Dr Alexandra Mowday
BSc, MSc, PhD
Postdoctoral research fellow at the Auckland Cancer Society Research Centre and member of the Translational Therapeutics Team led by Associate Professor Adam Patterson.
Research | Current
Tumour necrosis is a typical histological feature of solid cancers that is associated with high-risk tumour characteristics and poor patient survival. Currently no therapeutic modality exists to address this clinical problem, yet necrosis offers the most desirable of all attributes for targeted therapy – absolute specificity for neoplasia (being categorically absent in normal healthy tissues). Live biotherapeutics employing bacterial vectors is a rapidly advancing area of experimental oncology and has been described as ‘the perfect cancer therapy’. Of the available platforms, the strict anaerobic bacteria Clostridum sporogenes exhibits an overt preference for necrotic tissues and is the most intrinsically selective for solid tumours. The germination of endospores is restricted to anaerobic environments whilst the vegetative bacteria are killed by direct exposure to oxygen. This offers a unique opportunity to turn a pathological feature associated with treatment failure into a precision therapy.
Low inherent anti-tumour activity of C. sporogenes necessitates development of ‘armed’ vectors; an approach termed Clostridium Directed Enzyme Prodrug Therapy (CDEPT). However to date progress has been hampered by challenges associated with stable genetic modification of the bacterial genome. This limitation has recently been overcome, allowing (for the first time) the opportunity for development of clinical grade endospore preparations compatible with medical authority regulatory requirements. As part of an international multidisciplinary collaboration, we have isolated a library of metabolically flexible bacterial nitroreductase (NTR) genes able to perform multiple functions via a single gene product; metabolism of NTR-specific PET imaging agents (for whole body vector visualisation) as well as preclinical chemotherapy prodrugs (for conditional enhancement of efficacy). We now seek to develop an NTR-armed C. sporogenes therapeutic product suitable for advancement to clinical testing.
Current research is supported by a Health Research Council of New Zealand project grant titled ‘Colonising tumour necrosis with Clostridium sporogenes for precision therapy’.
2014: Brett Roche Memorial Award, Auckland Cancer Society
2011: Doctoral Scholarship, University of Auckland
2009: Faculty of Science Masters award, University of Auckland
Areas of expertise
- Cancer gene therapy (GDEPT, CDEPT)
- Clostridium sporogenes
- Oncolytic viruses
- Tumour necrosis
- Cancer drug development
- Nitrogen mustard prodrugs
- Bacterial nitroreductases
- Gene therapy imaging modalities
2014-Present: Affiliate Investigator, Maurice Wilkins Centre for Molecular Biodiscovery
Selected publications and creative works (Research Outputs)
- Copp, J. N., Mowday, A. M., Williams, E. M., Guise, C. P., Ashoorzadeh, A., Sharrock, A. V., ... Ackerley, D. F. (2017). Engineering a Multifunctional Nitroreductase for Improved Activation of Prodrugs and PET Probes for Cancer Gene Therapy. Cell chemical biology, 24 (3), 391-403. 10.1016/j.chembiol.2017.02.005
Other University of Auckland co-authors: Jeffrey Smaill, Christopher Guise, Amir Ashoorzadeh, Jack Flanagan, Adam Patterson
- Mowday, A. M., Ashoorzadeh, A., Williams, E. M., Copp, J. N., Silva, S., Bull, M. R., ... Guise, C. P. (2016). Rational design of an AKR1C3-resistant analog of PR-104 for enzyme-prodrug therapy. Biochemical Pharmacology, 116, 176-187. 10.1016/j.bcp.2016.07.015
Other University of Auckland co-authors: Jack Flanagan, Adam Patterson, Bob Anderson, Jeffrey Smaill, Christopher Guise, Maria Abbattista, Amir Ashoorzadeh, Matthew Bull
- Mowday, A. M., Guise, C. P., Ackerley, D. F., Minton, N. P., Lambin, P., Dubois, L. J., ... Patterson, A. V. (2016). Advancing Clostridia to Clinical Trial: Past Lessons and Recent Progress. Cancers, 8 (7), 1-14. 10.3390/cancers8070063
Other University of Auckland co-authors: Adam Patterson, Jeffrey Smaill, Christopher Guise
- Williams, E. M., Little, R. F., Mowday, A. M., Rich, M. H., Chan-Hyams, J. V. E., Copp, J. N., ... Ackerley, D. F. (2015). Nitroreductase gene-directed enzyme prodrug therapy: insights and advances toward clinical utility. The Biochemical journal, 471 (2), 131-153. 10.1042/bj20150650
Other University of Auckland co-authors: Adam Patterson, Jeffrey Smaill
- Mowday, A. M. (2015). Discovery and development of imaging-capable bacterial nitroreductases and their cytotoxic prodrugs for Clostridium sporogenes based gene therapy The University of Auckland. ResearchSpace@Auckland.
- Guise, C. P., Mowday, A. M., Ashoorzadeh, A., Yuan, R., Lin, W.-H., Wu, D.-H., ... Ding, K. (2014). Bioreductive prodrugs as cancer therapeutics: targeting tumor hypoxia. Chinese journal of cancer, 33 (2), 80-86. 10.5732/cjc.012.10285
Other University of Auckland co-authors: Adam Patterson, Christopher Guise, Jeffrey Smaill, Amir Ashoorzadeh
- Prosser, G. A., Copp, J. N., Mowday, A. M., Guise, C. P., Syddall, S. P., Williams, E. M., ... Denny, W. A. (2013). Creation and screening of a multi-family bacterial oxidoreductase library to discover novel nitroreductases that efficiently activate the bioreductive prodrugs CB1954 and PR-104A. Biochemical pharmacology, 85 (8), 1091-1103. 10.1016/j.bcp.2013.01.029
Other University of Auckland co-authors: Christopher Guise, Jeffrey Smaill, Bill Denny, Amir Ashoorzadeh, Adam Patterson
- Green, L. K., Syddall, S. P., Carlin, K. M., Bell, G. D., Guise, C. P., Mowday, A. M., ... Ackerley, D. F. (2013). Pseudomonas aeruginosa NfsB and nitro-CBI-DEI--a promising enzyme/prodrug combination for gene directed enzyme prodrug therapy. Molecular cancer, 1210.1186/1476-4598-12-58
Other University of Auckland co-authors: Christopher Guise, Jeffrey Smaill, Michael Hay, Adam Patterson, Glenn Bell