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Dr Simon Scott

Lecturer in Molecular Biology

Medway School of Pharmacy

 

Following completion of his PhD, Simon conducted postdoctoral studies in virology in Cambridge and Amsterdam, before entering his current research field of cancer gene therapy, working at institutes in Manchester and London. He then took up a faculty position at Wayne State University in Michigan, USA, for three years, where he continued his research and taught on various postgraduate courses. He returned to the UK in 2004, working briefly at Sheffield University and joining the Medway School of Pharmacy in June 2006.

Specialist areas
Simon teaches molecular biology, genetics, virology, vaccines/antiviral drugs, cancer biology and gene therapy on the MPharm degree course at the School, both in the classroom and laboratory. He will also teach on the new MSc Applied Drug Discovery course, covering subjects such as molecular pharmacology, laboratory skills, study design, translational virology and supervision of lab-based research projects . He was directly involved in the design and setup of the custom-refurbished biological sciences laboratories at MSoP, and annually supervises a number of 4th year research project students in the labs. He has supervised a successful MSc student on a gene therapy/molecular biology 3 year research project, and is now a supervisor for two PhD students studying different RNA viruses. back to top

Simon’s research is focussed on developing viral and non-viral gene therapy vector systems both for the treatment of solid tumours and, more recently, cardiovascular disease. He has also initiated an internal collaboration with Dr Nigel Temperton to investigate the use of non-pathogenic virus ‘pseudotypes’ to study pathogenic RNA in a new purpose-built laboratory (the Viral Pseudotype Unit or VPU).

The anti-cancer vectors have been designed to be activated by conventional cancer treatments, such as radiation and chemotherapeutic agents. Furthermore, as hypoxia (low oxygen) is a characteristic feature of the physiology of solid tumours, the vectors have additionally been made hypoxia-responsive. The therapeutic modality uses ‘suicide genes’, which, once expressed in target tumour cells, lead to either direct cell death or kill neighbouring tumour cells via ‘the bystander effect’. Frequently the therapeutic mechanism relies on the expressed gene producing an enzyme that can convert a non-toxic prodrug to a cytotoxin.

Current Projects

Simon’s work is involved in investigated potent new genes/prodrugs, particularly those which engender substantial bystander effects, and especially those which enhance tumour cell radiosensitivity. Another major focus, has been studying the effects of different radiation sources (e.g. X-rays, neutrons, radioisotopes) on the activation process, with a view to incorporation of the gene therapy into existing radiation treatment regimens. Much effort has also been put into developing gene expression amplification and maintenance systems (e.g. using Cre recombinase/lox mechanisms) to maximise therapeutic output and effective treatment ‘window’. Lastly, Simon is also investigating the potential for delivery of the therapeutic vectors using a variety of schemes. These include plasmids, recombinant viruses (e.g. adenovirus, lentivirus), specific human cell types (e.g. macrophages, osteoclasts) and biomimetic polymer vesicles. Much of this current work is involves both national and international collaborations with other leading scientists in the field.

A further collaboration with Dr Paul Kingston at the University of Manchester was awarded funding by the British Heart Foundation in 2011, and involves engineering plasmid vectors to maximise the level and duration of therapeutic gene expression in smooth muscle cells, such as those that line coronary arteries. These vessels often undergo restenosis following common cardiovascular treatment interventions such as balloon angioplasty, causing further blockage. It is hoped that the introduction of therapeutic plasmid vectors from a stent platform will substantially reduce this process. The vectors developed will be tested in suitable blood vessel models. A postdoctoral scientist, Dr Helen Leech, is employed at Kent to produce the novel vector constructs.

lab 1Lastly, work in the new VPU involves the production of non-pathogenic ‘pseudotype’ lentiviruses bearing specific ‘envelope’ glycoproteins from pathogenic RNA viruses, currently including; influenza, Japanese Encephalitis, Crimean-Congo Haemorrhagic Fever, West Nile and Chandipura viruses. These can be used in serological studies to monitor new virus outbreaks worldwide, assess vaccine efficacy and identify novel antiviral compounds. and provide information on virus/cell interactions that may provide further antiviral drug targets. Dr Scott supervises two PhD students (Francesca Ferrara, Stuart Mather) producing and studying virus pseudotypes in the VPU.

 

 

 

Simon's research is currently funded by MSoP, National Institutes of Health (USA), British Heart Foundation and the Slovenian Research Agency.

