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Phillippa Taberlay

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Phillippa Taberlay

Phillippa Taberlay

NHMRC Career Development Fellow, Senior Research Fellow

Room 437A, Medical Sciences Precinct 2, Hobart CBD Campuses

03 6226 7771 (phone)

Phillippa.Taberlay@utas.edu.au

Dr Phillippa Taberlay is a NHMRC Career Development Fellow and Senior Research Fellow in the School of Medicine, College of Health and Medicine. Her research centres on understanding distal regulatory elements and three-dimensional aspects of gene control, and uses cutting-edge methods to delineate mechanisms of epigenetic reprogramming in development, cancer and neurodegenerative disorders.

Biography

Phillippa attained her Bachelor of Science majoring in Biochemistry, Microbiology and Immunology from the University of Tasmania in 2002, and graduated with a Bachelor of Science (First Class Honours) in Biochemistry and Molecular Biology in 2003. She then joined the laboratory of Dr Adele Holloway where she sought to understand how leukaemic fusion proteins disrupt epigenetic mechanisms in Acute Myeloid Leukaemia and was awarded her PhD for this work from the Menzies Research Institute of the University of Tasmania in 2008.

Phillippa undertook her post-doctoral research training in the laboratory of Professor Peter Jones at the University of Southern California, USA (2008-2011). Her discovery that enhancer epigenetic states underpin cell reprogramming (Taberlay, Cell 2011) was an advance for the field that has shaped new theories of epigenetic regulation. Her early-career research has also received two prestigious Faculty of 1000 recommendations, and was named as one of the Top Clinical Advances 2012 (American Society of Clinical Oncology). Phillippa co-developed the NOMe-Seq technique, described as an “impressive” and “ingenious innovation” and named as a Top 10 Innovation of 2013 that has since been commercialised. In 2011, Phillippa established her research group within the Epigenetics Research Program at the Garvan Institute of Medical Research under Professor Susan Clark, where she developed several new independent and collaborative projects, including cutting-edge technologies to map higher-order (3D) genome structures inside cells.

Phillippa holds a highly competitive NHMRC Career Development Fellowship and has recently returned to the University of Tasmania to establisher her laboratory within the School of Medicine. She has published her work in prominent international journals including Cell, Genome Research, Cancer Cell and PNAS.

Career summary

Qualifications

  • BSc, University of Tasmania, Australia, 2002
  • BSc (1st Class Hons), University of Tasmania, Australia, 2003
  • PhD, Regulation of Gene Expression by the RUNX1 Transcription Factor, University of Tasmania, Australia, 2008

Memberships

Professional practice

  • Australian Epigenetics Alliance (AEpiA; National Scientific Advisory Board and National Conference Committee)
  • American Association of Cancer Research (AACR)
  • Australasian Genome Technologies Association (AGTA)
  • Australasian Neuroscience Society (ANS)
  • Australian Bioinformatics & Computational Biology Society (ABACBS)
  • Australian Society for Medical Research (ASMR; Co-Convenor, Tasmania)

Administrative expertise

Ability to plan, lead and execute large epigenomic studies; >15 years experience in a diverse range of epigenetic and molecular biology assays with emphasis on sequencing (ChIP-seq, NOMe-seq, BS-seq, RNA-seq, HiC-seq, Capture-seq); analysis and biological interpretation of genome-scale data and epigenetic mechanisms.

Teaching

Epigenomics, Epigenetics, Epigenetic Mechanisms, Chromatin, Molecular Biology, Next-Generation Sequencing, Assay Development, Genomics, Computational Biology, Development, Cancer, Alzheimer’s Disease

Research Invitations

Phillippa has received invitations to speak atsix National conferences, including one keynote and three international conferences, and she has chaired sessions at five major National conferences. These include Lorne Genome, Epigenetics, Australasian Genome & Technologies Association (AGTA) and ComBio. She has also been invited to present at prestigious institution series such as the WEHI postgraduate lecture series (2015) and USC Grand Rounds (USA, 2010). She has been invited to join the organising committee of the flagship Australian Epigenetic Alliance (AEpiA) conferences, Epigenetics 2013 and 2015, was a advisory committee member for Epigenetics 2017 and sits on the scientific advisory board of AEpiA. She has been invited to Cancer Australia and NHMRC (Assistant Chair) grant review panels and was appointed co-convenor of the Tasmanian chapter of the Australian Society of Medical Research (ASMR) in 2017. She provides peer review expertise to the NHMRC for early career fellowships (2012-current) and project grants (2011-current) and to a number of international peer review journals.

View more on Dr Phillippa Taberlay in WARP

Expertise

  • Epigenomics
  • Epigenetics
  • Epigenetic Mechanisms
  • Chromatin
  • Molecular Biology
  • Next-Generation Sequencing
  • Assay Development
  • Genomics
  • Computational Biology
  • Development
  • Cancer
  • Alzheimer’s Disease

Research Themes

Phillippa’s research is aligns to the University’s research theme of Better Health, including the core strengths of genetics, neuroscience and applied mathematics. Phillippa’s research focuses on understanding how the epigenetic machinery controls fundamental biological processes; molecular circuits, fate, memory and the functionality of cells. She employs a systematic approach using a combination of molecular techniques as well as computational and mathematical modelling to answer her biological questions, which also aligns to the research theme Data, Knowledge & Decisions.

