Research Fellow
BBiomedSc(Hons), PhD (Otago)
Research interests
My research interests lie at the intersection of inflammation, ageing, cancer and epigenetics. By investigating the dynamic changes in epigenetic regulation associated with inflammation-induced carcinogenesis and ageing, my aim is to identify novel therapeutic targets and interventions for improving patient outcomes in cancer and age-related disorders.
I am particularly interested in how immune cell- and/or mitochondria-derived oxidants influence the enzymes involved in DNA methylation. We have seen that exposure to the oxidants hydrogen peroxide (H2O2) and glycine chloramine inactivate DNA methyltransferase (DNMT) activity via direct inhibition and the depletion of S-adenosyl methionine (SAM). The oxidation of DNMT led to site-specific changes in DNA methylation patterns and corresponding transcriptional perturbations in T-lymphoma cells. Many of these changes were associated with pathways important to cancer progression such as proliferation, differentiation, autophagy and apoptosis1–3.
My current work, generously funded by the Canterbury Medical Research Foundation, is exploring how bacterial lipopolysaccharide found in abundance in the gut of patients with colorectal cancer influences immune cell oxidant release and modify epigenetic patterns in this cancer.
I am also exploring how mitochondrial dysfunction influences the epigenetics and differentiation of haematopoietic stem cells with implications for ageing, haematological disease and cancer.
I am currently taking on highly motivated postgraduate students and/or medical students with a genuine interest in these fields.
1. Das, A. B., Seddon A.R. et al. Free Radic. Biol. Med. 170, 131–149 (2021)
2. Seddon, A. R. et al. Epigenetics and Chromatin 14, 1–16 (2021)
3. Seddon, A. R. et al. Hum. Mol. Genet. 00, 1–17 (2022)
Otago profile
As an undergraduate biology student, Annika Seddon decided she wanted to do postgraduate research in the field of cancer.
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Publications
Seddon, A., Das, A., Hampton, M., & Stevens, A. (2023). Understanding how immune oxidants can drive epigenetic change. Proceedings of the European Society of Human Genetics (ESHG) European Human Genetics Hybrid Conference. P21.003.C. Retrieved from https://www.eshg.org/home
Seddon, A. R., Das, A. B., Hampton, M. B., & Stevens, A. J. (2023). Site-specific decreases in DNA methylation in replicating cells following exposure to oxidative stress. Human Molecular Genetics, 32(4), 632-648. doi: 10.1093/hmg/ddac232
Seddon, A. (2022, December). Epigenetic regulation of gene expression following exposure to neutrophil oxidants. Verbal presentation at the Society for Free Radical Research (SFRR) Australasia & Japan Conference: Redox Pathways in Biology & Medicine, Christchurch, New Zealand.
Seddon, A. (2022, August). Site-specific decreases in DNA methylation in replicating cells following exposure to oxidative stress. Poster session presented at the Cancer Satellite Meeting: Queenstown Research Week, Queenstown, New Zealand.
Seddon, A. R., Liau, Y., Pace, P. E., Miller, A. L., Das, A. B., Kennedy, M. A., Hampton, M. B., & Stevens, A. J. (2021). Genome-wide impact of hydrogen peroxide on maintenance DNA methylation in replicating cells. Epigenetics & Chromatin, 14(1), 17. doi: 10.1186/s13072-021-00388-6