At the end of 2012 Dr Scott and colleagues published the first paper describing the production of  equine influenza pseudotypes, and their subsequent use for serological screening. This study was quickly picked up and passed on by the Health Protection Agency via social media, and will be presented at the Society for General Microbiology and International Symposium on Neglected Influenza Viruses in Spring 2013.

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Selected publications

  • Rebecca Kinsley, Simon D. Scott and Janet M. Daly. Controlling equine influenza: traditional to next generation serological assays. Veterinary Microbiology (DOI: 10.1016/j.vetmic.2016.03.006)​.
  • Temperton NJ, Wright E & Scott SD. ‘Retroviral Pseudotypes – From Scientific Tools to Clinical Utility’ review article has been published online in the Encyclopedia of Life Sciences (DOI: 10.1002/9780470015902.a0021549.pub2).
  • Greife A1, Tukova J, Steinhoff C, Scott SD, Schulz WA, Hatina J. Establishment and characterization of a bladder cancer cell line with enhanced doxorubicin resistance by mevalonate pathway activation. Tumour Biol. 2015 Jan 8. [Epub ahead of print]
  • Mather ST, Wright E, Scott SD, Temperton NJ. Lyophilisation of influenza, rabies and Marburg lentiviral pseudotype viruses for the development and distribution of a neutralisation -assay-based diagnostic kit. J Virol Methods. 2014 Oct 5;210C:51-58. doi: 10.1016/j.jviromet.2014.09.021.
  • Mather S, Scott S, Temperton N, Wright E, King B & Daly J. Current progress with serological assays for exotic emerging / re-emerging viruses. Future Virology, August 2013, Vol. 8, No. 8, Pages 745-755.
  • Francesca Ferrara, Eleonora Molesti, Eva Böttcher-Frieberthäuser, Giovanni Cattoli, Davide Corti, Simon D Scott and Nigel J Temperton. The human Transmembrane Protease Serine 2 is necessary for the production of Group 2 influenza A virus pseudotypes. J Mol Genet Med 2013, Vol 7, 309-314
  • Simon Scott, Eleonora Molesti, Nigel Temperton, Francesca Ferrara, Eva Böttcher-Friebertshäuser and Janet Daly. The use of equine influenza pseudotypes for serological screening. J Mol Genet Med 2012, Vol 6, 304-308
  • Muthana M, Giannoudis A, Scott SD, Fang HY, Coffelt SB, Morrow FJ, Murdoch C, Burton J, Cross N, Burke B, Mistry R, Hamdy F, Brown NJ, Georgopoulos L, Hoskin P, Essand M,Lewis CE, Maitland NJ. Use of macrophages to target therapeutic adenovirus to human prostate tumors. Cancer Research 71:1805-1815. (2011)
  • Hingorani M, White CL, Merron A, Peerlinck I, Gore ME, Slade A, Scott SD, Nutting CM, Pandha HS, Melcher AA, Vile RG, Vassaux G, Harrington KJ. Inhibition of repair of radiation-induced DNA damage enhances gene expression from replication-defective adenoviral vectors. Cancer Research 68:9771-8. (2008)
  • Muthana M, Scott SD, Farrow N, Morrow F, Murdoch C, Grubb S, Brown N, Dobson J, Lewis CE. A novel magnetic approach to enhance the efficacy of cell-based gene therapies. Gene Therapy 15:902-910. (2008)
  • Coulter JA, McCarthy HO, Worthington J, Robson T, Scott S, Hirst DG. The radiation-inducible pE9 promoter driving inducible nitric oxide synthase radiosensitises hypoxic tumour cells to radiation. Gene Therapy 15:495-503. (2008)

Book chapters & Review articles

  • Temperton NJ, Wright E, Scott S. Retroviral Pseudotypes - from scientific tools to clinical utility. Encyclopaedia of Life Sciences. 2015; In Press
  • Greco O & Scott S. Tumor Hypoxia and Targeted Gene Therapy. International Review of Cytology 257: 181-212. (2007).
  • The Tumor Environment as a Target for Therapy. (S.D. Scott & O. Greco Editors.). Frontiers in Bioscience 12:3406-4076. (2007)
  • Greco O, Marples B, Wilson GD, Joiner MC & Scott SD. Radiation-induced Gene Therapy. Radiat. Res. 163:707. (2005)
  • Marples B, Greco O, Joiner MC & Scott SD. Radiogenetic Therapy using Radiation-Responsive Gene Promoters. Front. Med. Chem. 2 (1):317-330. (2005).
  • Scott SD & Greco O. Radiation and hypoxia inducible gene therapy systems. Cancer Metastasis Rev. 23:269-276. (2004)
  • Scott SD & Marples B. Radiation-mediated gene therapy. In Methods in Molecular Medicine, Suicide Gene Therapy: Methods and Protocols for Cancer pp389-402 (C.J. Springer Ed.). Humana Press, New Jersey (2003).
  • Greco, O, Marples, B, Jojner, MC, Scott SD. How to overcome (and exploit) tumor hypoxia for targeted gene therapy. J Cell Physiol. 97:312-325. (2003)
  • Greco O, Scott SD, Marples B & Dachs G. Cancer gene therapy: Delivery, delivery, delivery. Front. Biosci. 7:1516-1524. (2002)
  • Marples B, Greco O, Joiner MC, Scott SD. Molecular approaches to chemo-radiotherapy. Eur. J. Cancer. 38:231-239. (2002).