Collaboration

Phillippa is currently involved in projects involving researchers from Switzerland, U.S.A and Australia. With Dr Adele Woodhouse, Phillippa co-established an international collaboration with A/Prof Mark Robinson (IMLS, Switzerland), A/Prof Timothy Mercer (Garvan Institute of Medical Research and Altius Institute of Biomedical Sciences, Seattle, Washington) and Prof James Vickers (UTAS) to investigate the epigenomic mechanisms of ageing, and underlying onset and development of sporadic Alzheimer’s disease. She also collaborates with Dr Mate Biro (UNSW, Australia) and A/Prof Fabio Luciani (UNSW, Australia) to investigate epigenomic reprogramming during dynamic cancer metastases, and Dr Clare Stirzaker (Garvan Institute of Medical Research) and Prof Susan Clark (Garvan Institute of Medical Research) to study the epigenomics of prostate cancer.

At UTAS, Phillippa works closely with Dr Adele Holloway, A/Prof Alex Hewitt, Dr Tony Cook, Dr Guei-Sheung (Rick) Liu, A/Prof Joanne Dickinson, Dr Raj Eri, Dr Kate Brettingham-Moore and Dr Liesel FitzGerald in several exciting projects across the School of Medicine, Wicking Dementia Research and Education Centre, School of Health Sciences and the Menzies Research Institute for Medical Research.

Awards

  • 2016-2019 NHMRC Career Development Fellow
  • 2013-2016 Cancer Institute NSW Early-Career Development Fellow
  • 2012 L’Oréal for Women in Science Fellowship (shortlisted finalist)
  • 2008-2011 Norris Comprehensive Cancer Center Postdoctoral Research Fellow (USA)
  • 2009 Aspen Cancer Conference Fellow (Award) (USA)
  • 2004-2007 Japanangka Errol West Indigenous Postgraduate Research Scholarship
  • 2007 Jeanne Foster Scholarship (Award) (Cancer Council of Tasmania)
  • 2007 David Collins Leukaemia Foundation Scholarship (Award)
  • 2010 Outstanding Merit Award, Norris Comprehensive Cancer Center (USA)
  • 2009 Australian Department of Innovation, Industry & Regional Development Award
  • 2009 Benjamin F. Trump Award (USA)
  • 2008-current Several prizes for poster presentations at local and international conferences

Current projects

  • Long-range interactions and temporal regulation of the epigenome
  • The role of three-dimensional genome structures in normal and cancer cell biology
  • Understanding the role of nucleosomes in driving aberrant epigenetic signatures
  • Mapping epigenomic information in a three-dimensional cancer cell environment
  • Epigenetic regulation of chromatin remodeller proteins in cancer cells
  • Delineating epigenetic evolution in Alzheimer’s disease
  • Identifying alterations in epigenetic modifier complexes and telomere length in Alzheimer’s disease
  • Using environmental enrichment to understand epigenetic ageing

Fields of Research

  • Epigenetics (incl. Genome Methylation and Epigenomics) (060404)
  • Cancer Cell Biology (111201)
  • Bioinformatics (060102)

Research Objectives

  • Cancer and Related Disorders (920102)
  • Neurodegenerative Disorders Related to Ageing (920112)
  • Expanding Knowledge in the Agricultural and Veterinary Sciences (970107)

Publications

Phillippa has published her work in esteemed international journals such as Cell, PNAS, Cancer Cell and Genome Research. Her work has commanded considerable international attention.Her finding that so-called “junk DNA” allows cells to change phenotype was highlighted in “Cancer: New Insights for the Healthcare Professional 2012” and was selected by the editorial board of Cell as the sole video feature.Her research describing epigenetic “drivers” and “passengers” was named one of the Top Clinical Advances 2012 (ASCO) and was featured by Faculty of 1000, Nat. Rev. Cancer and specialist websites. Peers recognised her co-authored work on deciphering how stem cell factors control DNA and the 'order' of epigenetic events with a prestigious F1000 recommendation, while the development of NOMe-Seq (Nucleosome Occupancy and Methylation Sequencing), of which she performed assay establishment and optimisation, has been described as an “impressive” and “ingenious innovation”. NOMe-Seq was named as a Top 10 Innovation of 2013 and has since been commercialised.

Total publications

24

Highlighted publications

(6 outputs)
YearTypeCitationAltmetrics
2016Journal ArticleTaberlay PC, Achinger-Kawecka J, Lun ATL, Buske FA, Sabir K, et al., 'Three-dimensional disorganisation of the cancer genome occurs coincident with long range genetic and epigenetic alterations', Genome Research, 26 pp. 719-731. ISSN 1549-5469 (2016) [Refereed Article]

DOI: 10.1101/gr.201517.115 [eCite] [Details]

Citations: Scopus - 79Web of Science - 76

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2015Journal ArticleStatham AL, Taberlay PC, Kelly TC, Jones PA, Clark SJ, 'Genome-wide nucleosome occupancy and DNA methylation profiling of four human cell lines', Genomics Data, 3 pp. 94-96. ISSN 2213-5960 (2015) [Refereed Article]

DOI: 10.1016/j.gdata.2014.11.012 [eCite] [Details]

Citations: Scopus - 6Web of Science - 6

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2014Journal ArticleTaberlay PC, Stratham AL, Kelly TK, Clark SJ, Jones PA, 'Reconfiguration of Nucleosome Depleted Regions at Distal Regulatory Elements Accompanies DNA Methylation of Enhancers and Insulators in Cancer', Genome Research, 24 pp. 1421-1432. ISSN 1088-9051 (2014) [Refereed Article]

DOI: 10.1101/gr.163485.113 [eCite] [Details]

