarkey, W. Burrill, L. H. Patterson, R. Linforth, M. Salhab and C. W. Sutton (2017). "Nipple aspirate fluid—A liquid biopsy for diagnosing breast health." PROTEOMICS–Clinical Applications 11(9-10): 1700015.

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Since being appointed as a lecturer and consequently senior lecturer and professor in Molecular Oncology and then as an anniversary chair professor in Molecular Pathology and Cancer Therapeutics in University of Bradford, Prof El-Tanani has made seminal contributions to the understanding of cancer metastasis - the spread of cancer from the primary tumour to distant organs and sites. Prof El-Tanani work, primarily focuses on tumour progression and metastasis, has changed many research paradigms in the field, as this complex process is responsible for the majority of cancer deaths. Once cancer has spread, current treatments ultimately fail for most patients. Furthermore, metastasis can be particularly insidious as it may develop after variable and unpredictable periods of tumour dormancy. Prof El-Tanani research program strives for a better understanding of metastasis and thus has the potential to improve cancer patient survival and quality of life. Prof El-Tanani work concentrates on two broad areas of cancer progression and metastasis. First, he has a major program aimed at understanding the biology of the cancer progression and metastatic process. This program uses animal models, novel-imaging approaches to “watch” the process, and molecular approaches to better understand how the process is regulated. Second, he has a major program focused on the secreted, integrin-binding protein osteopontin (OPN) and its target gene Ran GTPase (Ran). This program has complementary experimental and clinical arms, focused on learning how OPN, Ran and their target genes increase the metastatic potential of cancer cells, and on the development and uses of assays to measure OPN, Ran and their targets levels in tumours, which in turn could represent a valuable new predictive biomarker. Prof El-Tanani has shown that OPN and Ran contribute functionally to the malignant behaviour of cancer cells, and that measuring OPN and Ran levels in patients may provide clinically useful information.

1. El-Tanani, M.K., et al., Interferon-induced transmembrane 3 binds osteopontin in vitro: expressed in vivo IFITM3 reduced OPN expression. Oncogene, 2010. 29(5): p. 752-62.
2. El-Tanani, M.K., et al., Osteopontin can act as an effector for a germline mutation of BRCA1 in malignant transformation of breast cancer-related cells. Cancer Sci, 2010. 101(6): p. 1354-60.3.
3. Kurisetty, V.V., et al., RAN GTPase is an effector of the invasive/metastatic phenotype induced by osteopontin. Oncogene, 2008. 27(57): p. 7139-49.
4. Kurisetty, V.V., et al., Identification of genes differentially expressed between benign and osteopontin transformed rat mammary epithelial cells. BMC Res Notes, 2009. 2: p. 15. 
5. Yuen, H.F., et al., Ran GTPase promotes cancer progression via Met receptor-mediated downstream signaling. Oncotarget, 2016. 7(46): p. 75854-75864.
6. Yuen, H.F., et al., RanGTPase: a candidate for Myc-mediated cancer progression. J Natl Cancer Inst, 2013. 105(7): p. 475-88.

The scientific understanding of the role of Ran protein as an important therapeutic target and biomarker in cancer has been developed by himself and his team to the level of a platform capability. Ran protein is expressed in tumours which have high drug resistance and metastatic potential, so it is an excellent biomarker for prediction of patient drug response, early predict if the patient will develop metastasis and on patient survival. This is most relevant in the case of triple negative breast cancer, where conventional therapies or prognostic/predictive biomarkers are not available. Moreover, in non-small cell lung cancer, Ran expression can indicate the emergence of drug resistance. Ran itself is a therapeutic target for treatment of cancers with drug resistant or high metastatic potential. Thus, the Ran platform encompasses both biomarker technology for use in predictive/ companion diagnostics and targeted therapeutics. Prof El-Tanani has a growing portfolio of IP in this area and the various arms of the Ran platform are the subject of several grant applications including MRC, Breast Cancer Now and Wellcome Trust and others.

 7.Doherty, K.J., et al., RAN GTPase as a Target for Cancer Therapy: Ran Binding Proteins. Curr Mol Med, 2011.

8. Haggag, Y.A., et al., Nano-encapsulation of a novel anti-Ran-GTPase peptide for blockade of regulator of chromosome condensation 1 (RCC1) function in MDA-MB-231 breast cancer cells. Int J Pharm, 2017. 521(1-2): p. 40-53.

9. Yuen, H.F., et al., Ran is a potential therapeutic target for cancer cells with molecular changes associated with activation of the PI3K/Akt/mTORC1 and Ras/MEK/ERK pathways. Clin Cancer Res, 2012. 18(2): p. 380-91

It is also apparent that the pharmaceutical industry will benefit from an improved understanding of the mechanisms underlying Ran targets, as this could help improve the design of new drugs and identify new applications for existing agents. Therefore, disseminating results to a wide range of researchers and clinical staff is key to achieving maximum economic and societal benefit from my program. Prof El-Tanani has published more than 80 peer-reviewed papers, an average of 6 per year in high impact factor journals in recent years. Bibliometric analysis reveals that the research work carried out in his laboratory has high scientific impact and is frequently cited by many other researchers. Prof El-Tanani has been invited to present at numerous international, national, and local conferences.

Jason has a PhD in Chemistry from University of York and 20 years’ experience in R&D and business development in the pharmaceutical and chemical research services sector. Jason has extensive experience in business development and business management and is currently responsible for growing the commercial and collaborative grant funded revenues of a number of Research and Knowledge Transfer Centres across the Faculty of Life Sciences including Pharmaceutical Engineering Sciences, the Institute of Cancer Therapeutics and Centre for Chemical and Structural Analysis. Director and Business Manager for Lena Nanoceutics Ltd a University spin-in company.

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