Background
Associate Professor Gabi Dachs completed her undergraduate and PhD studies in Cape Town, South Africa, followed by postdoctoral work at the MRC Harwell in the United Kingdom.
Prior to joining the University of Otago in Christchurch, Associate Professor Dachs worked as senior scientist at the Gray Cancer Institute in London, UK.
Research interests
Associate Professor Gabi Dachs is interested in why human tumours are difficult to treat, and in new ways of treating them.
Current research interests at present include:
- Can we dampen the activity of the global transcription factor HIF-1 using vitamin C? Can we reduce tumour growth in mice using vitamin C? Can we increase vitamin C in cancer cells using gene therapy? What is the relationship between ascorbate and HIF-1 in tumours from kidney cancer patients?
- Why do obese cancer patients often fare worse than non-obese patients? Can we identify the molecular factors associated with obesity in cancer? What effect do these obesity-related factors have on chemotherapy?
- Which human enzymes are responsible for the activation of novel anticancer prodrugs (in collaboration with Auckland Cancer Society Research Centre)? Can this knowledge guide clinical use of these agents?
- Can we improve gene directed enzyme prodrug therapy combinations to target solid tumours or their vasculature?
In the media
Associate Professor Gabi Dachs was featured in Radio New Zealand's The Science Of... Vitamin C in August 2017.
Publications
Buss, L. A., & Dachs, G. U. (2020). Effects of exercise on the tumour microenvironment. In A. Birbrair (Ed.), Tumor microenvironment: Recent advances. (pp. 31-51). Cham, Switzerland: Springer. doi: 10.1007/978-3-030-35727-6_3
White, R., Nonis, M., Pearson, J. F., Burgess, E., Morrin, H. R., Pullar, J. M., Spencer, E., Vissers, M. C. M., Robinson, B. A., & Dachs, G. U. (2020). Low vitamin C status in patients with cancer is associated with patient and tumor characteristics. Nutrients, 12(8), 2338. doi: 10.3390/nu12082338
Buss, L. A., Ang, A. D., Hock, B., Robinson, B. A., Currie, M. J., & Dachs, G. U. (2020). Effect of post-implant exercise on tumour growth rate, perfusion and hypoxia in mice. PLoS ONE, 15(3), e0229290. doi: 10.1371/journal.pone.0229290
Pullar, J. M., Dunham, S., Dachs, G. U., Vissers, M. C. M., & Carr, A. C. (2020). Erythrocyte ascorbate is a potential indicator of steady-state plasma ascorbate concentrations in healthy non-fasting individuals. Nutrients, 12(2), 418. doi: 10.3390/nu12020418
Wohlrab, C., Kuiper, C., Vissers, M. C. M., Phillips, E., Robinson, B. A., & Dachs, G. U. (2019). Ascorbate modulates the hypoxic pathway by increasing intracellular activity of the HIF hydroxylases in renal cell carcinoma cells. Hypoxia, 7, 17-31. doi: 10.2147/hp.S201643
Chapter in Book - Research
Buss, L. A., & Dachs, G. U. (2020). Effects of exercise on the tumour microenvironment. In A. Birbrair (Ed.), Tumor microenvironment: Recent advances. (pp. 31-51). Cham, Switzerland: Springer. doi: 10.1007/978-3-030-35727-6_3
Journal - Research Article
White, R., Nonis, M., Pearson, J. F., Burgess, E., Morrin, H. R., Pullar, J. M., Spencer, E., Vissers, M. C. M., Robinson, B. A., & Dachs, G. U. (2020). Low vitamin C status in patients with cancer is associated with patient and tumor characteristics. Nutrients, 12(8), 2338. doi: 10.3390/nu12082338
Pullar, J. M., Dunham, S., Dachs, G. U., Vissers, M. C. M., & Carr, A. C. (2020). Erythrocyte ascorbate is a potential indicator of steady-state plasma ascorbate concentrations in healthy non-fasting individuals. Nutrients, 12(2), 418. doi: 10.3390/nu12020418