Citations: Scopus - 99Web of Science - 96

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2012Journal ArticleDe Carvalho DD, Sharma S, You JS, Su S-F, Taberlay PC, et al., 'DNA Methylation Screening Identifies Driver Epigenetic Events of Cancer Cell Survival', Cancer Cell, 21 pp. 655-667. ISSN 1535-6108 (2012) [Refereed Article]

DOI: 10.1016/j.ccr.2012.03.045 [eCite] [Details]

Citations: Scopus - 151Web of Science - 142

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2011Journal ArticleTaberlay PC, Kelly TK, Liu C-C, You JS, De Carvalho DD, et al., 'Polycomb-Repressed Genes Have Permissive Enhancers that Initiate Reprogramming', Cell, 147 pp. 1283-1294. ISSN 0092-8674 (2011) [Refereed Article]

DOI: 10.1016/j.cell.2011.10.040 [eCite] [Details]

Citations: Scopus - 120Web of Science - 114

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2011Journal ArticleYou JS, Kelly TK, De Carvalho DD, Taberlay PC, Liang G, et al., 'OCT4 establishes and maintains nucleosome-depleted regions that provide additional layers of epigenetic regulation of its target genes', Proceedings of the National Academy of Sciences, 108, (35) pp. 14497-14502. ISSN 0027-8424 (2011) [Refereed Article]

DOI: 10.1073/pnas.1111309108 [eCite] [Details]

Citations: Scopus - 81Web of Science - 79

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Journal Article

(19 outputs)
YearCitationAltmetrics
2019Dyer M, Phipps AJ, Mitew S, Taberlay PC, Woodhouse A, 'Age, but not amyloidosis, induced changes in global levels of histone modifications in susceptible and disease-resistant neurons in Alzheimer's disease model mice', Frontiers in Aging Neuroscience, 11 Article 68. ISSN 1663-4365 (2019) [Refereed Article]

DOI: 10.3389/fnagi.2019.00068 [eCite] [Details]

Co-authors: Phipps AJ; Woodhouse A

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2019Sutton LP, Jeffreys SA, Phillips JL, Taberlay PC, Holloway AF, et al., 'DNA methylation changes following DNA damage in prostate cancer cells', Epigenetics pp. 1-14. ISSN 1559-2294 (2019) [Refereed Article]

DOI: 10.1080/15592294.2019.1629231 [eCite] [Details]

Co-authors: Sutton LP; Jeffreys SA; Phillips JL; Holloway AF; Ambrose M; Young Arabella; Berry R; Brettingham-Moore KH

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2019Giles KA, Gould CM, Du Q, Skvortsova K, Song JZ, et al., 'Integrated epigenomic analysis stratifies chromatin remodellers into distinct functional groups', Epigenetics and Chromatin, 12, (1) pp. 1-19. ISSN 1756-8935 (2019) [Refereed Article]

DOI: 10.1186/s13072-019-0258-9 [eCite] [Details]

Citations: Scopus - 1Web of Science - 1

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2018Phillips JL, Taberlay PC, Woodworth AM, Hardy K, Brettingham-Moore KH, et al., 'Distinct mechanisms of regulation of the ITGA6 and ITGB4 genes by RUNX1 in myeloid cells', Journal of Cellular Physiology, 233, (4) pp. 3439-3453. ISSN 0021-9541 (2018) [Refereed Article]

DOI: 10.1002/jcp.26197 [eCite] [Details]

Citations: Scopus - 4Web of Science - 4

Co-authors: Phillips JL; Woodworth AM; Brettingham-Moore KH; Dickinson JL; Holloway AF

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2016Achinger-Kawecka J, Taberlay PC, Clark SJ, 'Alterations in three-dimensional organization of the cancer genome and epigenome', Cold Spring Harbor Symposia on Quantitative Biology, 81 pp. 41-51. ISSN 0091-7451 (2016) [Refereed Article]

DOI: 10.1101/sqb.2016.81.031013 [eCite] [Details]

Citations: Scopus - 6Web of Science - 5

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2016Phipps AJ, Vickers JC, Taberlay PC, Woodhouse A, 'Neurofilament-labeled pyramidal neurons and astrocytes are deficient in DNA methylation marks in Alzheimer's disease', Neurobiology of Aging, 45 pp. 30-42. ISSN 0197-4580 (2016) [Refereed Article]

DOI: 10.1016/j.neurobiolaging.2016.05.003 [eCite] [Details]

Citations: Scopus - 9Web of Science - 11

Co-authors: Phipps AJ; Vickers JC; Woodhouse A

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2016Skortsova K, Taberlay P, Clark SJ, Stirzaker C, 'Role of 5-Hydroxymethylation and TET enzymes in remodelling the epigenome', Experimental Medicine, 34, (10) pp. 1-9. ISSN 1791-9967 (2016) [Non Refereed Article]

[eCite] [Details]

2016Taberlay PC, Achinger-Kawecka J, Lun ATL, Buske FA, Sabir K, et al., 'Three-dimensional disorganisation of the cancer genome occurs coincident with long range genetic and epigenetic alterations', Genome Research, 26 pp. 719-731. ISSN 1549-5469 (2016) [Refereed Article]

DOI: 10.1101/gr.201517.115 [eCite] [Details]

Citations: Scopus - 79Web of Science - 76

Tweet

2015Brettingham-Moore KH, Taberlay PC, Holloway AF, 'Interplay between transcription factors and the epigenome: insight from the role of RUNX1 in leukemia', Frontiers in Immunology, 6 Article 499. ISSN 1664-3224 (2015) [Refereed Article]

DOI: 10.3389/fimmu.2015.00499 [eCite] [Details]

