Yr Athro Paul J Smith
Professor of Cancer Biology, Institute of Cancer and Genetics, School of Medicine
Trosolwg
I have been active in academic research in the fields of DNA repair, drug development, cytometry and imaging technologies with a focus on cancer research for more than 30 years. My research expertise and patents encompass the cell cycle, drug development, DNA topoisomerases and resistance to anticancer drugs – deploying imaging and flow cytometry technologies. I am considered as an opinion leader in cytometry.
Bywgraffiad
July 2013- : Science Director, Oncotherics Ltd
July 2013- : Emeritus Professor of Cancer Biology, School of Medicine, Cardiff University
1995-June 2013: Professor of Cancer Biology, School of Medicine, Cardiff University
1991-1995: Senior Scientist; MRC Clinical Oncology and Radiotherapeutics Unit, MRC Centre, Cambridge UK.
1982-1987: Non-Clinical Scientist. MRC Clinical Oncology and Radiotherapeutics Unit, MRC Centre, Cambridge UK. Career appointment from 1.6.87
1980-1982: Research Associate (with US National Cancer Institute) at AECL
1977-79: Research Fellow. Natural Sciences and Engineering Research Council. Atomic Energy of Canada Ltd. (AECL), Chalk River Nuclear Laboratories, Ontario, Canada.
1974-1977: PhD (Cellular Radiation Biology) Paterson Laboratories, Christie Hospital/Manchester University, UK
1971-1974: BSc (Hons; Medical Microbiology) Bristol University, UK
Anrhydeddau a Dyfarniadau
- 2013: Elected Fellow of The American Institute for Medical and Biological Engineering - representing the top 2% of the medical and biological engineering community, “for his seminal contributions to the development of drug screening technology”.
- 2012 Royal Society of Chemistry - Teamwork in Innovation Award (winners Smith and Biostatus Ltd) “for the worldwide exploitation of the molecular probe technology”, previous winners include Pfizer Global R & D team.
Aelodaethau proffesiynol
International Society for Advancement of Cytometry
President Elect (2008-2010); President (2010-2012); Past President (2012-2014);Conference Chair 2010;Council Member and Chair of the Scientific Advisory Committee for ISAC (1998-2010).
The International Society for Advancement of Cytometry (formerly International Society for Analytical Cytology) is a scientific and educational organization that leads the way in development of cytometry, transfer of new methodologies, and exchange of cutting-edge scientific and technical information in quantitative cell sciences.
Member: Association for Radiation Research
Safleoedd academaidd blaenorol
July 2013- : Emeritus Professor of Cancer Biology, School of Medicine, Cardiff University
1995-June 2013: Professor of Cancer Biology, School of Medicine, Cardiff University
1991-1995: Senior Scientist; MRC Clinical Oncology and Radiotherapeutics Unit, MRC Centre, Cambridge UK.
1982-1987: Non-Clinical Scientist. MRC Clinical Oncology and Radiotherapeutics Unit, MRC Centre, Cambridge UK. Career appointment from 1.6.87
Ymrwymiadau siarad cyhoeddus
Academic: To date, more than 200 formal seminars/lectures have been presented following invitations to various research institutes, meetings and courses both in the UK and overseas, or as proffered papers at scientific meetings and commercial meetings.
Pwyllgorau ac adolygu
External committe/panel experience:
Cross-discipline recognition and strategy development experience in UK Research Councils, 2003-2011:
- Member of Strategic Advisory Team for Engineering and Physical Sciences Research Council’s (EPSRC) Cross-disciplinary Interfaces Programme (CDIP)
- Member of Tools and Resources Strategy Panel for the Biotechnology and Biological Sciences Research Council (BBSRC)
- Medical Research Council (MRC) Expert Panel
- Member of the EPSRC Peer Review College.
- BBSRC Research Equipment panel member and member of the EPSRC Review College.
- EPSRC Basic Technology Mentor 2006-2010
- Panel chair for Research Councils UK Basic Technology Programme 2007
Advisory & Consultancy Experience in Clinical & Biomedical Sectors 1994-present:
- Consultant to Kudos Ltd and Theryte Ltd on anticancer drug development
- Foundation member of the Wales Cancer Trials Network
- Past co-chair of the Wales Cancer Trials Unit (WCTU) Translational Working Group
- Advisor to National Radiological Protection Board and the Health Protection Agency.
- Advisor to the International Atomic Energy Agency 1994
Non-profit Company Directorship 2008-present:
- Director of MediWales Ltd – national medical devices national forum and direct contributor to national science policy.
