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Dr Augustine Chen

Dr Augustine Chen

My current research focus involves the co-development of a transformative diagnostic test using Next-Generation Sequencing (NGS) with applications in medical, agriculture and environmental sensing sectors. This innovation has attracted pre-seed funding to undertake proof-of-concept experiments towards multimodal signal detection (genetic and epigenetic changes) in circulating tumour DNA. Through minor modification, this test could also be expanded to include other sample types in non-medical sectors and I am currently pursuing collaborations towards such applications.


My speciality has always centred around developing, using or combining existing and emerging methodologies to answer a variety of research questions. This included technical expertise utilising

Next Generation Sequencing, high-throughput imaging and drug screening assays, siRNA and miRNA delivery, mouse necropsy as well as standard molecular biology and cell culture techniques.
To date, I have undertaken a range of biomedical research, investigating various aspects of gene regulation in human diseases such as cancer and virus infection (HBV, HPV and norovirus). Such approaches have enabled the identification of disease states and targetable vulnerabilities and has led to the discovery of putative therapeutic drugs (which led to a provisional patent filing) and the development of a diagnostic test for a NZ company (which attracted joint funding from the Ministry of Science and Innovation Technology Transfer Voucher Scheme).

Growing up in Malaysia

Augustine grew up in Malaysia, he always liked biology and was just curious about things around him. His Dad was a nurse and became a trainer for medical assistants and then principal of a training school. Medical assistants were hugely valued in Malaysia due to the shortage of doctors. Based in a rural setting Augustine was able to visit his Dad at work and just look around. An ideal environment to spark an interest in biology.

Outside the lab Augustine likes fly fishing, socialising with family and friends, and gardening.

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Publications

Beetham, H., Chen, A., Telford, B. J., Single, A., Jarman, K. E., Lackovic, K., … Guilford, P. (2019). A high-throughput screen to identify novel synthetic lethal compounds for the treatment of E-cadherin-deficient cells. Scientific Reports, 9, 12511. doi: 10.1038/s41598-019-48929-0

Godwin, T. D., Kelly, S. T., Brew, T. P., Bougen-Zhukov, N. M., Single, A. B., Chen, A., Stylianou, C. E., … Currie, S. K., Telford, B. J., Beetham, H. G., … Black, M. A., & Guilford, P. J. (2019). E-cadherin-deficient cells have synthetic lethal vulnerabilities in plasma membrane organisation, dynamics and function. Gastric Cancer, 22(2), 273-286. doi: 10.1007/s10120-018-0859-1

Bougen-Zhukov, N., Nouri, Y., Godwin, T., Taylor, M., Hakkaart, C., Single, A., Brew, T., Permina, E., Chen, A., Black, M. A., & Guilford, P. (2019). Allosteric AKT inhibitors target synthetic lethal vulnerabilities in E-cadherin-deficient cells. Cancers, 11(9), 1359. doi: 10.3390/cancers11091359

Single, A., Chen, A., Telford, B., Beetham, H., & Guilford, P. (2017). Statins show synthetic lethality in E-cadherin-deficient cells and are synergistic with SRC and HDAC inhibitors. Clinical Cancer Research, 23(1, Suppl. ), B41. doi: 10.1158/1557-3265.PMCCAVULN16-B41

Guilford, P. J., Chen, A., Telford, B., Single, A., Beetham, H., & Godwin, T. (2017). Synthetic lethal targeting of E-cadherin-deficient cancers. Clinical Cancer Research, 23(1, Suppl.), B04. doi: 10.1158/1557-3265.PMCCAVULN16-B04

Journal - Research Article

Beetham, H., Chen, A., Telford, B. J., Single, A., Jarman, K. E., Lackovic, K., … Guilford, P. (2019). A high-throughput screen to identify novel synthetic lethal compounds for the treatment of E-cadherin-deficient cells. Scientific Reports, 9, 12511. doi: 10.1038/s41598-019-48929-0

Bougen-Zhukov, N., Nouri, Y., Godwin, T., Taylor, M., Hakkaart, C., Single, A., Brew, T., Permina, E., Chen, A., Black, M. A., & Guilford, P. (2019). Allosteric AKT inhibitors target synthetic lethal vulnerabilities in E-cadherin-deficient cells. Cancers, 11(9), 1359. doi: 10.3390/cancers11091359

Godwin, T. D., Kelly, S. T., Brew, T. P., Bougen-Zhukov, N. M., Single, A. B., Chen, A., Stylianou, C. E., … Currie, S. K., Telford, B. J., Beetham, H. G., … Black, M. A., & Guilford, P. J. (2019). E-cadherin-deficient cells have synthetic lethal vulnerabilities in plasma membrane organisation, dynamics and function. Gastric Cancer, 22(2), 273-286. doi: 10.1007/s10120-018-0859-1