Citations: Scopus - 10Web of Science - 10

Co-authors: Brettingham-Moore KH; Holloway AF

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2015Brettingham-Moore KH, Taberlay PC, Holloway AF, 'Interplay between transcription factors and the epigenome: insight from the role of RUNX1 in leukemia', Frontiers in Immunology, 6 pp. 1-7. ISSN 1664-3224 (2015) [Refereed Article]

DOI: 10.3389/fimmu.2015.00499 [eCite] [Details]

Citations: Scopus - 10Web of Science - 10

Co-authors: Brettingham-Moore KH; Holloway AF

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2015Qadi A, Taberlay PC, Phillips JL, Young A, West AC, et al., 'The leukemia inhibitory factor receptor gene is a direct target of RUNX1', Journal of Cellular Biochemistry, 117, (1) pp. 49-58. ISSN 0730-2312 (2015) [Refereed Article]

DOI: 10.1002/jcb.25246 [eCite] [Details]

Citations: Scopus - 1Web of Science - 1

Co-authors: Phillips JL; Young A; West AC; Brettingham-Moore KH; Dickinson JL; Holloway AF

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2015Statham AL, Taberlay PC, Kelly TC, Jones PA, Clark SJ, 'Genome-wide nucleosome occupancy and DNA methylation profiling of four human cell lines', Genomics Data, 3 pp. 94-96. ISSN 2213-5960 (2015) [Refereed Article]

DOI: 10.1016/j.gdata.2014.11.012 [eCite] [Details]

Citations: Scopus - 6Web of Science - 6

Tweet

2014Taberlay PC, Stratham AL, Kelly TK, Clark SJ, Jones PA, 'Reconfiguration of Nucleosome Depleted Regions at Distal Regulatory Elements Accompanies DNA Methylation of Enhancers and Insulators in Cancer', Genome Research, 24 pp. 1421-1432. ISSN 1088-9051 (2014) [Refereed Article]

DOI: 10.1101/gr.163485.113 [eCite] [Details]

Citations: Scopus - 99Web of Science - 96

Tweet

2012De Carvalho DD, Sharma S, You JS, Su S-F, Taberlay PC, et al., 'DNA Methylation Screening Identifies Driver Epigenetic Events of Cancer Cell Survival', Cancer Cell, 21 pp. 655-667. ISSN 1535-6108 (2012) [Refereed Article]

DOI: 10.1016/j.ccr.2012.03.045 [eCite] [Details]

Citations: Scopus - 151Web of Science - 142

Tweet

2011Taberlay PC, Kelly TK, Liu C-C, You JS, De Carvalho DD, et al., 'Polycomb-Repressed Genes Have Permissive Enhancers that Initiate Reprogramming', Cell, 147 pp. 1283-1294. ISSN 0092-8674 (2011) [Refereed Article]

DOI: 10.1016/j.cell.2011.10.040 [eCite] [Details]

Citations: Scopus - 120Web of Science - 114

Tweet

2011You JS, Kelly TK, De Carvalho DD, Taberlay PC, Liang G, et al., 'OCT4 establishes and maintains nucleosome-depleted regions that provide additional layers of epigenetic regulation of its target genes', Proceedings of the National Academy of Sciences, 108, (35) pp. 14497-14502. ISSN 0027-8424 (2011) [Refereed Article]

DOI: 10.1073/pnas.1111309108 [eCite] [Details]

Citations: Scopus - 81Web of Science - 79

Tweet

2010Oakford PC, James SR, Qadi A, West AC, Ray SN, et al., 'Transcriptional and epigenetic regulation of the GM-CSF promoter by RUNX1', Leukemia Research, 34, (9) pp. 1203-1213. ISSN 0145-2126 (2010) [Refereed Article]

DOI: 10.1016/j.leukres.2010.03.029 [eCite] [Details]

Citations: Scopus - 8Web of Science - 8

Co-authors: West AC; Ray SN; Holloway AF

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2008Brettingham-Moore KH, Sprod OR, Chen X, Oakford PC, Shannon MF, et al., 'Determinants of a transcriptionally competent environment at the GM-CSF promoter', Nucleic Acids Research, 36, (8) pp. 2639-2653. ISSN 0305-1048 (2008) [Refereed Article]

DOI: 10.1093/nar/gkn117 [eCite] [Details]

Citations: Scopus - 16Web of Science - 14

Co-authors: Brettingham-Moore KH; Sprod OR; Holloway AF

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2007Holloway AF, Oakford PC, 'Targeting Epigentic Modifiers in Cancer', Current Medicinal Chemistry, 14, (24) pp. 2540-2547. ISSN 0929-8673 (2007) [Refereed Article]

DOI: 10.2174/092986707782023271 [eCite] [Details]

Citations: Scopus - 16Web of Science - 13

Co-authors: Holloway AF

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Chapter in Book

(2 outputs)
YearCitationAltmetrics
2018Giles KA, Taberlay PC, 'Mutations in Chromatin Remodeling Factors', Encyclopedia of Cancer 3rd Edition, Elsevier, G Pfeifer (ed), United States ISBN 9780128124840 (2018) [Other Book Chapter]

DOI: 10.1016/B978-0-12-801238-3.65225-X [eCite] [Details]

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2015Brettingham-Moore KH, Taberlay PC, 'Cancer Epigenetics', Drug Discovery in Cancer Epigenetics, Academic Press, G Egger & P Arimondo (ed), United Kingdom, pp. 41-62. ISBN 978-0128022085 (2015) [Research Book Chapter]

[eCite] [Details]

