Principal Investigator
Associate Dean (Postgraduate Studies)
MSc(Hons)(Cant), PhD(Auck)
Email margaret.currie@otago.ac.nz
Tel +64 3 364 0544
Research interests
Associate Professor Margaret Currie is interested in how the tumour microenvironment affects tumour growth, tumour cell metastasis and tumour response to therapy.
The local tumour microenvironment is the milieu within which the tumour develops, and includes tumour blood vessels, other cells types (e.g. immune cells, fibroblasts, adipocytes), soluble growth factors and signalling molecules. All the various components of the tumour microenvironment can influence tumour growth and spread and, conversely, tumour cells can influence the local tumour microenvironment.
A further layer of complexity exists because the wider tumour microenvironment (i.e. the body within which the tumour develops) alters with age and health, and is affected by systemic changes in metabolism, hormones and immunity.
The Mackenzie Cancer Research Group has been investigating the contribution of stromal cells and the tumour microenvironment to human tumour biology since the inception of our research group in 1998. Initially, their research focused on tumour blood vessel development and anti-angiogenic therapies. However, since 2009 Associate Professor Currie's interests have expanded to include the contribution to tumour progression made by tumour infiltrating immune cell populations, breast cancer stem cell-like populations, and obesity-related factors.
Current projects
Adipocytes in tumour stroma
In various human cancers, obesity is linked to invasive tumours that are resistant to therapy and have poor outcome. We are culturing human fat cells (adipocytes) and tumour cells together, to find out how adipocytes alter tumour cell phenotype and response to therapy. We are also studying tumour samples from normal weight and obese breast cancer patients to better understand the role adipocytes play in promoting aggressive tumour growth and spread, and identify patients likely to benefit from additional treatment during cancer therapy.
Circulating immune cell populations and tumour infiltrating immune cells in human cancers
Cutaneous squamous cell carcinomas (cSCC) are common in NZ, and most are simply treated. However, a small proportion (~5%) of these skin cancers grow aggressively, spread to other organs, and cause death. In patients who have had an organ transplant, we have identified blood vessel and immune characteristics that are correlated to cSCC aggressiveness. We are currently investigating whether these characteristics also account for the aggressiveness of cSCCs in non-transplant patients. A greater understanding of the biology of these tumours may help clinicians identify at-risk patients who could benefit from additional treatment and close surveillance. In addition, the specific immune and blood vessel factors identified are potential targets for developing novel cancer treatments.
Postgraduate supervision
Student: Linda Buss
Degree: PhD (in progress)
Thesis title: Investigating exercise-mediated changes in the tumour microenvironment of melanoma and lung cancer
Supervisors: G Dachs, M Currie, B Hock, B Robinson
Student: Ifran Yunianto
Degree: PhD (in progress)
Thesis title: The role of inflammation in ovarian cancer
Supervisors: P Sykes, K Chitcholtan, M Currie
Student: Rebekah Crake
Degree: PhD (in progress)
Thesis title: The local and systemic affects of inflammatory adipokines on mechanisms of resistance to chemotherapy in obese breast cancer patients
Supervisors: M Currie, E Phillips, M Strother, B Robinson
Student: Mohini Puri
Degree: MMedSc (in progress)
Thesis title: Adipocytes and collagen in breast tumours
Supervisors: M Currie, E Phillips
Student: Annika Seddon
Degree: PhD (in progress)
Thesis title: Investigating the biology of tumour-associated neutrophils
Supervisors: M Hampton, M Currie, A Kettle
Student: Arthur Morley-Bunker
Degree: PhD (in progress)
Thesis title: Scoping for RNA biomarkers for colorectal cancer
Supervisors: L Walker, J Pearson, M Currie, T Eglington
2017
Student: Dr Vanessa Lattimore
Degree: PhD
Thesis title: Evaluating BRCA1 and BRCA2 sequence variants that modulate isoform expression
Supervisors: L Walker, M Currie, B Robinson
2015
Student: Dr Anthony Rahman
Degree: PhD
Thesis title: Venous Thromboembolism (VTE) in cancer patients commencing chemotherapy
Supervisors: B Robinson, M Smith, M Currie, S Gunningham
2013
Student: Caroline Kuiper
Degree: PhD
Thesis title: The role of ascorbate in the regulation of HIF-1 in cancer cells
Supervisors: M Vissers, G Dachs, M Currie
2011
Student: Ekaterina Volkova
Degree: PhD
Thesis title: Obesity and colorectal cancer
Supervisors: M Currie, G Dachs, J Willis, B Robinson
2010
Student: Michelle Hunt
Degree: PhD
Thesis title: Vessel directed enzyme prodrug therapy for cancer
Supervisors: G Dachs, M Currie, A Patterson, B Robinson
Student: Kasia Mackenzie
Degree: PhD
Thesis title: Why are skin cancers more aggressive in renal transplant recipients?
Supervisors: M Currie, B Hock, J Simcock, B Robinson, J Roake
2007
Student: Sarah Gunningham
Degree: PhD
Thesis title: The role of VEGF faminly in breast and colorectal cancer
Supervisors: M Currie, V Cameron, B Robinson, S Fox
Student: So Young Moon
Degree: PhD
Thesis title: Identification of genetic aberrations in chronic lymphocytic leukaemia using array CGH
Supervisors: C Morris, P Ganly, M Currie
2017
Student: Leah Butt
Degree: BBiomedSc(Hons)
Thesis title: Measuring markers of immune response in patients treated with Nivolumab (Opdivo) or Pembrolizumab (Keytruda)
Supervisors: M Currie, B Hock, M Strother
2015
Student: Morgan Jones
Degree: BBiomedSc(Hons)
Thesis title: Does fat provide energy for breast cancer cell invasion and metastasis?