Cyhoeddiadau
2023
- Smith, P. J., McKeown, S. R. and Patterson, L. H. 2023. Targeting DNA topoisomerase IIα (TOP2A) in the hypoxic tumour microenvironment using unidirectional hypoxia-activated prodrugs (uHAPs). IUBMB Life 75(1), pp. 40-54. (10.1002/iub.2619)
2018
- Smith, P. J., Darzynkiewicz, Z. and Errington, R. J. 2018. Nuclear cytometry and chromatin organization. Cytometry Part A 93(8), pp. 771-784. (10.1002/cyto.a.23521)
2016
- Smith, P. J. 2016. Cytometric routes to single cell transcriptomics. Cytometry Part A 89(5), pp. 424-426. (10.1002/cyto.a.22869)
- Smith, P. J. 2016. EdU and BrdU incorporation resolve their differences. Cell Cycle 15(12), pp. 1527-1528. (10.1080/15384101.2016.1171654)
2013
- Al-Saraireh, Y. et al. 2013. Pharmacological inhibition of polysialyltransferase ST8SiaII modulates tumour cell migration. PLoS ONE 8(8), pp. e73366. (10.1371/journal.pone.0073366)
- Mart, R. J. et al. 2013. BH3 helix-derived biophotonic nanoswitches regulate cytochrome c release in permeabilised cells. Molecular BioSystems 9(11), pp. 2597-2603. (10.1039/c3mb70246d)
- Smith, P., Falconer, R. and Errington, R. 2013. Micro-community cytometry: sensing changes in cell health and glycoconjugate expression by imaging and flow cytometry. Journal of Microscopy 251(2), pp. 113-122. (10.1111/jmi.12060)
- Errington, R. J., Chappell, S. C., Khan, I. A., Marquez Almuina, N., Wiltshire, M., Griesdoorn, V. D. and Smith, P. J. 2013. Time-lapse microscopy approaches to track cell cycle and lineage progression at the single-cell level. Current Protocols in Cytometry 64(12.4) (10.1002/0471142956.cy1204s64)
- Becker, H. et al. 2013. Multivariate analysis of apoptotic markers versus cell cycle phase in living human cancer cells by microfluidic cytometry. Proceedings of SPIE 8615, pp. 86150W. (10.1117/12.2001474)
- Smith, P. J., Wiltshire, M., Chappell, S. C., Cosentino, L., Burns, P. A., Pors, K. and Errington, R. J. 2013. Kinetic analysis of intracellular Hoechst 33342-DNA interactions by flow cytometry: misinterpretation of side population status?. Cytometry Part A 83A(1), pp. 161-169. (10.1002/cyto.a.22224)
- Akagi, J. et al. 2013. Real-time cell viability assays using a new anthracycline derivative DRAQ7®. Cytometry Part A 83A(2), pp. 227-234. (10.1002/cyto.a.22228)
- Smith, P. J. et al. 2013. NCAM polysialylation during adherence transitions: live cell monitoring using an antibody-mimetic EGFP-endosialidase and the viability dye DRAQ7. Cytometry Part A 83A(7), pp. 659-671. (10.1002/cyto.a.22306)
2011
- Atari, M. I., Chappell, M. J., Errington, R. J., Smith, P. J. and Evans, N. D. 2011. Kinetic modelling of the role of the aldehyde dehydrogenase enzyme and the breast cancer resistance protein in drug resistance and transport. Computer Methods and Programs in Biomedicine 104(2), pp. 93-103. (10.1016/j.cmpb.2010.06.008)
- Khan, I. A. et al. 2011. Interoperability of time series cytometric data: A cross platform approach for modeling tumor heterogeneity. Cytometry Part A 79A(3), pp. 214-226. (10.1002/cyto.a.21023)
- Rees, P., Brown, M. R., Summers, H. D., Holton, M. D., Errington, R. J., Chappell, S. C. and Smith, P. J. 2011. A transfer function approach to measuring cell inheritance. BMC Systems Biology 5, article number: 31. (10.1186/1752-0509-5-31)
- Fricke, T. et al. 2011. Chemical synthesis of cell-permeable apoptotic peptides from in vivo produced proteins. Bioconjugate Chemistry 22(9), pp. 1763-1767. (10.1021/bc200338u)
- Summers, H. D., Rees, P., Holton, M. D., Rowan Brown, M., Chappell, S. C., Smith, P. J. and Errington, R. J. 2011. Statistical analysis of nanoparticle dosing in a dynamic cellular system. Nature Nanotechnology 6(3), pp. 170-174. (10.1038/nnano.2010.277)