Co-authors: Brettingham-Moore KH

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Review

(2 outputs)
YearCitationAltmetrics
2014Skulte KA, Phan L, Clark SJ, Taberlay PC, 'Chromatin remodeler mutations in human cancers: epigenetic implications', Epigenomics, 6, (4) pp. 397-414. ISSN 1750-1911 (2014) [Substantial Review]

DOI: 10.2217/epi.14.37 [eCite] [Details]

Citations: Scopus - 16Web of Science - 15

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2014Stirzaker C, Taberlay PC, Satham AL, Clark SJ, 'Mining cancer methylomes: prospects and challenges', Trends in Genetics: Dna, Differentiation and Development, 30, (2) pp. 75-84. ISSN 0168-9525 (2014) [Substantial Review]

DOI: 10.1016/j.tig.2013.11.004 [eCite] [Details]

Citations: Scopus - 86Web of Science - 82

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Conference Publication

(1 outputs)
YearCitationAltmetrics
2005Oakford PC, Holloway AF, 'Regulation of gene expression by the RUNX-1 transcription factor', The Genome Conference, 13-17 Feb 2005, Victoria, pp. 108. (2005) [Conference Extract]

[eCite] [Details]

Co-authors: Holloway AF

Grants & Funding

Dr Taberlay has secured ~$4.1 million in competitive research funding since 2013. This includes an ARC Indigenous Discovery Grant (CIs Taberlay, Woodhouse, Vickers 2018–21; $460k); NHMRC Project Grant (CIs Clark, Taberlay 2013–15; $695k); Cure Cancer Australia Project Grant (as sole CI 2014–16 (1 of 16 awarded nationally); $200k); Judith Jan Mason and Harold Stannett Williams Memorial Foundation National Medical Program grant (CIs Taberlay, Woodhouse, Mercer 2015-16); Brain Foundation of Australia Research Gift (CIs Taberlay, Woodhouse, Robinson, Mercer 2017); Rebecca L. Cooper Foundation Grant (CIs Taberlay, Woodhouse 2017); Cancer Council Tasmania Research Grant (CIs Taberlay, Biro, Holloway, Brettingham-Moore, 2017); Cancer Institute NSW Career Development Fellowship (2013–16; $600k) and NHMRC CDF (2016–19; $420k) plus additional peer-reviewed seed funding for innovative research.

