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Margreet VissersPrincipal Investigator
Associate Dean (Research)

BSc(Hons)(Cant) MSc PhD(Otago)

Email margreet.vissers@otago.ac.nz 
Tel +64 3 364 1524

Research interests

Vitamin C and cancer

Most of my current research revolves around determining the biological functions of vitamin C (ascorbate), which is widely considered to be an important natural antioxidant. However, ascorbate is also an essential co-factor for a family of enzymes, the 2-oxoglutarate-dependent dioxygenases, which control many biological processes, ranging from the stress response to hypoxia, to the regulation of epigenetic enzymes. These processes are important in cancer and we are investigating the contribution of ascorbate to cancer growth as a result of its co-factor activity for these enzymes. We are planning clinical trials to determine the impact of ascorbate on the processes involved in cancer cell biology.

Vitamin C and immunity

The cofactor activities of ascorbate are likely to influence many biological processes that impact on health and disease, and our aim is to understand the extent of this involvement in the functioning of the immune system. My research has shown that ascorbate affects white blood cell function, and we have an interest in the role of ascorbate in acute inflammatory diseases such as pneumonia and sepsis.

Vitamin C and optimal health

We have investigated the comparative bioavailability of vitamin C from different sources (i.e. food-derived or synthetic) to organs and tissues in an animal model and human subjects. This research will help to inform the debate around the appropriate Nutrient Reference Value and Recommended Dietary Intake for vitamin C. Ascorbate acts as a cofactor for the enzymatic synthesis of mood and energy controlling hormones. We have investigated the association of vitamin C intake from an excellent food source (kiwifruit) with measures of subjective mood, including fatigue, and shown that a high vitamin C diet can improve mood and energy levels. This preliminary research will be followed up with a larger clinical study.

White blood cells and inflammation

My research interests also include the investigation of cellular responses to stress, in particular stress resulting from exposure to oxidants. I have extensive experience in working with inflammatory cells, particularly neutrophils, as a source of highly reactive oxidants. Neutrophils generate hypochlorous acid (HOCl), i.e. household bleach, which is known for its anti-microbial activity. HOCl also reacts with many biological targets, as we are investigating how it damages cells and tissues, and how it contributes to the many deleterious effects of chronic inflammatory diseases such as atherosclerosis. The oxidative stress-related processes we are most interested in are apoptosis (cell clearance from sites of inflammation), cell signalling (e.g. nuclear factor-kB; NFkB, and hypoxia-inducible factor 1a; HIF-1) and cytotoxicity (cell death).

Keywords: cancer, immunity, vitamin C (ascorbate), inflammation, atherosclerosis, oxidative stress, antioxidants.

In the media

Professor Margreet Vissers was featured in Radio New Zealand's The Science Of... Vitamin C in August 2017.

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Publications

Wohlrab, C., Vissers, M. C. M., Burgess, E. R., Nonis, M., Phillips, E., Robinson, B. A., & Dachs, G. U. (2021). Limited association between ascorbate concentrations and vitamin C transporters in renal cell carcinoma cells and clinical samples. Cellular Physiology & Biochemistry, 55, 553-568. doi: 10.33594/000000435

Smith-Díaz, C. C., Magon, N. J., McKenzie, J. L., Hampton, M. B., Vissers, M. C. M., & Das, A. B. (2021). Ascorbate inhibits proliferation and promotes myeloid differentiation in TP53-mutant leukemia. Frontiers in Oncology, 11, 709543. doi: 10.3389/fonc.2021.709543

Crake, R. L. I., Burgess, E. R., Royds, J. A., Phillips, E., Vissers, M. C. M., & Dachs, G. U. (2021). The role of 2-oxoglutarate dependent dioxygenases in gliomas and glioblastomas: A review of epigenetic reprogramming and hypoxic responses. Frontiers in Oncology, 11, 619300. doi: 10.3389/fonc.2021.619300

Pearson, A. G., Pullar, J. M., Cook, J., Spencer, E. S., Vissers, M. C. M., Carr, A. C., & Hampton, M. B. (2021). Peroxiredoxin 2 oxidation reveals hydrogen peroxide generation within erythrocytes during high-dose vitamin C administration. Redox Biology, 43, 101980. doi: 10.1016/j.redox.2021.101980

Ang, A. D., Vissers, M. C. M., Burgess, E. R., Currie, M. J., & Dachs, G. U. (2021). Gene and protein expression is altered by ascorbate availability in murine macrophages cultured under tumour-like conditions. Antioxidants, 10(3), 430. doi: 10.3390/antiox10030430

Chen, Q., & Vissers, M. C. M. (Eds.). (2020). Cancer and vitamin C. Boca Raton, FL: CRC Press, 174p.