Patents

  • “Viral vaccines”
    Patent Application Nos. 081932 (US) 8821441.6 (UK), 1988. Licensed worldwide.

  • “Radiation-mediated gene therapy”
    Patent Application No. 9810423.5 (UK), 1998.
    PCT Application No. PCT/GB99/03162, 1999. Licensed in Europe, Canada, Australia, New Zealand, India. US license application filed 2001.

 

Full research paper publication list

View...

  • Rebecca Kinsley, Simon D. Scott and Janet M. Daly. Controlling equine influenza: traditional to next generation serological assays. Veterinary Microbiology (DOI: 10.1016/j.vetmic.2016.03.006)​.
  • Temperton NJ, Wright E & Scott SD. ‘Retroviral Pseudotypes – From Scientific Tools to Clinical Utility’ review article has been published online in the Encyclopedia of Life Sciences (DOI: 10.1002/9780470015902.a0021549.pub2).
  • Greife A1, Tukova J, Steinhoff C, Scott SD, Schulz WA, Hatina J. Establishment and characterization of a bladder cancer cell line with enhanced doxorubicin resistance by mevalonate pathway activation. Tumour Biol. 2015 Jan 8. [Epub ahead of print]
  • Mather ST, Wright E, Scott SD, Temperton NJ. Lyophilisation of influenza, rabies and Marburg lentiviral pseudotype viruses for the development and distribution of a neutralisation -assay-based diagnostic kit. J Virol Methods. 2014 Oct 5;210C:51-58. doi: 10.1016/j.jviromet.2014.09.021.
  • Mather S, Scott S, Temperton N, Wright E, King B & Daly J. Current progress with serological assays for exotic emerging / re-emerging viruses. Future Virology, August 2013, Vol. 8, No. 8, Pages 745-755.
  • Francesca Ferrara, Eleonora Molesti, Eva Böttcher-Frieberthäuser, Giovanni Cattoli, Davide Corti, Simon D Scott and Nigel J Temperton. The human Transmembrane Protease Serine 2 is necessary for the production of Group 2 influenza A virus pseudotypes. J Mol Genet Med 2013, Vol 7, 309-314
  • Simon Scott, Eleonora Molesti, Nigel Temperton, Francesca Ferrara, Eva Böttcher-Friebertshäuser and Janet Daly. The use of equine influenza pseudotypes for serological screening. J Mol Genet Med 2012, Vol 6, 304-308
  • Muthana M, Giannoudis A, Scott SD, Fang HY, Coffelt SB, Morrow FJ, Murdoch C, Burton J, Cross N, Burke B, Mistry R, Hamdy F, Brown NJ, Georgopoulos L, Hoskin P, Essand M,Lewis CE, Maitland NJ. Use of macrophages to target therapeutic adenovirus to human prostate tumors. Cancer Research 71:1805-1815. (2011)
  • Hingorani M, White CL, Merron A, Peerlinck I, Gore ME, Slade A, Scott SD, Nutting CM, Pandha HS, Melcher AA, Vile RG, Vassaux G, Harrington KJ. Inhibition of repair of radiation-induced DNA damage enhances gene expression from replication-defective adenoviral vectors. Cancer Research 68:9771-8. (2008)
  • Muthana M, Scott SD, Farrow N, Morrow F, Murdoch C, Grubb S, Brown N, Dobson J, Lewis CE. A novel magnetic approach to enhance the efficacy of cell-based gene therapies. Gene Therapy 15:902-910. (2008)
  • Coulter JA, McCarthy HO, Worthington J, Robson T, Scott S, Hirst DG. The radiation-inducible pE9 promoter driving inducible nitric oxide synthase radiosensitises hypoxic tumour cells to radiation. Gene Therapy 15:495-503. (2008)
  • Greco O, Joiner MC, Doleh A, Powell AD, Hillman G & Scott SD (2006). Hypoxia- and radiation-activated Cre/LoxP molecular switch vectors for gene therapy of solid tumors. Gene Therapy 13:206-215.
  • Lipnik K, Greco O, Scott SD, Knapp E, Rosenfellner D, Mayrhofer E, Günzburg WH, Salmons B (2006). Hypoxia- and Radiation-inducible, breast cell-specific targeting of retroviral vectors. Virology 369:121-133.