- Davies, L. C., Rosas, M., Smith, P. J., Fraser, D. J., Jones, S. A. and Taylor, P. R. 2011. A quantifiable proliferative burst of tissue macrophages restores homeostatic macrophage populations after acute inflammation. European Journal of Immunology 41(8), pp. 2155-2164. (10.1002/eji.201141817)
2010
- Brown, M. R., Summers, H. D., Rees, P., Smith, P. J., Chappell, S. C. and Errington, R. J. 2010. Flow-based cytometric analysis of cell cycle via simulated cell populations. PLOS Computational Biology 6(4), article number: e1000741. (10.1371/journal.pcbi.1000741)
- Errington, R. J. et al. 2010. Single cell nanoparticle tracking to model cell cycle dynamics and compartmental inheritance. Cell Cycle 9(1), pp. 121-130. (10.4161/cc.9.1.10246)
- Brown, M. R. et al. 2010. Long-term time series analysis of quantum dot encoded cells by deconvolution of the autofluorescence signal. Cytometry Part A 77A(10), pp. 925-932. (10.1002/cyto.a.20936)
2009
- Smith, P. J., Furon, E., Wiltshire, M., Campbell, L., Feeney, G. P., Snyder, R. D. and Errington, R. J. 2009. ABCG2-Associated Resistance to Hoechst 33342 and Topotecan in a Murine Cell Model with Constitutive Expression of Side Population Characteristics. Cytometry Part A 75A(11), pp. 924-933. (10.1002/cyto.a.20800)
- Smith, P. J., Khan, I. A. and Errington, R. J. 2009. Cytomics and cellular informatics - coping with asymmetry and heterogeneity in biological systems. Drug Discovery Today 14(5-6), pp. 271-277. (10.1016/j.drudis.2008.11.012)
- Holton, M. D., Silvestre, O., Errington, R. J., Smith, P. J., Matthews, D. R., Rees, P. and Summers, H. D. 2009. Stroboscopic fluorescence lifetime imaging. Optics Express 17(7), pp. 5205-5216. (10.1364/OE.17.005205)
- Smith, P. J. and Patterson, L. 2009. Anthraquinone and its derivatives. 7605280 [Patent].
- Smith, P. J., Errington, R. J., Summers, H. and Chappell, S. C. 2009. Microtrench and tumour proliferation assay. WO/2009/095666 [Patent].
- Silvestre, O., Holton, M. D., Summers, H. D., Smith, P. J. and Errington, R. J. 2009. Hollow fiber: a biophotonic implant for live cells. Presented at: Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues VII, San Jose, CA, USA, 26-28 January 2009 Presented at Farkas, D. L., Nicolau, D. V. and Leif, R. C. eds.Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues VII. Proceedings of the SPIE Vol. 7182. Bellingham, WA: SPIE, (10.1117/12.809391)
2008
- Smith, P. J. and Errington, R. J. 2008. Dissecting the Cell Cycle: Loss of Genomic Integrity and Escape from Senescence [Abstract]. Cytometry Part B Clinical Cytometry 74B(6), pp. 390. (10.1002/cyto.b.20462)
- Smith, P. J., Wiltshire, M., Furon, E., Beattie, J. H. and Errington, R. J. 2008. Impact of overexpression of metallothionein-1 on cell cycle progression and zinc toxicity. American Journal of Physiology - Cell Physiology 295(5), pp. C1399-C1408. (10.1152/ajpcell.00342.2008)
- Cheung, S. Y. A., Evans, N. D., Chappell, M. J., Godfrey, K. R., Smith, P. J. and Errington, R. J. 2008. Exploration of the intercellular heterogeneity of topotecan uptake into human breast cancer cells through compartmental modelling. Mathematical Biosciences 213(2), pp. 119-134. (10.1016/j.mbs.2008.03.008)
- Chappell, M. J. et al. 2008. A coupled drug kinetics-cell cycle model to analyse the response of human cells to intervention by topotecan. Computer Methods and Programs in Biomedicine 89(2), pp. 169-178. (10.1016/j.cmpb.2007.11.002)
- Vojnovic, B., Barber, P., Pope, I., Smith, P. J. and Errington, R. J. 2008. Detecting objects. WO/2008/090330 [Patent].
- Smith, P. J., Patterson, L. and Errington, R. J. 2008. Gel formulations and uses thereof. 20080182287 [Patent].