Edited Book - Research

Chen, Q., & Vissers, M. C. M. (Eds.). (2020). Vitamin C: New biochemical and functional insights. Boca Raton, FL: CRC Press, 256p.

Edited Book - Research

Vissers, M. C. M., Hampton, M. B., & Kettle, A. J. (Eds.). (2018). Hydrogen peroxide metabolism in health and disease. Boca Raton, FL: CRC Press, 456p.

Edited Book - Research

Ang, A., Vissers, M. C. M., & Pullar, J. M. (2020). Vitamin C in immune cell function. In Q. Chen & M. C. M. Vissers (Eds.), Vitamin C: New biochemical and functional insights. (pp. 137-159). Boca Raton, FL: CRC Press.

Chapter in Book - Research

Pullar, J. M., & Vissers, M. C. M. (2020). Role of Vitamin C in chronic wound healing. In Q. Chen & M. C. M. Vissers (Eds.), Vitamin C: New biochemical and functional insights. (pp. 161-179). Boca Raton, FL: CRC Press.

Chapter in Book - Research

Vissers, M. C. M., & Das, A. B. (2020). Ascorbate as an enzyme cofactor. In Q. Chen & M. C. M. Vissers (Eds.), Vitamin C: New biochemical and functional insights. (pp. 71-98). Boca Raton, FL: CRC Press.

Chapter in Book - Research

Vissers, M. C. M., Pullar, J. M., & Smirnoff, N. (2020). Chemistry and biochemistry of vitamin C in mammalian systems. In Q. Chen & M. C. M. Vissers (Eds.), Vitamin C: New biochemical and functional insights. (pp. 25-37). Boca Raton, FL: CRC Press.

Chapter in Book - Research

Vissers, M. C. M., Pullar, J. M., & Peskin, A. V. (2018). Myeloperoxidase-derived oxidants hypochlorous acid and chloramines: Microbicidal marvels and inflammatory mischief makers. In M. C. M. Vissers, M. B. Hampton & A. J. Kettle (Eds.), Hydrogen peroxide metabolism in health and disease. (pp. 305-326). Boca Raton, FL: CRC Press.

Chapter in Book - Research

Vissers, M. C. M., Carr, A. C., Pullar, J. M., & Bozonet, S. M. (2013). The bioavailability of vitamin C from kiwifruit. In M. Boland & P. J. Moughan (Eds.), Nutritional benefits of kiwifruit. (pp. 125-147). Waltham, MA: Academic Press. doi: 10.1016/b978-0-12-394294-4.00007-9

Chapter in Book - Research

Ang, A. D., Vissers, M. C. M., Burgess, E. R., Currie, M. J., & Dachs, G. U. (2021). Gene and protein expression is altered by ascorbate availability in murine macrophages cultured under tumour-like conditions. Antioxidants, 10(3), 430. doi: 10.3390/antiox10030430

Journal - Research Article

Dachs, G. U., Gandhi, J., Wohlrab, C., Carr, A. C., Morrin, H. R., Pullar, J. M., Bayer, S. B., Eglinton, T. W., Robinson, B. A., & Vissers, M. C. M. (2021). Vitamin C administration by intravenous infusion increases tumor ascorbate content in patients with colon cancer: A clinical intervention study. Frontiers in Oncology, 10, 600715. doi: 10.3389/fonc.2020.600715

Journal - Research Article

Fletcher, B. D., Flett, J. A. M., Wickham, S.-R., Pullar, J. M., Vissers, M. C. M., & Conner, T. S. (2021). Initial evidence of variation by ethnicity in the relationship between vitamin C status and mental states in young adults. Nutrients, 13, 792. doi: 10.3390/nu13030792

Journal - Research Article

Pearson, A. G., Pullar, J. M., Cook, J., Spencer, E. S., Vissers, M. C. M., Carr, A. C., & Hampton, M. B. (2021). Peroxiredoxin 2 oxidation reveals hydrogen peroxide generation within erythrocytes during high-dose vitamin C administration. Redox Biology, 43, 101980. doi: 10.1016/j.redox.2021.101980

