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Dr. Adrian Bracken
Assoc Prof in Medical Molecular Genetics, Genetics

Biography

The Bracken lab has made multiple important contributions understanding of the molecular mechanisms of how Polycomb group proteins regulate cell-fate decisions and cancer. Recently, they discovered a new family of vertebrate specific proteins that link nuclear receptor signalling and chromatin biology (Conway et al., Molecular Cell, 2018) and explored how different Polycomb complexes interplay to direct deposition of the H3K27me3 modification (Healy et al., Molecular Cell, 2019). The lab recently studied a devastating childhood cancer called 'H3-K27M-mutant diffuse midline glioma' and proposed a treatment strategy based on understanding the consequences of the oncogene on the underlying chromatin state (Brien et al., Nature Genetics, 2021). The lab is also focused on genetic predisposition to cancer and are using their expertise in chromatin biology to explore the contribution of the 'non-coding genome'. Several exciting ongoing projects in the lab are studying the roles of chromatin regulators in developmental disorders and cancers.

Publications and Further Research Outputs

Peer-Reviewed Publications

Glancy, E. and Ciferri, C. and Bracken, A.P., Structural basis for PRC2 engagement with chromatin, Current Opinion in Structural Biology, 67, 2021, p135-144 Journal Article, 2021 TARA - Full Text DOI

Brien GL, Bressan RB, Monger C, Gannon D, Lagan E, Doherty AM, Healy E, Neikes H, Fitzpatrick DJ, Deevy O, Grant V, Marqués-Torrejón MA, Alfazema N, Pollard SM, Bracken AP., Simultaneous disruption of PRC2 and enhancer function underlies histone H3.3-K27M oncogenic activity in human hindbrain neural stem cells., Nature Genetics, 53, (8), 2021, p1221 - 1232 Journal Article, 2021

Lanigan F, Gallagher WM and Bracken AP., 'A method of predicting risk of recurrence of cancer', TCD and UCD, US 10,557,175, 2020, Jointly owned by TCD and UCD Patent, 2020 URL

Bracken AP, Brien GL and Verrijzer CP., Dangerous Liaisons: Interplay between SWI/SNF, NuRD and Polycomb in Chromatin Regulation and Cancer. , Genes & Development, 33, 2019, p1 - 24 Journal Article, 2019 TARA - Full Text DOI

Healy E, Mucha M, Glancy E, Fitzpatrick DJ, Conway E, Neikes HK, Monger C, Van Mierlo G, Baltissen MP, Koseki Y, Vermeulen M, Koseki H, and Bracken AP. , PRC2.1 and PRC2.2 synergize to co-ordinate H3K27 tri-methylation, Molecular Cell, 2019, p437-452.e6 Journal Article, 2019 DOI

Lanigan F, Gallagher WM and Bracken AP., 'A method of predicting risk of recurrence of cancer,', TCD and UCD, EP3194621, 2019, Jointly owned by TCD and UCD Patent, 2019 URL

Deevy O and Bracken AP., PRC2 functions in development and congenital disorders, Development, 146, (19), 2019, pdev181354 Journal Article, 2019 TARA - Full Text DOI

Streubel G, Watson A, Jammula SG, Scelfo A, Fitzpatrick DJ, Oliviero G, McCole R, Conway E, Glancy E, Negri GL, Dillon E, Wynne K, Pasini D, Krogan NJ, Bracken AP*, Cagney G*. (* Equal last authors)., The H3K36me2 Methyltransferase Nsd1 Demarcates PRC2-Mediated H3K27me2 and H3K27me3 Domains in Embryonic Stem Cells., Molecular Cell, 70, (2), 2018, p371-379 Journal Article, 2018 DOI

Conway E, Jerman E, Healy E, Ito S, Holoch D, Oliviero G, Deevy O, Glancy E, Fitzpatrick DJ, Mucha M, Watson A, Rice AM, Chammas P, Huang C, Bracken AP., A Family of Vertebrate-Specific Polycombs Encoded by the LCOR/LCORL Genes Balance PRC2 Subtype Activities., Molecular Cell, 70, (3), 2018, p408-421 Journal Article, 2018 TARA - Full Text DOI

Unraveling the Roles of Canonical and Noncanonical PRC1 Complexes. in, editor(s)Vincenzo Pirrotta , Polycomb Group Proteins, 2017, pp57-80 , [Conway, EM., Bracken, AP.] Book Chapter, 2017 DOI

Erceg J, Pakozdi T, Marco-Ferreres R, Ghavi-Helm Y, Girardot C, Bracken AP, Furlong EE., Dual functionality of cis-regulatory elements as developmental enhancers and Polycomb response elements., Genes & Development, 31, (6), 2017, p590-602 Journal Article, 2017 DOI

Streubel, G., Fitzpatrick, Streubel G, Fitzpatrick DJ, Oliviero G, Scelfo A, Moran B, Das S, Munawar N, Watson A, Wynne K, Negri GL, Dillon ET, Jammula S, Hokamp K, O'Connor DP, Pasini D, Cagney G, Bracken AP., Fam60a defines a variant Sin3a-Hdac complex in embryonic stem cells required for self-renewal, EMBO Journal, 36, 2017, p2216 - 2232 Journal Article, 2017 DOI

Brien GL, Bracken AP., The PCL1-p53 axis promotes cellular quiescence., Cell Cycle, 15, (3), 2016, p305-306 Journal Article, 2016 DOI

