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Contact Details

Phone
+64 3 479 7372
Email
tim.hore@otago.ac.nz
Position
Associate Professor
Department
Department of Anatomy
Qualifications
BSc(Hons)(Otago) PhD(ANU)
Research summary
Epigenetics and development

Research

Associate Professor Hore's research interests lie at the intersection between epigenetics and development. Epigenetics involves the modification of DNA and the histone proteins associated with it, and can have stable, poentially life-long effects upon the expression of genes. Methylation of CG dinucleotides is unique amongst epigenetic modifications in that there is a well-understood and elegant system by which it is propagated long-term following cell division and removal of the original methylating signal. From a developmental perspective, this 'epigenetic memory' is likely to be important in defining the identity of cells as they progressively become more differentiated and specialised.

Indeed, the most basal stem cells of the body distinctly lack CG methylation (<30%) (Ficz et al., 2013), yet accumulate CG methylation to levels above 70% as they commit to the earliest developmental lineages, a process which if disrupted is lethal to an embryo. Inline with hypothesis that DNA methylation is inversely correlated with developmental potency, active removal of DNA methylation can enhance the derivation of induced pluripotent stem cells (iPSCs, Costa et al., 2013). As such, research in this area is of great relevance to both regenerative medicine and animal transgenics.

Associate Professor Hore's current research is focussed upon harnessing DNA demethylation to create pluripotent cells efficiently and safely, work that involves collaboration with scientists at the Babraham Institute in the United Kingdom (Wolf Reik and Ferdinand von Meyenn) and Unversity of Stuttgart in Germany (Tomek Jurkowski). Associate Professor Hore and his team are also actively researching the consequences of epigenetic reprogramming and DNA demethylation in the germlines of divergent vertebrate models, and with others at Otago (Sheri Johnson and Neil Gemmell), the consequences this has upon transgenerational epigenetic inheritance.

His research has been funded by the Human Frontiers Science Program (2009–2014), EpiGeneSys (2011–2013), the University of Otago (2015–2016), and the Marsden Fund (2016–2019, led by Sheri Johnson). A full list of his publications can be found using the following link: https://scholar.google.co.uk/citations?user=TFZ-NEcAAAAJ&hl=en

Publications

Hore, T. A., von Meyenn, F., Ravichandran, M., Bachman, M., Ficz, G., Oxley, D., … Reik, W. (2016). Retinol and ascorbate drive erasure of epigenetic memory and enhance reprogramming to naĭve pluripotency by complementary mechanisms. PNAS, 113(43), 12202-12207. doi: 10.1073/pnas.1608679113 Journal - Research Article

Lee, H. J., Hore, T. A., & Reik, W. (2014). Reprogramming the methylome: Erasing memory and creating diversity. Cell Stem Cell, 14(6), 710-719. doi: 10.1016/j.stem.2014.05.008 Journal - Research Article

Peat, J. R., Dean, W., Clark, S. J., Krueger, F., Smallwood, S. A., Ficz, G., … Hore, T. A., & Reik, W. (2014). Genome-wide bisulfite sequencing in zygotes identifies demethylation targets and maps the contribution of TET3 oxidation. Cell Reports, 9(6), 1990-2000. doi: 10.1016/j.celrep.2014.11.034 Journal - Research Article

Ficz, G., Hore, T. A., Santos, F., Lee, H. J., Dean, W., Arand, J., … Reik, W. (2013). FGF signaling inhibition in ESCs drives rapid genome-wide demethylation to the epigenetic ground state of pluripotency. Cell Stem Cell, 13(3), 351-359. doi: 10.1016/j.stem.2013.06.004 Journal - Research Article

Costa, Y., Ding, J., Theunissen, T. W., Faiola, F., Hore, T. A., Shliaha, P. V., … Wang, J. (2013). NANOG-dependent function of TET1 and TET2 in establishment of pluripotency. Nature, 495(7441), 370-374. doi: 10.1038/nature11925 Journal - Research Article

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