Journal - Research Article

Smith-Díaz, C. C., Magon, N. J., McKenzie, J. L., Hampton, M. B., Vissers, M. C. M., & Das, A. B. (2021). Ascorbate inhibits proliferation and promotes myeloid differentiation in TP53-mutant leukemia. Frontiers in Oncology, 11, 709543. doi: 10.3389/fonc.2021.709543

Journal - Research Article

Wohlrab, C., Vissers, M. C. M., Burgess, E. R., Nonis, M., Phillips, E., Robinson, B. A., & Dachs, G. U. (2021). Limited association between ascorbate concentrations and vitamin C transporters in renal cell carcinoma cells and clinical samples. Cellular Physiology & Biochemistry, 55, 553-568. doi: 10.33594/000000435

Journal - Research Article

Conner, T. S., Fletcher, B. D., Pullar, J. M., Spencer, E., Mainvil, L. A., & Vissers, M. C. M. (2020). KiwiC for vitality: Results of a randomized placebo-controlled trial testing the effects of kiwifruit or vitamin C tablets on vitality in adults with low vitamin C levels. Nutrients, 12, 2898. doi: 10.3390/nu12092898

Journal - Research Article

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

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

Journal - Research Article

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

Journal - Research Article

Talla, U., Bozonet, S. M., Parker, H. A., Hampton, M. B., & Vissers, M. C. M. (2019). Prolonged exposure to hypoxia induces an autophagy-like cell survival program in human neutrophils. Journal of Leukocyte Biology, 106, 1367-1379. doi: 10.1002/jlb.4a0319-079rr

Journal - Research Article

Tang, J. S., Bozonet, S. M., McKenzie, J. L., Anderson, R. F., Melton, L. D., & Vissers, M. C. M. (2019). Physiological concentrations of blueberry-derived phenolic acids reduce monocyte adhesion to human endothelial cells. Molecular Nutrition & Food Research, 63, 1900478. doi: 10.1002/mnfr.201900478

Journal - Research Article

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

Journal - Research Article

Pullar, J. M., Carr, A. C., Bozonet, S. M., & Vissers, M. C. M. (2018). High vitamin C status is associated with elevated mood in male tertiary students. Antioxidants, 7(7), 91. doi: 10.3390/antiox7070091

Journal - Research Article

Tang, J. S., Vissers, M. C. M., Anderson, R. F., Sreebhavan, S., Bozonet, S. M., Scheepens, A., & Melton, L. D. (2018). Bioavailable blueberry-derived phenolic acids at physiological concentrations enhance Nrf2-regulated antioxidant responses in human vascular endothelial cells. Molecular Nutrition & Food Research, 62(5), 1700647. doi: 10.1002/mnfr.201700647

Journal - Research Article

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

Journal - Research Article

Brookie, K. L., Mainvil, L. A., Carr, A. C., Vissers, M. C. M., & Conner, T. S. (2017). The development and effectiveness of an ecological momentary intervention to increase daily fruit and vegetable consumption in low-consuming young adults. Appetite, 108, 32-41. doi: 10.1016/j.appet.2016.09.015

Journal - Research Article

Conner, T. S., Brookie, K. L., Carr, A. C., Mainvil, L. A., & Vissers, M. C. M. (2017). Let them eat fruit! The effect of fruit and vegetable consumption on psychological well-being in young adults: A randomized controlled trial. PLoS ONE, 12(2), e0171206. doi: 10.1371/journal.pone.0171206

Journal - Research Article

Mitsuya, K., Parker, A. N., Liu, L., Ruan, J., Vissers, M. C. M., & Myatt, L. (2017). Alterations in the placental methylome with maternal obesity and evidence for metabolic regulation. PLoS ONE, 12(10), e0186115. doi: 10.1371/journal.pone.0186115

Journal - Research Article

Pearson, J. F., Pullar, J. M., Wilson, R., Spittlehouse, J. K., Vissers, M. C. M., Skidmore, P. M. L., Willis, J., Cameron, V. A., & Carr, A. C. (2017). Vitamin C status correlates with markers of metabolic and cognitive health in 50-year-olds: Findings of the CHALICE Cohort Study. Nutrients, 9(8), 831. doi: 10.3390/nu9080831

Journal - Research Article

Pullar, J. M., Carr, A. C., & Vissers, M. C. M. (2017). The roles of vitamin C in skin health. Nutrients, 9(8), 866. doi: 10.3390/nu9080866