Funding Summary

Number of grants

22

Total funding

$6,514,003

Projects

Ageing matters: Chromatin remodelling in healthy ageing and disease. (2020 - 2024)$1,241,554
Description
Ageing is the single greatest risk factor for both cancers and dementias, indicating that the things we are exposed to over a lifetime can alter our disease risk. The epigenome lies at this interface it is dynamic and modifiable. For decades the field has sought to determine what epigenetic changes dysregulate gene promoters in cancer and how or why they occur. However, promoters do not act in isolation, DNA does not exist as a linear molecule inside cells and many questions remain. Foremost, it is increasingly apparent that epigenomic reprogramming is necessary during healthy aging and that deviations from this process underpin every disease affecting human health, including dementia and other non-cancerous pathologies. My research program will have an exceptional KNOWLEDGE impact by (1) defining the limits of epigenetic flexibility in healthy ageing and (2) understanding why and how the epigenome is reprogrammed, causing molecular damage that initiates and drives cancers and dementias. My complementary research themes address a deceptively simple question: How, why and what makes the epigenome so important? * BRG1-driven three-dimensional chromatin remodeling in cancer cells* Epigenetic evolution of neurons in sporadic Alzheimers disease* Positively modulating the ageing epigenome with environmental enrichment* Manipulating chromatin modifiers to recreate cancer epigenomes* Higher-order neuronal chromatin maps in healthy ageing and Alzheimer's diseaseThese projects leverage my expertise in sophisticated epigenomic assays in combination with advanced cell biology approaches in 2D and 3D cancer models, mouse models of ageing and Alzheimers disease, as well as human Alzheimers disease cases and healthy, aged individuals. By challenging currently accepted paradigms we will make the greatest knowledge breakthroughs, towards understanding how we can purposefully modulate the epigenome for future health, economic and social benefit.
Funding
National Health & Medical Research Council ($1,241,554)
Scheme
Fellowship-Investigator Grant
Administered By
University of Tasmania
Research Team
Taberlay PC
Period
2020 - 2024
Grant Reference
APP1176417
The impact of repeated DNA damage on the molecular profile of prostate cancer cells (2019)$23,295
Description
Many cancer patients receive fractionated/recurrent dosages of DNA damaging agents and there is some evidence that this may drive future treatment resistance and metastasis. This project will profile prostate cancer cells after repeated DNA damage via RNA-seq and EPIC arrays
Funding
Royal Hobart Hospital Research Foundation ($23,295)
Scheme
Grant-Project
Administered By
University of Tasmania
Research Team
Brettingham-Moore KH; Black Allison; Taberlay PC; Holloway AF
Year
2019
Delineating the epigenetic evolution of neurons in human sporadic Alzheimer's disease (2019 - 2021)$826,102
Description
Sporadic Alzheimer's disease (sAD) is not part of normal aging and we must determine how and why it occurs. The epigenome (meaning, 'above genes') ensures that our genes are expressed in the right cell type at the right time. Epigenetic defects are of great interest as they are reversible; but first, the epigenetic changes that characterise AD progression must be defined. Our overall aim is to identify how epigenetic programming is altered in the nerve cells that die in AD.
Funding
National Health & Medical Research Council ($826,102)
Scheme
Grant-Project
Administered By
University of Tasmania
Research Team
Taberlay PC; Woodhouse A; Robinson M; Mercer T
Period
2019 - 2021
Grant Reference
1161768
Deciphering the molecular basis of three-dimensional BRG1-driven chromatin remodelling in cancer cells (2019 - 2022)$969,187
Description
Our goal is to determine why DNA is packaged differently inside normal and cancer cells. We hypothesise that we can change the way DNA is packaged inside cancer cells so that we can force them to behave similarly to normal cells.
Funding
National Health & Medical Research Council ($969,187)
Scheme
Grant-Project
Administered By
University of Tasmania
Research Team
Taberlay PC; Jones P; Robinson M
Period
2019 - 2022
Grant Reference
1161985
A Clinical and Biospecimens Prostate Cancer Resource for Biomarker Research in Tasmania (2018)$22,146
Description
We propose to build upon the clinically-focused Prostate Cancer Outcomes Registry, Tasmania (PCOR-TAS) and collect matched biological samples to create a valuable resource for both clinicians and scientists. The availability of clinical and genetic data will allow important biomarker research into predicting prostate cancer outcomes and improving treatment strategies.
Funding
Royal Hobart Hospital Research Foundation ($22,146)
Scheme
Grant-Minor Project
Administered By
University of Tasmania
Research Team
Fitzgerald LM; Dickinson JL; Skala M; Stokes BC; Donovan S; Malley RC; Redwig F; Holloway AF; Taberlay PC
Year
2018
Turning back the clock on brain cell aging (2018 - 2021)$458,608
Description
This proposal aims to determine the role of fundamental epigenetic mechanisms in the process of aging. It combines the fields of epigenetics, neurosciences and mathematics to delineate the dynamics of DNA methylation and histone modification marking on the transcriptome during normal, healthy aging. This project will uniquely apply environmental enrichment to determine whether modulation of the epigenome underpins an improvement in cognitive function. Thus, whether an adult, rather than aged, epigenome can be maintained in neurons duringaging.
Funding
Australian Research Council ($458,608)
Scheme
Grant-Discovery Indigenous
Administered By
University of Tasmania
Research Team
Taberlay PC; Woodhouse A; Vickers JC
Period
2018 - 2021
Grant Reference
IN180100005
Identifying critical neuronal signatures of epigenetic modifier complexes of Alzheimer's disease initiation and progression (2017)$33,000
Description
Aging causes our cells to decline in both integrity and function. As such, the incidence of disorders that affect nerve cells, including Alzheimers disease (AD), increases with aging. In healthy cells, our genes are tightly regulated so that the correct combination of genes are switched on, or off, at the proper time to allow for learning and memory to occur. This is achieved by the addition or removal of small chemical residues associated with DNA, and the study of these processes is known as epigenetics. Epigenetic marks can change during aging, and diseases occur when this happens too quickly or in an uncontrolled way. Proper epigenetic control must be maintained during aging and we raise the possibility that epigenetic dysregulation plays an important role in AD progression. Surprising though, existing knowledge of the epigenetic alterations in AD is extremely limited, highlighting that new knowledge in this area is critical and that the timing of our study is significant. We present striking preliminary data revealing that epigenetic changes are occurring in AD and that they are affecting important gene regulatory regions. Our overall aim is to investigate whether the proteins in charge of regulating epigenetic processes behave abnormally in AD. At completion we will understand whether certain epigenetic signatures are associated with different stages in sporadic AD, and whether they differ between sporadic and familial AD. Ours is the only study currently measuring epigenetic changes specifically in nerve cells. These findings will significantly advance our understanding of the role of epigenetic dysregulation in AD and ss epigenetic defects are reversible, this study could also identify new clinical targets to improve the outcomes for people living with AD.