- Summers, H. D., Errington, R. J., Smith, P. J., Matthews, D. R. and Leary, J. F. 2008. Cytometric biochips with optically active surfaces for spatial engineering of fluorescence excitation. Presented at: Microfluidics, BioMEMS, and Medical Microsystems VI, San Jose, CA, USA, 21-22 January 2008 Presented at Wang, W. and Vauchier, C. eds.Microfluidics, BioMEMS, and Medical Microsystems VI (Proceedings Volume). Proceedings of the SPIE Vol. 6886. Bellingham, WA: SPIE, (10.1117/12.763645)
- Summers, H. D., Errington, R. J., Smith, P. J., Chappell, S. C., Rees, P., Brown, M. R. and Leary, J. F. 2008. Cell-population tracking using quantum dots in flow cytometry. Presented at: Nanoscale Imaging, Sensing, and Actuation for Biomedical Applications V, San Jose, CA, USA, 21-23 February 2008 Presented at Cartwright, A. N. and Nicolau, D. V. eds.Nanoscale Imaging, Sensing, and Actuation for Biomedical Applications V. Proceedings of the SPIE Vol. 6865. Bellingham, WA: SPIE pp. 68650L., (10.1117/12.763602)
2007
- Smith, P. J. et al. 2007. Mitotic bypass via an occult cell cycle phase following DNA topoisomerase II inhibition in p53 functional human tumor cells. Cell Cycle 6(16), pp. 2071-2081. (10.4161/cc.6.16.4585)
- Khan, I. A., Husemann, P., Campbell, L., White, N. S., White, R. J., Smith, P. J. and Errington, R. J. 2007. ProgeniDB - A novel cell lineage database for generation associated phenotypic behavior in cell-based assays. Cell Cycle 6(7), pp. 868-874. (10.4161/cc.6.7.4045)
- Morris, D. et al. 2007. Development of an optical biochip for the analysis of cell environment sensitivity. Presented at: Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues V, San Jose, CA, USA, 20 January 2007 Presented at Farkas, D. L., Leif, R. C. and Nicolau, D. V. eds.Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues V. Proceedings of SPIE Vol. 6441. Bellingham, WA: SPIE pp. 64410V., (10.1117/12.700052)
- Njoh, K. et al. 2007. Live cell tracking on an optical biochip platform. Presented at: Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues V, San Jose, CA, USA, 20 January 2007 Presented at Farkas, D. L., Leif, R. C. and Nicolau, D. V. eds.Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues V. Proceedings of SPIE Vol. 6441. Bellingham, WA: SPIE pp. 64410X., (10.1117/12.698935)
- Matthews, D. R. et al. 2007. A fluorescence biochip with a plasmon active surface. Presented at: Plasmonics in Biology and Medicine IV, San Jose, CA, USA, 20 January 2007 Presented at Vo-Dinh, T. and Lakowicz, J. R. eds.Plasmonics in Biology and Medicine IV. Proceedings of SPIE Vol. 6450. Bellingham, WA: SPIE pp. 645006., (10.1117/12.698948)
- Chong, E. Z., Matthews, D. R., Summers, H. D., Njoh, K., Errington, R. J. and Smith, P. J. 2007. Development of FRET-Based assays in the Far-Red using CdTe quantum dots. Journal of Biomedicine and Biotechnology 2007, article number: 54169. (10.1155/2007/54169)
2006
- Njoh, K. L. et al. 2006. Spectral analysis of the DNA targeting bisalkylaminoanthraquinone DRAQ5 in intact living cells. Cytometry Part A 69A(8), pp. 805-814. (10.1002/cyto.a.20308)
- Matthews, D. R. et al. 2006. Technique for Measurement of Fluorescence Lifetime by use of Stroboscopic Excitation and Continuous-Wave Detection. Applied Optics 45(9), pp. 2115-2123. (10.1364/AO.45.002115)
2005
- Pors, K., Plumb, J. A., Brown, R., Teesdale-Spittle, P., Searcey, M., Smith, P. J. and Patterson, L. H. 2005. Development of nonsymmetrical 1,4-disubstituted anthraquinones that are potently active against cisplatin-resistant ovarian cancer cells. Journal of Medicinal Chemistry 48(21), pp. 6690-6695. (10.1021/jm050438f)
- Errington, R. J., Ameer-Beg, S. M., Vojnovic, B., Patterson, L. H., Zloh, M. and Smith, P. J. 2005. Advanced microscopy solutions for monitoring the kinetics and dynamics of drug-DNA targeting in living cells. Advanced Drug Delivery Reviews 57(10), pp. 153-167. (10.1016/j.addr.2004.05.005)
2004
- Marquez, N., Chappell, S. C., Sansom, O. J., Clarke, A. R., Teesdale-Spittle, P., Errington, R. J. and Smith, P. J. 2004. Microtubule stress modifies intra-nuclear location of Msh2 in mouse embryonic fibroblasts. Cell Cycle 3, pp. 662-671.