Buss, L. A., Ang, A. D., Hock, B., Robinson, B. A., Currie, M. J., & Dachs, G. U. (2020). Effect of post-implant exercise on tumour growth rate, perfusion and hypoxia in mice. PLoS ONE, 15(3), e0229290. doi: 10.1371/journal.pone.0229290
Wohlrab, C., Kuiper, C., Vissers, M. C. M., Phillips, E., Robinson, B. A., & Dachs, G. U. (2019). Ascorbate modulates the hypoxic pathway by increasing intracellular activity of the HIF hydroxylases in renal cell carcinoma cells. Hypoxia, 7, 17-31. doi: 10.2147/hp.S201643
Campbell, E. J., Dachs, G. U., Morrin, H. R., Davey, V., Robinson, B. A., & Vissers, M. C. M. (2019). Activation of the hypoxia pathway in breast cancer tissue and patient survival are inversely associated with tumor ascorbate levels. BMC Cancer, 19, 307. doi: 10.1186/s12885-019-5503-x
Wohlrab, C., Vissers, M. C. M., Phillips, E., Morrin, H., Robinson, B. A., & Dachs, G. U. (2018). The association between ascorbate and the hypoxia-inducible factors in human renal cell carcinoma requires a functional von Hippel-Lindau protein. Frontiers in Oncology, 8, 574. doi: 10.3389/fonc.2018.00574
Buss, L. A., Mandani, A., Phillips, E., Scott, N. J. A., Currie, M. J., & Dachs, G. U. (2018). Characterisation of a mouse model of breast cancer with metabolic syndrome. In Vivo, 32(5), 1071-1080. doi: 10.21873/invivo.11348
Buss, L. A., & Dachs, G. U. (2018). The role of exercise and hyperlipidaemia in breast cancer progression. Exercise Immunology Review, 24, 8-23.
Buss, L. A., & Dachs, G. U. (2018). Voluntary exercise slows breast tumor establishment and reduces tumor hypoxia in ApoE-/- mice. Journal of Applied Physiology, 124(4), 938-949. doi: 10.1152/japplphysiol.00738.2017
Robinson, B., Currie, M., Phillips, E., Dachs, G., Strother, M., Morrin, H., Davey, V., & Frampton, C. (2017). Body mass index (BMI): Association with clinicopathological factors and outcome of women with newly diagnosed breast cancer in New Zealand. New Zealand Medical Journal, 130(1451), 46-56. Retrieved from https://www.nzma.org.nz/journal
Wohlrab, C., Phillips, E., & Dachs, G. U. (2017). Vitamin C transporters in cancer: Current understanding and gaps in knowledge. Frontiers in Oncology, 7, 74. doi: 10.3389/fonc.2017.00074
Bonifert, G., Folkes, L., Gmeiner, C., Dachs, G., & Spadiut, O. (2016). Recombinant horseradish peroxidase variants for targeted cancer treatment. Cancer Medicine, 5(6), 1194-1203. doi: 10.1002/cam4.668
Campbell, E. J., Vissers, M. C. M., & Dachs, G. U. (2016). Ascorbate availability affects tumor implantation-take rate and increases tumor rejection in Gulo-/- mice. Hypoxia, 4, 41-52. doi: 10.2147/HP.S103088
Campbell, E. J., Vissers, M. C. M., Wohlrab, C., Hicks, K. O., Strother, R. M., Bozonet, S. M., Robinson, B. A., & Dachs, G. U. (2016). Pharmacokinetic and anti-cancer properties of high dose ascorbate in solid tumours of ascorbate-dependent mice. Free Radical Biology & Medicine, 99, 451-462. doi: 10.1016/j.freeradbiomed.2016.08.027
Campbell, E. J., Vissers, M. C. M., Bozonet, S., Dyer, A., Robinson, B. A., & Dachs, G. U. (2015). Restoring physiological levels of ascorbate slows tumor growth and moderates HIF-1 pathway activity in Gulo−/− mice. Cancer Medicine, 4(2), 303-314. doi: 10.1002/cam4.349
Dachs, G. U., Phillips, E., Phung, Y., Dyer, A., Willis, J. A., Currie, M. J., & Robinson, B. A. (2015). Tumour growth in mice resistant to diet-induced obesity. Journal of Molecular Biochemistry, 4(2), 42-49.