Funding
Brain Foundation ($33,000)
Scheme
Grant-Research
Administered By
University of Tasmania
Research Team
Taberlay PC; Woodhouse A; Robinson M; Mercer T
Year
2017
New geNOMeC maps of neuronal epigenetic changes in Alzheimer's disease (2017)$24,971
Description
Every cell in our body contains an identical genetic code; yet, for example, our heart and brain are very different. This is made possible by a process called epigenetics, which describes the addition and removal of small chemical marks above (epi) our DNA (genetics). Epigenetic marks carefully build layers on top of each other and when this happens properly, the right genes are expressed in the right cells at the right time and allow them to function as they should. However, there are no techniques to measure more than two epigenetic marks at the same time. Our overall goal is to address this deficit by developing a new technique that measures three epigenetic marks simultaneously (DNA methylation, histone modifications, nucleosomes). The benefit will be unlimited because it will be applicable to all normal and disease states, and all organisms. Furthermore, we will use this capability to determine whether epigenetic mistakes could explain why certain cells in the brain (neurons) are dysfunctional and die in Alzheimers disease, while other cells are resistant. This is a critical question in the field and our new data may unlock vital clues about the molecular etiology of this currently incurable disease.
Funding
Rebecca L Cooper Medical Research Foundation ($24,971)
Scheme
Grant
Administered By
University of Tasmania
Research Team
Taberlay PC; Woodhouse A
Year
2017
Mapping epigenomic information in a three-dimensional prostate cancer cell environment (2017)$20,990
Description
We lack a model that better replicates in vivo tumour development to study epigenomic mechanisms of prostate cancer. To date, epigenetic changes in cancer have been investigated in homogenous cell lines from two-dimensional laboratory cultures or end-point tumour samples (static) from patients. Without doubt these studies have provided great insight into epigenetic differences that distinguish cancer cells from normal cells. However, there is a glaring lack of information about dynamic and temporal changes to the epigenome and cell behaviour as the cells acquire invasive potential. This is not possible using currently available two-dimensional models and clinical samples. We will address this deficit by establishing a three-dimensional model of prostate cancer that allows us to map how epigenomes and cell behaviours change during cancer development.
Funding
Cancer Council of Tasmania ($20,990)
Scheme
Grant-Cancer Research
Administered By
University of Tasmania
Research Team
Taberlay PC; Brettingham-Moore KH; Holloway AF; Biro M
Year
2017
Developing CRISPR/Cas Library Screens for identifying Novel Cancer Therapies (2017)$63,845
Description
Our understanding of many cancers has improved dramatically over the past decade predominantly due to our ability to sequence entire genomes, at scale. Yet, we still require a better understanding of the underlying mechanisms that initiate and perpetuate cancers, as well as gene-based factors that initiate the transition from indolent to aggressive cancers with a propensity to metastasize. CRISPR/Cas is proving a robust, powerful and necessary tool in the laboratory that will undoubtedly underpin the next breakthrough in the field of cancer. As such, it is essential that we develop this capability at the University of Tasmania in a timely manner.The specific AIMS of this proposal are to:Aim 1: Establish CRISPR/Cas screening at the University of Tasmania as a tool to identify genesthat drive aggressive and metastatic cancers.Aim 2: Perform a genome-wide CRISPR/Cas negative selection (loss-of-function) screen toidentify genes essential for proliferation and survival, as well as metastatic behaviour.
Funding
University of Tasmania Foundation Inc ($63,845)
Scheme
Grant-Cancer Research
Administered By
University of Tasmania
Research Team
Taberlay PC; Hewitt A; Holloway AF; Liu G; Dickinson JL; Brettingham-Moore KH; Fitzgerald L; Eri RD; Cook AL
Year
2017
Molecular profiling of the post radiotherapy chromatin landscape in prostate cancer cells (2016)$33,000
Description
This project will investigate the basal and post radiotherapy epigenetic changes in prostate cancer cells with divergent response to radiotherapy (RT). It will validate methylation data obtained from illumina Infinium 450 beadchip arrays, profile histone modifications post RT and investigate DNA damage post RT in cells treated with inhibitors of epigenetic enzymes (DNMT and HDAC).
Funding
Cancer Council of Tasmania ($33,000)
Scheme
Grant-Cancer Research
Administered By
University of Tasmania
Research Team
Brettingham-Moore KH; Ambrose M; Holloway AF; Skala M; Taberlay PC
Year
2016
Chromatin Dynamics as a Driver of Disease Initiation and Development (2016 - 2019)$419,180
Funding
National Health & Medical Research Council ($419,180)
Scheme
Fellowship-Career Development
Administered By
University of Tasmania
Research Team
Taberlay PC
Period
2016 - 2019
Grant Reference
1109696
Determining the functional importance of global, BRG1-driven interactions in cancer cells (2016)$37,000
Description
Cancer initiation and progression is caused by a complex series of genetic and epigenetic changes. Such epigenetic changes drive atypical gene activity through altered patterns of DNA methylation, histone variants/modifications and the physical chromatin structure (eg. nucleosome positions). These epigenetic changes have been extensively characterised at gene promoters and are considered hallmarks of cancer cells. However, it is often overlooked that many promoters themselves are regulated by distal regulatory elements (eg. enhancers) that act by long-range looping mechanisms to facilitate communication across genome-scale distances. The extent or importance of the epigenetic changes that occur at enhancers in cancer cells has not been determined. Striking observations from my recent work 1 (Taberlay et al., Cell 2011)[CIA-P10911062] established the model on which this new proposal is based. Foremost, that enhancers with active epigenetic signatures regulate transcriptionally repressed promoters. We found that the purpose of this unexpected, divergent epigenetic combination at enhancer/promoter pairs was to ensure that epigenetic flexibility was retained, so that normal cells can respond to reprogramming signals. Importantly, we observed that cells are rendered resistant to reprogramming signals when an enhancer is abnormally epigenetically silenced in cancer cells. The underlying mechanisms, and the wider implications of enhancer epigenetic alterations in cancer is unknown.
Funding
Cancer Australia ($37,000)
Scheme