2003
- Marquez, N., Chappell, S. C., Sansom, O. J., Clarke, A. R., Errington, R. J., Smith, P. J. and Court, J. 2003. Single cell tracking reveals that Msh2 is a key component of an early-acting DNA damage-activated G2 checkpoint. Oncogene 22(48), pp. 7642-7648. (10.1038/sj.onc.1206876)
- Davis, T. et al. 2003. Telomere-based proliferative lifespan barriers in Werner-syndrome fibroblasts involve both p53-dependent and p53-independent mechanisms. Journal of Cell Science (JCS) 116(7), pp. 1349-57. (10.1242/jcs.00331)
2002
- Rees, D. A., Lewis, M. D., Lewis, B. M., Smith, P. J., Scanlon, M. F. and Ham, J. 2002. Adenosine-regulated cell proliferation in pituitary folliculostellate and endocrine cells: differential roles for the A(1) and A(2B) adenosine receptors. Endocrinology 143(6), pp. 2427-2436. (10.1210/en.143.6.2427)
2000
- Smith, P. J. et al. 2000. Characteristics of a novel deep red/infrared fluorescent cell-permeant DNA probe, DRAQ5, in intact human cells analyzed by flow cytometry, confocal and multiphoton microscopy. Cytometry 40(4), pp. 280-291. (10.1002/1097-0320(20000801)40:4<280::AID-CYTO4>3.0.CO;2-7)
1999
- Smith, P. J., Wiltshire, M., Davies, S., Patterson, L. H. and Hoy, T. 1999. A novel cell permeant and far red-fluorescing DNA probe, DRAQ5, for blood cell discrimination by flow cytometry. Journal of Immunological Methods 229(1-2), pp. 131-139. (10.1016/S0022-1759(99)00116-7)
1997
- Smith, P. J., Desnoyers, R., Blunt, N., Giles, Y., Patterson, L. H. and Watson, J. V. 1997. Flow cytometric analysis and confocal imaging of anticancer alkylaminoanthraquinones and their N-oxides in intact human cells using 647-nm krypton laser excitation. Cytometry 27(1), pp. 43-53. (10.1002/(SICI)1097-0320(19970101)27:1<43::AID-CYTO6>3.0.CO;2-M)
Addysgu
Cancer biology module ME3034 Lectures on: Cancer Biology of the Cell Cycle; Chemotherapy
My laboratory has been recognised for its state-of-the-art flow cytometric and imaging studies as applied to problems in cancer biology. A focus has been DNA damage responses in human tumour cells and linkage with cell cycle control. Current work is centred on the cell cycle as a target for anticancer agents and the development of technologies to support drug discovery. We have links with drug development groups with a long term aim of progressing agents through to trials. An important aspect of this is the development of mathematical modelling for cellular heterogeneity and drug responses with the University of Warwick.
Our technology development studies have focused on optical biochips incorporating microelectrode structures to allow the electrokinetic actuation of cells in AC electric fields - for example by dielectrophoresis (DEP). We have exploited basic dielectrophoresis (DEP) and fluidic phenomena on our biochip platforms to provide solutions for cell processing and analysis supported by genetic algorithms to resolve DEP data. Such probless DEP profiling of cells provides opportunities for the evaluation and sorting of cells used in tissue engineering applications.
Research impacts
In 2001 I co-founded and became a Director of Biostatus Ltd (www.biostatus.com) to exploit dye technolgy invented at Cardiff University
- 1999-2006 I invented a novel class of far-red fluorescent dyes – the lead dye DRAQ5™ is now used in over 3,500 research, pharmaceutical and clinical organisations world-wide in a wide range of laboratory assays, transforming practice in clinical, commercial and research sectors.
- The award-winning start-up company Biostatus Ltd with support under a BBSRC SBRI grant has undertaken further reserach and product development. The succes of this activity has been to enable export revenue, job creation, futher funding of UK academic research and the creation of new startups: 2009 Oncotherics Ltd (Registered No.06940617) - development of anticancer pro-drug technology for the treatrment of pancreatic cancer; 2008 Biosuspensions Ltd (Registered No.06780280) - development of new drug delivery technology.