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Andrew Das

Postdoctoral Fellow

MB ChB, PhD (Otago)

Email andrew.das@otago.ac.nz 
Tel 64 3 378 6159

Research interests

Dr Andrew Das completed his combined medical and postgraduate studies (MBChB/PhD) at the University of Otago. For the PhD component of his degree he worked with Professors' Tony Kettle and Christine Winterbourn in the area of free radical biochemistry. He also developed expertise in mass spectrometry (peptide, protein and small molecule analysis), experimental biochemistry (free radical trapping, protein purification, enzyme assays and protein electrophoresis) and experience with cell and molecular biology (cell culture, transfection, PCR and cloning). During this time, he became very interested in epigenetic mechanisms that play a role in development and cancer.

Together with Professor Margreet Vissers, he is investigating the potential role of ascorbate as an epigenetic therapeutic in specific subtypes of acute myeloid leukaemia. The long-term goal is to identify epigenetic subtypes of AML that may respond to treatment. A second project with Professor Hampton is investigating whether reactive oxidant species produced by immune cells can regulate affect the epigenetic identity of neighbouring cells.

In 2018, Dr Das was awarded a NZ Society of Oncology Fellowship (Roche Translational Cancer Research Fellowship) to enable developing the epigenetic and bioinformatic expertise required for these projects. Dr Das was also recently awarded a John Gavin Postdoctoral Research Fellowship by the Cancer Research Trust.

What is epigenetics?

Each of us begins life as a single cell, a fertilised egg. We then embark on a journey that culminates in our birth. Over these nine months or so, an incredible process takes place, the development of all the various cells and organs that make up our body. Because every cell has the same DNA code, extra markings are required to tell each cell which part of the DNA code they should be using. In other words, these epigenetic markings help cells remember their identity. Epigenetic markings can be on the DNA itself, or on the proteins that DNA is wrapped tightly around to package it inside our cells. A similar process occurs on a daily basis, where your body produces billions of blood cells across a wide range of cell types. These cells all come from haematopoietic stem cells located in the bone marrow, with each type requiring different epigenetic markings to guide their development.

What does this have to do with leukaemia?

When cells acquire mutations in DNA that affect this process, they become dysfunctional and potentially cancerous. This is in fact what we see with AML. Interestingly, these mutations appear earlier in the course of the disease and drive the development of AML. Because epigenetic markings can be written or erased, the effects are potentially reversible. A prime example is mutations that affect the activity of the enzyme TET2. TET2 is involved in erasing a marking called methylation, and requires ascorbate for optimal activity. Furthermore, supplying additional ascorbate can increase the activity of TET2. These observations have led to the postulation that patients with decreased TET2 activity could benefit from treatment with ascorbate. The team are currently using a number of different approaches to investigate this hypothesis. So far, this work led to a first-in-human demonstration that ascorbate might provide benefit as an adjunct treatment where mutations affect the activity of the DNA demethylase TET2. Although clinical trials explicitly designed to address this possibility are required, the insights provided by the case study will assist in their design.

In the media

Dr Andrew Das was interviewed on Radio New Zealand by Kim Hill in September 2018 about his research into the role of epigenetics in cancer.

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Publications

Das, A. B., Kakadia, P. M., Wojcik, D., Pemberton, L., Browett, P. J., Bohlander, S. K., & Vissers, M. C. M. (2019). Clinical remission following ascorbate treatment in a case of acute myeloid leukemia with mutations in TET2 and WT1. Blood Cancer Journal, 9, 82. doi: 10.1038/s41408-019-0242-4

Das, A. B., Kakadia, P. M., Wojcik, D., Pemberton, L., Browett, P. J., Bohlander, S. K., & Vissers, M. C. M. (2019). Ascorbate targets acute myeloid leukaemia subclones with mutations that affect TET2 activity. Proceedings, 5(1), 3 (6.6). doi: 10.3390/proceedings2019005003

Das, A. B., Sadowska-Bartosz, I., Königstorfer, A., Kettle, A. J., & Winterbourn, C. C. (2018). Superoxide dismutase protects ribonucleotide reductase from inactivation in yeast. Free Radical Biology & Medicine, 116, 114-122. doi: 10.1016/j.freeradbiomed.2018.01.001

Vissers, M. C. M., & Das, A. B. (2018). Potential mechanisms of action for vitamin C in cancer: Reviewing the evidence. Frontiers in Physiology, 9, 809. doi: 10.3389/fphys.2018.00809

Vissers, M. C. M., Das, A., & Dachs, G. U. (2018). The 2-oxoglutarate-dependent dioxygenases and their role in cancer development, growth and metastasis. Proceedings of the New Zealand Society for Oncology (NZSO) Conference. Retrieved from http://www.nzsoncology.org.nz/

Journal - Research Article

Das, A. B., Sadowska-Bartosz, I., Königstorfer, A., Kettle, A. J., & Winterbourn, C. C. (2018). Superoxide dismutase protects ribonucleotide reductase from inactivation in yeast. Free Radical Biology & Medicine, 116, 114-122. doi: 10.1016/j.freeradbiomed.2018.01.001

Das, A. B., Nauser, T., Koppenol, W. H., Kettle, A. J., Winterbourn, C. C., & Nagy, P. (2014). Rapid reaction of superoxide with insulin-tyrosyl radicals to generate a hydroperoxide with subsequent glutathione addition. Free Radical Biology & Medicine, 70, 86-95. doi: 10.1016/j.freeradbiomed.2014.02.006