  • Greco O, Powell T, Joiner MC, Marples B & Scott SD. Synthetic promoters containing CArG elements from the Egr-1 gene are activated by neutron irradiation, cisplatin and doxorubicin. Cancer Gene Therapy 12: 655-662 (2005).
  • Worthington J, Robson T, Scott SD & Hirst D (2005). Evaluation of a synthetic CArG promoter for nitric oxide synthase gene therapy of cancer. Gene Therapy 12:1417-1423.
  • Greco O, Joiner MC, Doleh A & Scott SD (2005). VP22: intercellular transport for suicide gene therapy under oxic and hypoxic conditions. Gene Therapy 12:974-979.
  • Chadderton N, Cowen RL, Robinson S, Greco O, Scott SD, Stratford IJ, Patterson AV & Williams KJ. Dual responsive promoters target therapeutic gene expression to radiation-resistant hypoxic tumour cells. Radiat.Oncol. Biol. Phys. 62:213-222. (2005)
  • Scott SD, Joiner MC & Marples B (2002). Optimizing radiation-responsive gene promoters for radiogenetic cancer therapy. Gene Therapy 9: 1396-1402.
  • Greco O, Marples B, Dachs GU, Williams KJ, Patterson AV & Scott SD (2002). Novel chimeric gene promoters responsive to hypoxia and ionizing radiation. Gene Therapy 9: 1403-1411.
  • Collis SJ, Tighe A, Scott SD, Roberts SA, Hendry JH & Margison GP. Ribozyme-minigene mediated RAD51 down-regulation increases radiosensitivity of human prostate cancer cells. Nuc. Acids Res. 29:1534-1538. (2001)
  • Scott SD, Marples B, Hunter RD, Howell A, Lashford L, Embleton MJ, Hendry JH & Margison GP (2000). A radiation-controlled molecular switch for use in cancer gene therapy. Gene Therapy 7:1121-1125.
  • Marples B, Scott SD, Embleton MJ, Lashford L, Hendry JH & Margison GP(2000). Development of synthetic promoters for radiation-mediated gene therapy. Gene Therapy7:511-517.
  • Snijders PJF, Top B, Scott SD, Meijer CJLM & Walboomers JMM. Analysis of p53 status in tonsillar carcinomas associated with human papillomavirus. J. Gen. Virol., 75:2769-2775. (1994).
  • Ross LJN, Tyers P, Pastorek J, Zelnik V & Scott SD. Construction and properties of a turkey herpesvirus recombinant expressing the Marek’s disease virus homologue of glycoprotein b of herpes simplex virus. J. Gen. Virol., 74:371-377. (1993).
  • Scott SD, Ross NJL & BinnsMM. Identification and sequence analysis of the homologues of the herpes simplex virus glycoprotein H in Marek’s disease virus and the herpesvirus of turkeys. J. Gen. Virol. 74:1185-1190. (1993).
  • Efstathiou S, Ho YM, Scott SD, Styles CJ & Gompels UA. Murine herpesvirus 68 is genetically related to the gammaherpesviruses Epstein-Barr virus and herpesvirus saimiri. J. Gen. Virol., 71:1365-1372. (1990).
  • Ross LJN, Sanderson MJ, Scott SD, Binns MM, Doel T & Milne B. Nucleotide sequence and characterisation of the Marek’s disease homologue of glycoprotein B (gB) of herpes simplex virus. J. Gen. Virol., 70:1789-1804. (1989).
  • Scott SD, Ross LJN & Binns MM. Nucleotide and predicted amino acid sequences of the Marek’s disease virus and turkey herpesvirus thymidine kinase genes; Comparison with thymidine kinase genes of other herpesviruses. J. Gen. Virol., 70:3055-3065. (1989).
  • Buckmaster AE, Scott SD, Boursnell MEG, Ross LJN & Binns MM. Gene sequence and mapping data from Marek’s disease virus and herpesvirus of turkeys: Implications for herpesvirus classification. J. Gen. Virol., 69:2033-2042. (1988).

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Last Updated 11/03/2016