Journal - Research Article

Pullar, J. M., Carr, A. C., Bozonet, S. M., Rosengrave, P., Kettle, A. J., & Vissers, M. C. M. (2017). Elevated seminal plasma myeloperoxidase is associated with a decreased sperm concentration in young men. Andrology, 5(3), 431-438. doi: 10.1111/andr.12327

Journal - Research Article

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

Journal - Research Article

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

Journal - Research Article

Carr, A. C., Pullar, J. M., Bozonet, S. M., & Vissers, M. C. M. (2016). Marginal ascorbate status (Hypovitaminosis C) results in an attenuated response to vitamin C supplementation. Nutrients, 8(6), 341. doi: 10.3390/nu8060341

Journal - Research Article

Bozonet, S. M., Carr, A. C., Pullar, J. M., & Vissers, M. C. M. (2015). Enhanced human neutrophil vitamin C status, chemotaxis and oxidant generation following dietary supplementation with vitamin C-rich SunGold kiwifruit. Nutrients, 7(4), 2574-2588. doi: 10.3390/nu7042574

Journal - Research Article

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

Journal - Research Article

Wilkie-Grantham, R. P., Magon, N. J., Harwood, D. T., Kettle, A. J., Vissers, M. C., Winterbourn, C. C., & Hampton, M. B. (2015). Myeloperoxidase-dependent lipid peroxidation promotes the oxidative modification of cytosolic proteins in phagocytic neutrophils. Journal of Biological Chemistry, 290(15), 9896-9905. doi: 10.1074/jbc.M114.613422

Journal - Research Article

Carr, A. C., Vissers, M. C. M., & Cook, J. S. (2014). The effect of intravenous vitamin C on cancer- and chemotherapy-related fatigue and quality of life. Frontiers in Oncology, 4, 283. doi: 10.3389/fonc.2014.00283

Journal - Research Article

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

Journal - Research Article

Kuiper, C., & Vissers, M. C. M. (2014). Ascorbate as a cofactor for Fe-and 2-oxoglutarate dependent dioxygenases: Physiological activity in tumour growth and progression. Frontiers in Oncology, 4, 359. doi: 10.3389/fonc.2014.00359

Journal - Research Article

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

Journal - Research Article

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

Journal - Research Article

Kuiper, C., Vissers, M. C. M., & Hicks, K. O. (2014). Pharmacokinetic modelling of ascorbate diffusion through normal and tumour tissue. Free Radical Biology & Medicine, 77, 340-352. doi: 10.1016/j.freeradbiomed.2014.09.023

Journal - Research Article

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

Journal - Research Article

Carr, A. C., & Vissers, M. C. M. (2013). Synthetic or food-derived vitamin C—are they equally bioavailable? Nutrients, 5(11), 4284-4304. doi: 10.3390/nu5114284

Journal - Research Article

Carr, A. C., Bozonet, S. M., & Vissers, M. C. M. (2013). A randomised cross-over pharmacokinetic bioavailability study of synthetic versus kiwifruit-derived vitamin C. Nutrients, 5(11), 4451-4461. doi: 10.3390/nu5114451

Journal - Research Article

Carr, A. C., Bozonet, S. M., Pullar, J. M., & Vissers, M. C. M. (2013). Mood improvement in young adult males following supplementation with gold kiwifruit, a high-vitamin C food. Journal of Nutritional Science, 2, e24. doi: 10.1017/jns.2013.12

Journal - Research Article

Carr, A. C., Bozonet, S. M., Pullar, J. M., Simcock, J. W., & Vissers, M. C. M. (2013). A randomized steady-state bioavailability study of synthetic versus natural (kiwifruit-derived) vitamin C. Nutrients, 5(9), 3684-3695. doi: 10.3390/nu5093684

Journal - Research Article

Carr, A. C., Bozonet, S. M., Pullar, J. M., Simcock, J. W., & Vissers, M. C. M. (2013). Human skeletal muscle ascorbate is highly responsive to changes in vitamin C intake and plasma concentrations. American Journal of Clinical Nutrition, 97, 800-807. doi: 10.3945/ajcn.112.053207

Journal - Research Article

Carr, A. C., Pullar, J. M., Moran, S., & Vissers, M. C. M. (2012). Bioavailability of vitamin C from kiwifruit in non-smoking males: Determination of ‘healthy’ and ‘optimal’ intakes. Journal of Nutritional Science, 1, e14. doi: 10.1017/jns.2012.15

Journal - Research Article

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