Nagy, P., Lechte, T. P., Das, A. B., & Winterbourn, C. C. (2012). Conjugation of glutathione to oxidized tyrosine residues in peptides and proteins. Journal of Biological Chemistry, 287(31), 26068-26076. doi: 10.1074/jbc.M112.371690

Das, A. B., Nagy, P., Abbott, H. F., Winterbourn, C. C., & Kettle, A. J. (2010). Reactions of superoxide with the myoglobin tyrosyl radical. Free Radical Biology & Medicine, 48, 1540-1547. doi: 10.1016/j.freeradbiomed.2010.02.039

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Journal - Research Other

Das, A. B., Kakadia, P. M., Wojcik, D., Pemberton, L., Browett, P. J., Bohlander, S. K., & Vissers, M. C. M. (2019). Clinical remission following ascorbate treatment in a case of acute myeloid leukemia with mutations in TET2 and WT1. Blood Cancer Journal, 9, 82. doi: 10.1038/s41408-019-0242-4

Vissers, M. C. M., & Das, A. B. (2018). Potential mechanisms of action for vitamin C in cancer: Reviewing the evidence. Frontiers in Physiology, 9, 809. doi: 10.3389/fphys.2018.00809

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Conference Contribution - Published proceedings: Abstract

Das, A. B., Kakadia, P. M., Wojcik, D., Pemberton, L., Browett, P. J., Bohlander, S. K., & Vissers, M. C. M. (2019). Ascorbate targets acute myeloid leukaemia subclones with mutations that affect TET2 activity. Proceedings, 5(1), 3 (6.6). doi: 10.3390/proceedings2019005003

Vissers, M. C. M., Das, A., & Dachs, G. U. (2018). The 2-oxoglutarate-dependent dioxygenases and their role in cancer development, growth and metastasis. Proceedings of the New Zealand Society for Oncology (NZSO) Conference. Retrieved from http://www.nzsoncology.org.nz/

Das, A., Morison, I., Bohlander, S., & Vissers, M. (2018). The potential use of ascorbate as an epigenetic therapeutic in acute myeloid leukaemia. Proceedings of the New Zealand Society for Oncology (NZSO) Conference. Retrieved from http://www.nzsoncology.org.nz/

Nagy, P., Das, A., Nauser, T., Koppenol, W. H., Kettle, A. J., & Winterbourn, C. C. (2015). Superoxide-mediated post-translational modification of tyrosine residues. Free Radical Biology & Medicine, 86(Suppl. 1), (pp. S17-S18). doi: 10.1016/j.freeradbiomed.2015.07.073

Das, A., Nagy, P., Lecthe, T., Koppenol, W. H., Winterbourn, C. C., & Kettle, A. (2013). Detection of glutathione conjugated to oxidised tyrosine residues on proteins. Free Radical Biology & Medicine, 65(Suppl. 2), (pp. S55). doi: 10.1016/j.freeradbiomed.2013.10.520

Das, A. B., Nagy, P., Lechte, T., Kettle, A. J., & Winterbourn, C. C. (2012). Conjugation of glutathione to oxidised tyrosine residues on proteins. Proceedings of the Oxygen Theme Meeting. (pp. 7). Dunedin, New Zealand: University of Otago. Retrieved from https://www.otago.ac.nz/research/otago051864.pdf

Das, A. B., Nagy, P., Abbott, H., Winterbourn, C. C., & Kettle, A. J. (2009). Reactions of superoxide with the myoglobin tyrosyl radical. Free Radical Biology and Medicine. 47(Suppl. 1), (pp. S74). [Abstract]

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Conference Contribution - Poster Presentation (not in published proceedings)

Das, A. B., Kakadia, P. M., Morison, I. M., Bohlander, S. K., & Vissers, M. C. M. (2018, August). The potential use of ascorbate as an epigenetic therapeutic in acute myeloid leukaemia. Poster session presented at the Queenstown Molecular Biology (QMB) Meetings, Queenstown, New Zealand.

Das, A., Morison, I., Kennedy, M., & Vissers, M. (2018, April). The potential use of ascorbate as an epigenetic therapeutic in acute myeloid leukaemia by enhancing 2-oxoglutarate dependent dioxygenase activity. Poster session presented at the Keystone Symposium: Therapeutic Targeting of Hypoxia-Sensitive Pathways, Oxford, UK.

Das, A., Morison, I., Kennedy, M., & Vissers, M. (2017, October). The potential use of ascorbate as an epigenetic drug in acute myeloid leukaemia. Poster session presented at the New Zealand Society for Oncology (NZSO) Conference, Auckland, New Zealand.

Das, A. B., Nagy, P., Lechte, T., Winterbourn, C. C., & Kettle, A. J. (2013, August). Detection of glutathione conjugated to oxidized tyrosine residues on protein. Poster session presented at the Queenstown Molecular Biology (QMB) Meetings, Queenstown, New Zealand.

Das, A. B., Nagy, P., Abbott, H., Winterbourn, C. C., & Kettle, A. J. (2009, September). Superoxide mediated protein oxidation: A potential mechanism for superoxide toxicity. Poster session presented at the Third Annual Division of Health Sciences Research Forum, Wellington, New Zealand.

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Conference Contribution - Verbal presentation and other Conference outputs

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.

Das, A. (2008, November). Reactions of superoxide with the myoglobin tyrosol radical. Verbal presentation at the Society for Free Radical Research Australasia Conference, Melbourne, Australia.

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Awarded Doctoral Degree

Das, A. B. (2017). The reactions of superoxide with tyrosyl radicals on proteins (PhD). University of Otago, Dunedin, New Zealand. Retrieved from http://hdl.handle.net/10523/7065

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