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 and Foundation courses at the School, both in the classroom and laboratory. He was directly involved in the design and setup of the new biological sciences laboratories at MSoP, and annually supervises a number of 4th year research project students in the labs. He also supervised a successful MSc student on a gene therapy/molecular biology 3 year research project.

Simon currently has a new PhD position available to start late 2011, co-supervised with Dr Nigel Temperton, working on influenza pseudotype viruses.

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Simon’s research is focussed on developing 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 virus ‘pseudotypes’ to study influenza, 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. Consequently, 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, recently awarded funding by the British Heart Foundation, will involve 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.

Lastly, work in the new VPU will involve the production of non-pathogenic ‘pseudotype’ lentiviruses bearing the haemagglutinin and neuraminidase surface proteins from influenza virus. These will be used in serological studies to monitor new influenza outbreaks worldwide, identify antiviral ‘escape’ mutants and provide information which may be useful in future seasonal and pandemic influenza vaccine development.

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

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• 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 & Scott S (2007). Tumor Hypoxia and Targeted Gene Therapy. International Review of Cytology 257: 181-212
• 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.
• 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.
• 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.
• 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.

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