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 and cancer biology 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, and will be supervising a 4th year research project student and a PhD student from October 2007.

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Simon’s research is focussed on developing gene therapy vector systems for the treatment of solid tumours. These DNA-based 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, is 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/lox) 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. Theses include 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.

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• 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.
• 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.
• 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, Joiner MC & Marples B (2002). Optimizing radiation-responsive gene promoters for radiogenetic cancer therapy. Gene Therapy 9: 1396-1402.
• 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.
• Greco O, Powell T, Joiner MC, Marples B & Scott SD (2005). Synthetic promoters containing CArG elements from the Egr-1 gene are activated by neutron irradiation, cisplatin and doxorubicin. Cancer Gene Therapy 12: 655-662.
• 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.
• 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, 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.
• Greco O & Scott S (2007). Tumor Hypoxia and Targeted Gene Therapy. International Review of Cytology 257: 181-212

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