Single, A., Beetham, H., Telford, B. J., Guilford, P., & Chen, A. (2015). A comparison of real-time and endpoint cell viability assays for improved synthetic lethal drug validation. Journal of Biomolecular Screening, 20(10), 1286-1293. doi: 10.1177/1087057115605765

Telford, B. J., Chen, A., Beetham, H., Frick, J., Brew, T. P., Gould, C. M., Single, A., Godwin, T., … Guilford, P. (2015). Synthetic lethal screens identify vulnerabilities in GPCR signalling and cytoskeletal organization in E-cadherin-deficient cells. Molecular Cancer Therapeutics, 14(5), 1213-1223. doi: 10.1158/1535-7163.mct-14-1092

Waugh, E., Chen, A., Baird, M. A., Brown, C. M., & Ward, V. K. (2014). Characterization of the chemokine response of RAW264.7 cells to infection by murine norovirus. Virus Research, 181, 27-34. doi: 10.1016/j.virusres.2013.12.025

Chen, A., T-Thienprasert, N. P., & Brown, C. M. (2014). Prospects for inhibiting the post-transcriptional regulation of gene expression in hepatitis B virus. World Journal of Gastroenterology, 20(25), 7993-8004. doi: 10.3748/wjg.v20.i25.7993

Chen, A., Beetham, H., Black, M. A., Priya, R., Telford, B. J., Guest, J., Wiggins, G. A. R., Godwin, T. D., … Guilford, P. J. (2014). E-cadherin loss alters cytoskeletal organization and adhesion in non-malignant breast cells but is insufficient to induce an epithelial-mesenchymal transition. BMC Cancer, 14, 552. doi: 10.1186/1471-2407-14-552

Chen, A., & Brown, C. (2012). Distinct families of cis-acting RNA replication epsilon elements from hepatitis B viruses. RNA Biology, 9(2), 130-136. doi: 10.4161/rna.18649

Jacobs, G. H., Chen, A., Stevens, S. G., Stockwell, P. A., Black, M. A., Tate, W. P., & Brown, C. M. (2009). Transterm: A database to aid the analysis of regulatory sequences in mRNAs. Nucleic Acids Research, 37(Database issue), D72-D76. doi: 10.1093/nar/gkn763

Chen, A., Kao, Y. F., & Brown, C. M. (2005). Translation of the first upstream ORF in the hepatitis B virus pregenomic RNA modulates translation at the core and polymerase initiation codons. Nucleic Acids Research, 33(4), 1169-1181.

Chen, A., Grigor, M. R., Thompson, C. M., & Harris, E. L. (1997). Kallikrein binding protein (KBP) maps to rat Chromosome 6 but does not cosegregate with blood pressure in a GH x BN cross. Mammalian Genome, 8(9), 701-703.

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Conference Contribution - Published proceedings: Abstract

Single, A., Chen, A., Telford, B., Beetham, H., & Guilford, P. (2017). Statins show synthetic lethality in E-cadherin-deficient cells and are synergistic with SRC and HDAC inhibitors. Clinical Cancer Research, 23(1, Suppl. ), B41. doi: 10.1158/1557-3265.PMCCAVULN16-B41

Guilford, P. J., Chen, A., Telford, B., Single, A., Beetham, H., & Godwin, T. (2017). Synthetic lethal targeting of E-cadherin-deficient cancers. Clinical Cancer Research, 23(1, Suppl.), B04. doi: 10.1158/1557-3265.PMCCAVULN16-B04

Chen, A., Telford, B. J., Single, A., Beetham, H., Simpson, K. J., & Guilford, P. J. (2016). Synthetic lethal approaches targeting E-cadherin-deficient cancers. Cancer Research, 76(14, Suppl.), 3814. doi: 10.1158/1538-7445.AM2016-3814

Beetham, H., Chen, A., Jarman, K. E., Falk, H., & Guilford, P. J. (2015). The discovery of novel synthetic lethal compounds for the treatment of E-cadherin deficient tumours. Proceedings of the Diagnostic Drug Device Discovery (D4) Conference. Retrieved from https://www.regonline.com.au/builder/site/Default.aspx?EventID=1758070

Chen, A., Telford, B., Beetham, H., Single, A., Godwin, T., & Guilford, P. (2013). Synthetic lethal interactions with the tumour suppressor protein E-cadherin. Proceedings of the New Zealand Society for Oncology (NZSO) Conference. Retrieved from http://www.nzsoncology.org.nz/conference_2013

Single, A., Chen, A., Telford, B., & Guilford, P. (2013). Synthetic lethal interactions for the treatment of E-cadherin negative tumours. New Zealand Medical Journal, 126(1374). Retrieved from http://www.nzma.org.nz/journal

Brown, C. M., Wilkinson, T., Panjaworayan, N., Firth, A. E., Chen, A., Stevens, S. G., Wong, A., Black, M., … Roessner, S. K. (2009). Analysis of virus and human genome sequences for RNA regulatory elements. Proceedings of the Webster Centre for Infectious Diseases Symposium. WCID. Retrieved from http://www.webstercentre.otago.ac.nz/WCIDSymposiumProgramme.pdf