Supervisors: M Currie, E Phillips
Student: Rebekah Crake
Degree: BBiomedSc(Hons)
Thesis title: Obesity and breast cancer development
Supervisors: L Walker, M Currie, E Phillips
Student: Anishah Mandani
Degree: BBiomedSc(Hons)
Thesis title: Development of a breast cancer ApoE/ArKO mouse model
Supervisors: G Dachs, M Currie
2013
Student: Annika Seddon
Degree: BBiomedSc(Hons)
Thesis title: Immune Suppression and Squamous Cell Carcinoma Tumour Biology
Supervisors: M Currie, B Hock
2010
Student: Anna Van Pomeren
Degree: BBiomedSc(Hons)
Thesis title: Myeloid-derived suppressor cells and tumour angiogenesis
Supervisors: M Currie, B Hock
2014
Student: Lisa Brennan
Degree: MSc (Massey University)
Thesis title: Biomarkers as predictors of six month survival outcomes of patients presenting with solid tumours
Supervisors: M Currie, A Rahman, B Robinson, C Kendrick
2007
Student:Maiko Kano
Degree: BMedSc
Thesis title: Biology of cancer in Maori
Supervisors: G Dachs, M Currie, B Robinson
Funding
- The Mackenzie Charitable Foundation
- Cancer Society of New Zealand (& CSNZ Canterbury-West Coast Division)
- University of Otago Christchurch Cancer Fellowship
- New Zealand Breast Cancer Foundation
- University of Otago
Selected Recent Publications
- Seddon AR, Hock BD, Miller AP, Frei LP, Pearson JF, McKenzie JL, Simcock JW, Currie MJ. Cutaneous squamous cell carcinomas with markers of increased metastatic risk are associated with elevated numbers of neutrophils and/or granulocytic myeloid derived suppressor cells. Advanced ePub. Journal of Dermatological Science (2016), DOI 10.1016/j.jdermsci.2016.04.013.
- Slatter TL, Royds JA, Pilbrow AP, Ahn A, Morrin H, Frampton C, Russell A, Moravec CS, Sweet WE, Tang WH, Currie MJ, Hung NA. The rs11515 polymorphism is more frequent and associated with aggressive breast tumors with increased ANRIL and decreased p16INK4A expression. Frontiers in Oncology; 5, 306, 2015. (Times cited=0).
- BD Hock, JL McKenzie, NB Cross, MJ Currie. Dynamic changes in myeloid derived suppressor cell subsets following renal transplant: A prospective study. Transplant Immunology; 32(3), 164-171. June 2015 (IF 1.8). (Times cited=0).
- Richardson AK, Currie MJ, Robinson BA, Morrin H, Phung Y, Pearson JF, Anderson TP, Potter JD, Walker LC. Cytomegalovirus and Epstein-Barr virus in breast cancer. PLoS One. 2015, Feb 27; 10(2):e0118989. (IF 3.5). (Times cited=1).
Publications
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
Hock, B. D., Mackenzie, K. A., Cross, N. B., Taylor, K. G., Currie, M. J., Robinson, B. A., Simcock, J. W., & McKenzie, J. L. (2012). Renal transplant recipients have elevated frequencies of circulating myeloid-derived suppressor cells. Nephrology Dialysis Transplantation, 27(1), 402-410. doi: 10.1093/ndt/gfr264
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
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
Pflüger, H.-J., Field, L. H., Nishino, H., & Currie, M. J. (2011). Neuromodulatory unpaired median neurons in the New Zealand tree weta, Hemideina femorata. Journal of Insect Physiology, 57(10), 1420-1430. doi: 10.1016/j.jinsphys.2011.07.010
Journal - Research Article
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
Hock, B. D., Mackenzie, K. A., Cross, N. B., Taylor, K. G., Currie, M. J., Robinson, B. A., Simcock, J. W., & McKenzie, J. L. (2012). Renal transplant recipients have elevated frequencies of circulating myeloid-derived suppressor cells. Nephrology Dialysis Transplantation, 27(1), 402-410. doi: 10.1093/ndt/gfr264
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
Pflüger, H.-J., Field, L. H., Nishino, H., & Currie, M. J. (2011). Neuromodulatory unpaired median neurons in the New Zealand tree weta, Hemideina femorata. Journal of Insect Physiology, 57(10), 1420-1430. doi: 10.1016/j.jinsphys.2011.07.010
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
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
Mackenzie, K. A., Wells, J. E., Lynn, K. L., Simcock, J. W., Robinson, B. A., Roake, J. A., & Currie, M. J. (2010). First and subsequent nonmelanoma skin cancers: Incidence and predictors in a population of New Zealand renal transplant recipients. Nephrology Dialysis Transplantation, 25, 300-306. doi: 10.1093/ndt/gfp482
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.
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
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.
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.
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
Jarvis, M. D., Rademaker, M. T., Ellmers, L. J., Currie, M. J., McKenzie, J. L., Palmer, B. R., Frampton, C. M., Richards, A. M., & Cameron, V. A. (2006). Comparison of infarct-derived and control ovine cardiac myofibroblasts in culture: Response to cytokines and natriuretic peptide receptor expression profiles. American Journal of Physiology: Heart & Circulatory Physiology, 291, H1952-H1958. doi: 10.1152/ajpheart.00764.2005
Journal - Research Other
Mackenzie, K. A., Simcock, J. W., Lainchbury, J. G., Currie, M. J., & Lynn, K. L. (2009). Myocardial metastasis of cutaneous squamous cell carcinoma in a renal transplant recipient [Case report]. Transplantation Proceedings, 41(10), 4414-4415. doi: 10.1016/j.transproceed.2009.09.056