Campbell, E. J., & Dachs, G. U. (2014). Current limitations of murine models in oncology for ascorbate research. Frontiers in Oncology, 4, 282. doi: 10.3389/fonc.2014.00282
Volkova, E., Robinson, B. A., Willis, J., Currie, M. J., & Dachs, G. U. (2014). Marginal effects of glucose, insulin and insulin-like growth factor on chemotherapy response in endothelial and colorectal cancer cells. Oncology Letters, 7(2), 311-320. doi: 10.3892/ol.2013.1710
Flett, T., Campbell, E. J., Phillips, E., Vissers, M. C. M., & Dachs, G. U. (2014). Gulonolactone addition to human hepatocellular carcinoma cells with gene transfer of gulonolactone oxidase restores ascorbate biosynthesis and reduces hypoxia inducible factor 1. Biomedicines, 2(1), 98-109. doi: 10.3390/biomedicines2010098
Vissers, M. C. M., Kuiper, C., & Dachs, G. U. (2014). Regulation of the 2-oxoglutarate-dependent dioxygenases and implications for cancer. Biochemical Society Transactions, 42(4), 945-951. doi: 10.1042/bst20140118
Kanthou, C., Dachs, G. U., Lefley, D. V., Steele, A. J., Coralli-Foxon, C., Harris, S., … Tozer, G. M. (2014). Tumour cells expressing single VEGF isoforms display distinct growth, survival and migration characteristics. PLoS ONE, 9(8), e104015. doi: 10.1371/journal.pone.0104015
Kuiper, C., Dachs, G. U., Currie, M. J., & Vissers, M. C. M. (2014). Intracellular ascorbate enhances hypoxia-inducible factor (HIF)-hydroxylase activity and preferentially suppresses the HIF-1 transcriptional response. Free Radical Biology & Medicine, 69, 308-317. doi: 10.1016/j.freeradbiomed.2014.01.033
Wang, J., Guise, C. P., Dachs, G. U., Phung, Y., Hsu, A. H.-L., Lambie, N. K., … Wilson, W. R. (2014). Identification of one-electron reductases that activate both the hypoxia prodrug SN30000 and diagnostic probe EF5. Biochemical Pharmacology, 91(4), 436-446. doi: 10.1016/j.bcp.2014.08.003
Kuiper, C., Dachs, G. U., Munn, D., Currie, M. J., Robinson, B. A., Pearson, J. F., & Vissers, M. C. M. (2014). Increased tumour ascorbate is associated with extended disease-free survival and decreased hypoxia-inducible factor-1 activation in human colorectal cancer. Frontiers in Oncology, 4, 10. doi: 10.3389/fonc.2014.00010
Currie, M. J., Beardsley, B. E., Harris, G. C., Gunningham, S. P., Dachs, G. U., Dijkstra, B., Morrin, H. R., Wells, J. E., & Robinson, B. A. (2013). Immunohistochemical analysis of cancer stem cell markers in invasive breast carcinoma and associated ductal carcinoma in situ: Relationships with markers of tumor hypoxia and microvascularity. Human Pathology, 44(3), 402-411. doi: 10.1016/j.humpath.2012.06.004
Hunt, M. A., Li, D., Hay, M. P., Currie, M. J., Robinson, B. A., Patterson, A. V., & Dachs, G. U. (2012). Characterisation of enzyme prodrug gene therapy combinations in coated spheroids and vascular networks in vitro. Journal of Gene Medicine, 14(1), 62-74. doi: 10.1002/jgm.1635