Grant-Priority-driven Collab. Cancer Research
Administered By
Garvan Institute of Medical Research
Research Team
Taberlay PC
Year
2016
Single-cell DNA Methylome Sequencing to detect epigenetic heterogeneity in aged pyramidal neurons (2016)$14,407
Description
Chemical and physical modification of DNA enables phenotypic variation within individuals built from a single genome. Thestudy of epigenetics has the potential to span the spectrum of biology, but has been somewhat limited to some fields (e.g. cancerand aging) or by virtue of the methods currently available to map epigenomes. DNA methylation is a major component of theepigenome and underpins normal development and survival. It is measured by whole genome bisulfite sequencing (WGBS), whichprovides information on the methylation status of DNA loci from the entire pools of cells sampled as a population; thus,knowledge regarding the cell-to-cell variation in epigenetic signatures is severely lacking. Single-cell WGBS experiments are atthe cutting edge of epigenetics research (Smallwood et al., 2014, Nature Methods, Farlik et al., 2015, Cell Reports) and will allowus to ascertain the heterogeneity in DNA methylation patterns from cell to cell. Our study will address a substantial gap in knowledge in the field by generating the first single-cell WGBS data from individual aged neurons. Pyramidal neurons are postmitotic long-lived cells with the ability to accrue epigenetic differences over time, thus, providing an ideal model to assess the heterogeneity in the DNA methylomes of individual cells in healthy aging.
Funding
University of Tasmania ($14,407)
Scheme
Grant-Research Enhancement (REGS)
Administered By
University of Tasmania
Research Team
Woodhouse A; Taberlay PC; Vickers JC
Year
2016
Charting epigenetic reprogramming in Alzheimer's disease mice (2015)$50,020
Description
Aging constitutes a time-dependent decline in cellular integrity and function. As we age, the incidence of neurodegenerative disorders, including Alzheimers disease (AD) increase. Ordinarily, the genome remains under exquisite control; epigenetic plasticity in neurons isimportant for continued learning and memory1,2 and is retained across lifespan3. Epigenetic mechanisms such as DNA methylation, and histone modifications are absolutely necessary for proper transcriptional output that underpins these normal cellular processes. Indeed, theimportance of epigenetics has now been well established in cancer field, yet other diseases have been largely overlooked.We hypothesize that epigenetic changes are hallmarks of Alzheimers disease.Here, we emphasize that proper epigenetic control must be maintained during aging and raise the possibility that epigenetic dysregulation plays an important role in AD progression. Striking observations from our preliminary study forms the basis of this new proposal. Foremost, epigenetic marks defining both enhancers (H3K4me1, H3K27Ac) and promoters (H3K4me3, H3K27me3) are lost from gene regulatory regions, revealing that epigenetic reprogramming does occur in AD. Existing knowledge of the epigenetic alterations in AD is extremely limited, highlighting that new knowledge in this area is critical and the timing of this work is highly significant.Our OVERALL AIM is to determine the repertoire of epigenetic aberrations associated with Alzheimers disease and to test whether the development of disease is underpinned by an abnormal epigenetic program.Our Overall Aim will be addressed by:1) Generating maps of activating and repressive epigenetic marks across a time course that encompasses pre-disease, disease onset and late disease stages in a mouse model of AD.2) Identifing the spatial epigenetic changes that occur in distinct cell types across a time course of disease progression in AD mice.At completion we will understand whether distinct epigenetic signatures are associated with different stages in disease progression in AD, and if epigenetic alterations are cell typespecific or dependent on proximity to AD pathology. These findings will significantly advance our understanding of the role of pigenetic dysregulation in AD and could identifying new clinical targets to improve the outcomes for AD patients.
Funding
The Mason Foundation ($50,020)
Scheme
Grant-Judith Jane Mason & Harold Stannett Williams
Administered By
Garvan Institute of Medical Research
Research Team
Taberlay PC; Woodhouse A; Mercer T; Phipps AJ
Year
2015
BRG1-driven interactions in cancer cells. (2014 - 2017)$106,176
Funding
University of New South Wales ($106,176)
Scheme
Australian Postgraduate Award (APA)
Administered By
Garvan Institute of Medical Research
Research Team
Giles Katherine A; Taberlay Phillippa C; Clark Susan J
Period
2014 - 2017
Determining the functional importance of global, BRG1-driven interactions in cancer cells. (2014 - 2015)$199,298
Funding
Cancer Australia (Cure Cancer Australia Foundation) ($199,298)
Scheme
Project Grant
Administered By
Garvan Institute of Medical Research
Research Team
Taberlay Phillippa
Period
2014 - 2015
Assessing the role of DNA loops in cancer cells (2013)$693,374
Funding
Young Garvan Foundation ($693,374)
Scheme
Special Initiative Grant
Administered By
Garvan Institute of Medical Research
Research Team
Taberlay Phillippa
Year
2013
Beyond Traditional Gene Boundaries: Understanding the importance of enhancer epigenetic reprogramming and atypical long-range interactions in cancer cells. (2013 - 2015)$693,374
Funding
NHMRC ($693,374)
Scheme
Project Grant
Administered By
Garvan Institute of Medical Research
Research Team
Clark Susan J; Taberlay Phillippa C
Period
2013 - 2015
De-looping DNA loops using epigenetic cancer therapies. (2013 - 2015)$582,876
Funding
Cancer Institute NSW ($582,876)
Scheme
Fellowship
Administered By
Garvan Institute of Medical Research
Research Team
Taberlay Phillippa
Period
2013 - 2015
EMBO Conference on Chromatin and Epigenetics attendance (2007)$1,200
Funding
Cancer Council of Tasmania ($1,200)
Scheme
Grant-Travel
Administered By
University of Tasmania
Research Team
Holloway AF; Taberlay PC
Year
2007
Philippa Oakford: Epigenetics 2007 Australian Scientific Conference (2007)$400
Funding
David Collins Leukaemia Foundation ($400)
Scheme
Award-Professional Development
Administered By
University of Tasmania
Research Team
Holloway AF; Taberlay PC
Year
2007

Research Supervision

Phillippa currently supervises PhD students as primary (4) and co-supervisor (3). She has supervised Honours (first class and University medal), Masters (research) and PhD scholars to completion, and her students have all received highly competitive scholarships to complete their higher degrees at University of Tasmania, University of New South Wales, Sydney and Cambridge University, U.K. Phillippa is also involved in formal mentoring programs for students (e.g. “Life after a PhD”) and postdocs (e.g. “Effective Networking”).

Current

4

Current

DegreeTitleCommenced
PhDDNA Methylation and Histone Modification Dynamics in Neurons in Aging and Alzheimers Disease2016
PhDUnderstanding the Fundamental Role of Nucleosomes in Driving Aberrant Epigenetic Signatures2016
PhDDetermining the Epigenetic Regulation of SMARCA4 and ARID1A in Prostate Cancer2018
PhDIdentifying Critical Neuronal Signatures of Epigenetic Modifier Complexes and Telomere Length Alterations in Human Alzheimers Disease2018