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Contact Details

Phone
+64 3 479 9190
Email
jisha.antony@otago.ac.nz

University Links

Position
Senior Research Fellow
Department
Department of Pathology (Dunedin)
Research summary
Chromatin organisation in cancer

Research

My research focuses on understanding how leukaemia associated mutations in chromatin organisers such as cohesin, impacts chromatin folding or causes translocations such as RUNX1-RUNX1T1. Our work has identified enhancer dysfunction as the major effect of cohesin mutation.

We have also shown that the impact of aberrant enhancer activity is most profound and causes gene expression dysregulation when cells have to respond to differentiation or external signalling cues.

We are currently working on determining whether enhancer dysfunction can be combated using enhancer blocking drugs or by individual targeting of enhancers using CRISPR-Cas9 technology. I am also using genome-wide CRISPR-Cas9 screens in cohesin mutant leukaemia cells to identify synthetic lethal targets that could be therapeutically targeted.

To study the impact of cohesin mutation on signalling events we are using induced pluripotent stem cells and differentiating them to haematopoietic cells to examine chromatin organisation and gene expression. The work is funded by Cancer Society and Health Research Council grants.

Publications

Banerjee, R., Ajithkumar, P., Keestra, N., Smith, J., Gimenez, G., Rodger, E. J., Eccles, M. R., Antony, J., Weeks, R. J., & Chatterjee, A. (2024). Targeted DNA methylation editing using an all-in-one system establishes paradoxical activation of EBF3. Cancers, 16, 898. doi: 10.3390/cancers16050898

Thomas, A. L., Marsman, J., Antony, J., Schierding, W., O'Sullivan, J. M., & Horsfield, J. A. (2021). Transcriptional regulation of RUNX1: An informatics analysis. Gene, 12(8), 1175. doi: 10.3390/genes12081175

Antony, J., Chin, C. V., & Horsfield, J. A. (2021). Cohesin mutations in cancer: Emerging therapeutic targets. International Journal of Molecular Sciences, 22(13), 6788. doi: 10.3390/ijms22136788

Chin, C. V., Antony, J., Ketharnathan, S., Labudina, A., Gimenez, G., Parsons, K. M., … Braithwaite, A., Guilford, P., … Horsfield, J. A. (2020). Cohesin mutations are synthetic lethal with stimulation of WNT signaling. eLIFE, 9, e61405. doi: 10.7554/eLife.61405

Antony, J., Gimenez, G., Taylor, T., Khatoon, U., Day, R., Morison, I. M., & Horsfield, J. A. (2020). BET inhibition prevents aberrant RUNX1 and ERG transcription in STAG2 mutant leukaemia cells. Journal of Molecular Cell Biology, 12(5), 397-399. doi: 10.1093/jmcb/mjz114

Banerjee, R., Ajithkumar, P., Keestra, N., Smith, J., Gimenez, G., Rodger, E. J., Eccles, M. R., Antony, J., Weeks, R. J., & Chatterjee, A. (2024). Targeted DNA methylation editing using an all-in-one system establishes paradoxical activation of EBF3. Cancers, 16, 898. doi: 10.3390/cancers16050898

Journal - Research Article

Antony, J., Chin, C. V., & Horsfield, J. A. (2021). Cohesin mutations in cancer: Emerging therapeutic targets. International Journal of Molecular Sciences, 22(13), 6788. doi: 10.3390/ijms22136788

Journal - Research Article

Thomas, A. L., Marsman, J., Antony, J., Schierding, W., O'Sullivan, J. M., & Horsfield, J. A. (2021). Transcriptional regulation of RUNX1: An informatics analysis. Gene, 12(8), 1175. doi: 10.3390/genes12081175

Journal - Research Article

Chin, C. V., Antony, J., Ketharnathan, S., Labudina, A., Gimenez, G., Parsons, K. M., … Braithwaite, A., Guilford, P., … Horsfield, J. A. (2020). Cohesin mutations are synthetic lethal with stimulation of WNT signaling. eLIFE, 9, e61405. doi: 10.7554/eLife.61405

Journal - Research Article

Leask, M., Dowdle, A., Salvesen, H., Topless, R., Fadason, T., Wei, W., … Marsman, J., Antony, J., … Merriman, T. R., & Horsfield, J. A. (2019). Functional urate-associated genetic variants influence expression of lincRNAs LINC01229 and MAFTRR. Frontiers in Genetics, 9, 733. doi: 10.3389/fgene.2018.00733