Guise, C. P., Abbattista, M. R., Tipparaju, S. R., Lambie, N. K., Su, J., Li, D., … Dachs, G. U., & Patterson, A. V. (2012). Diflavin oxidoreductases activate the bioreductive prodrug PR-104A under hypoxia. Molecular Pharmacology, 81(1), 31-40. doi: 10.1124/mol.111.073759
Volkova, E., Willis, J. A., Wells, J. E., Robinson, B. A., Dachs, G. U., & Currie, M. J. (2011). Association of angiopoietin-2, C-reactive protein and markers of obesity and insulin resistance with survival outcome in colorectal cancer. British Journal of Cancer, 104, 51-59. doi: 10.1038/sj.bjc.6606005
MacKenzie, K. A., Miller, A. P., Hock, B. D., Gardner, J., Simcock, J. W., Roake, J. A., Dachs, G. U., Robinson, B. A., & Currie, M. J. (2011). Angiogenesis and host immune response contribute to the aggressive character of non-melanoma skin cancers in renal transplant recipients. Histopathology, 58(6), 875-885. doi: 10.1111/j.1365-2559.2011.03845.x
Kuiper, C., Molenaar, I. G. M., Dachs, G. U., Currie, M. J., Sykes, P. H., & Vissers, M. C. M. (2010). Low ascorbate levels are associated with increased hypoxia-inducible factor-1 activity and an aggressive tumor phenotype in endometrial cancer. Cancer Research, 70(14), 5749-5758. doi: 10.1158/0008-5472.CAN-10-0263
Hunt, M. A., Currie, M. J., Robinson, B. A., & Dachs, G. U. (2010). Optimizing transfection of primary human umbilical vein endothelial cells using commercially available chemical transfection reagents. Journal of Biomolecular Techniques, 21, 66-72.
Guise, C. P., Abbattista, M. R., Singleton, R. S., Holford, S. D., Connolly, J., Dachs, G. U., Fox, S. B., Pollock, R., Harvey, J., Guilford, P., … Patterson, A. V. (2010). The bioreductive prodrug PR-104A is activated under aerobic conditions by human aldo-keto reductase 1C3. Cancer Research, 70(4), 1573-1584. doi: 10.1158/0008-5472.CAN-09-3237
Dachs, G. U., Kano, M., Volkova, E., Morrin, H. R., Davey, V. C. L., Harris, G. C., … Frampton, C., Currie, M. J., Wells, J. E., & Robinson, B. A. (2010). A profile of prognostic and molecular factors in European and Māori breast cancer patients. BMC Cancer, 10, 543. doi: 10.1186/1471-2407-10-543
Tupper, J., Stratford, M. R., Hill, S., Tozer, G. M., & Dachs, G. U. (2010). In vivo characterization of horseradish peroxidase with indole-3-acetic acid and 5-bromoindole-3-acetic acid for gene therapy of cancer. Cancer Gene Therapy, 17(6), 420-428. doi: 10.1038/cgt.2009.86
Dachs, G. U., Hunt, M. A., Syddall, S., Singleton, D. C., & Patterson, A. V. (2009). Bystander or no bystander for gene directed enzyme prodrug therapy. Molecules, 14(11), 4517-4545. doi: 10.3390/molecules14114517
Dachs, G. U., Currie, M. J., Mckenzie, F., Jeffreys, M., Cox, B., Foliaki, S., … Robinson, B. A. (2008). Cancer disparities in indigenous Polynesian populations: Māori, Native Hawaiians, and Pacific people. Lancet Oncology, 9(5), 473-484. doi: 10.1016/S1470-2045(08)70127-X
Vissers, M. C. M., Gunningham, S. P., Morrison, M. J., Dachs, G. U., & Currie, M. J. (2007). Modulation of hypoxia-inducible factor-1 alpha in cultured primary cells by intracellular ascorbate. Free Radical Biology & Medicine, 42, 765-772.