Panjaworayan, N., Rackham, O., Chen, A., Kao, A. Y.-F., & Brown, C. M. (2005). Post-transcriptional regulation of gene expression in hepatitis B virus. Proceedings of the Meeting on the Molecular Biology of Hepatitis B Viruses. (pp. 30). Heidelberg, Germany. [Abstract]

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Conference Contribution - Poster Presentation (not in published proceedings)

Beetham, H., Chen, A., Single, A., Telford, B., & Guilford, P. (2015, October). The discovery of novel synthetic lethal compounds for the treatment of E-cadherin deficient tumours. Poster session presented at the Otago Spotlight Series: Cancer Research, Wellington, New Zealand.

Beetham, H., Chen, A., Single, A., Telford, B. J., & Guilford, P. J. (2015, August-September). The discovery of novel synthetic lethal compounds for the treatment of E-cadherin deficient tumours. Poster session presented at the Queenstown Molecular Biology (QMB) Meetings, Queenstown, New Zealand.

Single, A., Chen, A., & Guilford, P. (2015, October). A synergistic synthetic lethal drug combination for the treatment of E-cadherin-deficient tumours. Poster session presented at the Otago Spotlight Series: Cancer Research, Wellington, New Zealand.

Beetham, H., Chen, A., Telford, B. J., & Guilford, P. J. (2014, August). A cell based high throughput screen to find novel synthetic lethal lead-like compounds for the treatment of E-cadherin deficient tumours. Poster session presented at the Queenstown Molecular Biology (QMB) Meetings, Queenstown, New Zealand.

Chen, A., Sarman, A., Riad, S., Stevens, S., & Brown, C. (2011, September). Changes in gene expression in a breast cancer cell line using RNA-Seq. Poster session presented at the Queenstown Molecular Biology (QMB) Meetings, Queenstown, New Zealand.

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Conference Contribution - Verbal presentation and other Conference outputs

Kelly, S. T., Stylianou, C., Chen, A., Guilford, P. J., & Black, M. A. (2017, September). In silico detection of candidate synthetic lethal gene pairs using cancer genomics data. Verbal presentation at the Queenstown Molecular Biology (QMB) Meetings, Queenstown, New Zealand.

Guilford, P., Chen, A., Single, A., Beetham, H., Telford, B., Hakkaart, C., & Godwin, T. (2016, August-September). Hereditary diffuse gastric cancer: Battling the curse. Verbal presentation at the Queenstown Molecular Biology (QMB) Meetings, Nelson, New Zealand.

Guilford, P., Telford, B., Chen, A., Beetham, H., Single, A., Frick, J., Brew, T., & Godwin, T. (2014, November). Synthetic lethal targeting of E-cadherin-deficient cancers. Verbal presentation at the Frontiers of Biology Satellite Meeting: From Protein Structure and Function to Drugs, Wellington, New Zealand.

Garama, D., Stevens, S., Chen, X., Biswas, A., Sarman, A., Chen, A., & Brown, C. (2013, February). Translational control of gene expression by mRNA elements. Verbal presentation at the 38th Lorne Conference on Protein Structure and Function, Lorne, Australia.

Guilford, P., Telford, B., Black, M., & Chen, A. (2012, August). Synthetic lethal targeting of the tumour suppressor gene CDH1 in common cancers. Invited presentation at the Queenstown Molecular Biology (QMB) Meetings, Queenstown, New Zealand.

Stevens, S. G., Biswas, A., Gagnon, J., Wilkinson, T., Chen, A., Chen, S., & Brown, C. M. (2011, August). Bioinformatic approaches to the identification of localisation elements. Verbal presentation at the European Molecular Biology Organization (EMBO) Conference on Intracellular RNA Localization & Localized Translation, Tuscany, Italy.

Brown, C. M., Das, A., Stevens, S., Biswas, A., Gagnon, J., McKinney, C., Chen, A., & Chen, S. (2011, September). Bioinformatic approaches to discover post-transcriptional regulatory elements in human mRNAs. Verbal presentation at the Queenstown Molecular Biology (QMB) Meetings, Queenstown, New Zealand.

Brown, C., Chen, A., Ballantine, S., Black, M., Jacobs, G., & Stevens, S. (2008, November-December). Identification of post-transcriptional regulatory elements in mRNA sequences. Verbal presentation at the New Zealand Institute of Chemistry, New Zealand Society for Biochemistry and Molecular Biology and the New Zealand Society of Plant Biologists Combined Conference, Dunedin, New Zealand.

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Awarded Doctoral Degree

Chen, A. (2007). Translational control mechanisms used by the human Hepatitis B virus: An upstream open reading frame modulates expression of the pregenomic RNA (PhD). University of Otago, Dunedin, New Zealand. 155p.

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