Journal - Research Article

Ketharnathan, S., Leask, M., Boocock, J., Phipps-Green, A. J., Antony, J., O'Sullivan, J. M., Merriman, T. R., & Horsfield, J. A. (2018). A non-coding genetic variant maximally associated with serum urate levels is functionally linked to HNF4A-dependent PDZK1 expression. Human Molecular Genetics, 27(22), 3964-3973. doi: 10.1093/hmg/ddy295

Journal - Research Article

Mehta, S. Y., Morten, B. C., Antony, J., Henderson, L., Lasham, A., Campbell, H., Cunliffe, H., Horsfield, J. A., … Braithwaite, A. W. (2018). Regulation of the interferon-gamma (IFN-γ) pathway by p63 and Δ133p53 isoform in different breast cancer subtypes. Oncotarget, 9(49), 29146-29161. doi: 10.18632/oncotarget.25635

Journal - Research Article

Schierding, W., Antony, J., Karhunen, V., Vääräsmäki, M., Franks, S., Elliott, P., … Horsfield, J. A., … Cutfield, W. S. (2018). GWAS on prolonged gestation (post-term birth): Analysis of successive Finnish birth cohorts. Journal of Medical Genetics, 55(1), 55-63. doi: 10.1136/jmedgenet-2017-104880

Journal - Research Article

Wei, J., Antony, J., Meng, F., MacLean, P., Rhind, R., Laible, G., & Oback, B. (2017). KDM4B-mediated reduction of H3K9me3 and H3K36me3 levels improves somatic cell reprogramming into pluripotency. Scientific Reports, 7, 7514. doi: 10.1038/s41598-017-06569-2

Journal - Research Article

Dasgupta, T., Antony, J., Braithwaite, A. W., & Horsfield, J. A. (2016). HDAC8 inhibition blocks SMC3 deacetylation and delays cell cycle progression without affecting cohesin-dependent transcription in MCF7 cancer cells. Journal of Biological Chemistry, 291(24), 12761-12770. doi: 10.1074/jbc.M115.704627

Journal - Research Article

Schierding, W., Antony, J., Cutfield, W. S., Horsfield, J. A., & O'Sullivan, J. M. (2016). Intergenic GWAS SNPs are key components of the spatial and regulatory network for human growth. Human Molecular Genetics, 25(15), 3372-3382. doi: 10.1093/hmg/ddw165

Journal - Research Article

Antony, J., Dasgupta, T., Rhodes, J. M., McEwan, M. V., Print, C. G., O'Sullivan, J. M., & Horsfield, J. A. (2015). Cohesin modulates transcription of estrogen-responsive genes. Biochimica et Biophysica Acta: Gene Regulatory Mechanisms, 1849(3), 257-269. doi: 10.1016/j.bbagrm.2014.12.011

Journal - Research Article

Marsman, J., O'Neill, A. C., Kao, B. R.-Y., Rhodes, J. M., Meier, M., Antony, J., Mönnich, M., & Horsfield, J. A. (2014). Cohesin and CTCF differentially regulate spatiotemporal runx1 expression during zebrafish development. Biochimica et Biophysica Acta: Gene Regulatory Mechanisms, 1839(1), 50-61. doi: 10.1016/j.bbagrm.2013.11.007

Journal - Research Article

O'Sullivan, J. M., Doynova, M. D., Antony, J., Pichlmuller, F., & Horsfield, J. A. (2014). Insights from space: Potential role of diet in the spatial organization of chromosomes. Nutrients, 6(12), 5724-5739. doi: 10.3390/nu6125724

Journal - Research Article

Antony, J., Oback, F., Chamley, L. W., Oback, B., & Laible, G. (2013). Transient JMJD2B-mediated reduction of H3K9me3 levels improves reprogramming of embryonic stem cells into cloned embryos. Molecular & Cellular Biology, 33(5), 974-983. doi: 10.1128/MCB.01014-12

Journal - Research Article

Antony, J., Gimenez, G., Taylor, T., Khatoon, U., Day, R., Morison, I. M., & Horsfield, J. A. (2020). BET inhibition prevents aberrant RUNX1 and ERG transcription in STAG2 mutant leukaemia cells. Journal of Molecular Cell Biology, 12(5), 397-399. doi: 10.1093/jmcb/mjz114

Journal - Research Other

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