Gunningham, S. P., Currie, M. J., Morrin, H. R., Tan, E. Y., Turley, H., Dachs, G. U., Watson, A. I., Frampton, C., Robinson, B. A., & Fox, S. B. (2007). The angiogenic factor thymidine phosphorylase up-regulates the cell adhesion molecule P-selectin in human vascular endothelial cells and is asociated with P-selectin expression in breast cancers. Journal of Pathology, 212, 335-344.
Dachs, G. U., Steele, A. J., Coralli, C., Kanthou, C., Brooks, A. C., Gunningham, S. P., Currie, M. J., Watson, A. I., Robinson, B. A., & Tozer, G. M. (2006). Anti-vascular agent Combretastatin A-4-P modulates hypoxia inducible factor-I and gene expression. BMC Cancer, 6, 280. doi: 10.1186/1471-2407-6-280
Morrin, H., Gunningham, S., Currie, M., Dachs, G., Fox, S., & Robinson, B. (2005). The Christchurch Tissue Bank to support cancer research. New Zealand Medical Journal, 118(1225). Retrieved from http://journal.nzma.org.nz/journal/118-1225/1735/content.pdf
Dachs, G. U., Tupper, J., & Tozer, G. M. (2005). From bench to bedside for gene-directed enzyme prodrug therapy of cancer. Anti-Cancer Drugs, 16, 349-359.
Williams, K. J., Telfer, B. A., Xenaki, D., Sheridan, M. R., Desbaillets, I., Peters, H. J. W., … Dachs, G. U., … Stratford, I. J. (2005). Enhanced response to radiotherapy in tumours deficient in the function of hypoxia-inducible factor-1. Radiotherapy & Oncology, 75, 89-98. doi: 10.1016/j.radonc.2005.01.009
Tupper, J., Greco, O., Tozer, G. M., & Dachs, G. U. (2004). Analysis of the horseradish peroxidase/indole-3-acetic acid combination in a three-dimensional tumor model. Cancer Gene Therapy, 11(7), 508-513.
Cemazar, M., Wilson, I., Dachs, G. U., Tozer, G. M., & Sersa, G. (2004). Direct visualization of electroporation-assisted in vivo gene delivery to tumors using intravital microscopy: Spatial and time dependent distribution. BMC Cancer, 4(81). Retrieved from http://www.biomedcentral.com/1471-2407/4/81
Tupper, J., Tozer, G. M., & Dachs, G. U. (2004). Use of horseradish peroxidase for gene-directed enzyme prodrug therapy with paracetamol. British Journal of Cancer, 90(9), 1858-1862.
Dachs, G. U., Greco, O., & Tozer, G. M. (2004). Targeting cancer with gene therapy using hypoxia as a stimulus. Methods in Molecular Medicine, 90, 371-387.
Greco, O., Marples, B., Dachs, G., Williams, K. J., Patterson, A. V., Scott, S. D., & Hsieh, J. T. (2003). Novel chimeric gene promoters responsive to hypoxia and ionizing radiation. Urologic Oncology, 21(4), 314.
Greco, O., Tozer, G. M., & Dachs, G. U. (2002). Oxic and anoxic enhancement of radiation-mediated toxicity by horseradish peroxidase/indole-3-acetic acid gene therapy. International Journal of Radiation Biology, 78(3), 173-181.
Greco, O., Marples, B., Dachs, G. U., Williams, K. J., Patterson, A. V., & Scott, S. D. (2002). Novel chimeric gene promoters responsive to hypoxia and ionizing radiation. Human Gene Therapy, 9, 1403-1411.
Tumor cell proliferation
Tumor vascularity
Tumor hypoxia