Oliviero, G., Brien, G.L., Waston, A., Streubel, G., Jerman, E., Andrews, D., Doyle, B., Munawar, N., Wynne, K., Crean, J., Bracken, A.P., Cagney, G., Dynamic protein interactions of the polycomb repressive complex 2 during differentiation of pluripotent cells., Molecular and Cellular Proteomics, 15, (11), 2016, p3450-3460 Journal Article, 2016 DOI

Brien GL, Healy E, Jerman E, Conway E, Fadda E, O'Donovan D, Krivtsov AV, Rice AM, Kearney CJ, Flaus A, McDade SS, Martin SJ, McLysaght A, O'Connell DJ, Armstrong SA, Bracken AP, A chromatin-independent role of Polycomb-like 1 to stabilize p53 and promote cellular quiescence., Genes & Development, 29, (21), 2015, p2231-43 Journal Article, 2015 DOI TARA - Full Text

Aloraifi, F., McCartan, D., McDevitt, T., Green, A.J., Bracken, A., Geraghty, J., Protein-truncating variants in moderate-risk breast cancer susceptibility genes: A meta-analysis of high-risk case-control screening studies., Cancer Genetics, 208, (9), 2015, p455-463 Journal Article, 2015 DOI

Aloraifi F, McDevitt T, Martiniano R, McGreevy J, McLaughlin R, Egan CM, Cody N, Meany M, Kenny E, Green AJ, Bradley DG, Geraghty JG, Bracken AP., Detection of novel germline mutations for breast cancer in non-BRCA1/2 families., FEBS J., 282, (17), 2015, p3424 - 3437 Journal Article, 2015 DOI

Oliviero G, Munawar N, Watson A, Streubel G, Manning G, Bardwell V, Bracken AP, Cagney G, The variant Polycomb Repressor Complex 1 component PCGF1 interacts with a pluripotency sub-network that includes DPPA4, a regulator of embryogenesis., Scientific Reports, 5, 2015, p18388 Journal Article, 2015 TARA - Full Text DOI

Conway E, Healy E, Bracken AP., PRC2 mediated H3K27 methylations in cellular identity and cancer., Current Opinion in Cell Biology, 37, 2015, p42-48 Journal Article, 2015 DOI

Aloraifi F, Alshehhi M, McDevitt T, Cody N, Meany M., O'Doherty A, Quinn CM, Green AJ, Bracken A, Geraghty JG, Comparison of BRCAx tumors with BRCA1 - BRCA2-carriers and non-familial breast cancer., EJSO, 41, (5), 2015, p641-646 Journal Article, 2015 TARA - Full Text DOI

Lanigan F, Brien GL, Fan Y, Madden SF, Jerman E, Maratha A, Aloraifi F, Hokamp K, Dunne EJ, Lohan AJ, Flanagan L, Garbe JC, Stampfer MR, Fridberg M, Jirstrom K, Quinn CM, Loftus B, Gallagher WM, Geraghty J, Bracken AP., Delineating transcriptional networks of prognostic gene signatures refines treatment recommendations for lymph node-negative breast cancer patients., FEBS J, 282, (18), 2015, p3455 - 3473 Journal Article, 2015 DOI

Munawar, N., Olivero, G., Jerman, E., Doyle, B., Streubel, G., Wynne, K., Bracken, A., Cagney, G., Native gel analysis of macromolecular protein complexes in cultured mammalian cells., Proteomics, 15, (21), 2015, p3603-3612 Journal Article, 2015 DOI

Egan CM, Nyman U, Skotte J, Streubel G, Turner S, O'Connell DJ, Rraklli V, Dolan MJ, Chadderton N, Hansen K, Farrar GJ, Helin K, Holmberg J, Bracken AP., CHD5 is required for neurogenesis and has a dual role in facilitating gene expression and polycomb gene repression, Developmental Cell, 26, (3), 2013, p223-236 Journal Article, 2013 TARA - Full Text DOI

Turner, SA and Bracken AP., A "Complex" Issue: Deciphering the Role of Variant PRC1 in ESCs., Cell Stem Cell, 12, (2), 2013, p145 - 146 Journal Article, 2013 TARA - Full Text URL DOI

Lisa A Mielke , Sarah A Jones, Mathilde Raverdeau, Rowan Higgs, Anna Stefanska, Joanna R Groom, Alicja Misiak, Lara S Dungan, Caroline E Sutton, Gundula Streubel, Adrian P Bracken, Kingston H G Mills, Retinoic Acid Expression Associates With Enhanced IL-22 Production by γδ T Cells and Innate Lymphoid Cells and Attenuation of Intestinal Inflammation, Journal of Experimental Medicine, 10, (6), 2013, p1117-24 Journal Article, 2013

Brien GL, Gambero G, O'Connell DJ, Jerman E, Turner SA, Egan CM, Dunne EJ, Jurgens MC, Wynne K, Piao L, Lohan AJ, Ferguson N, Shi X, Sinha KM, Loftus BJ, Cagney G, Bracken AP, Polycomb PHF19 binds H3K36me3 and recruits PRC2 and demethylase NO66 to embryonic stem cell genes during differentiation, Nature Structural & Molecular Biology, 19, (12), 2012, p1273-1281 Journal Article, 2012 URL DOI

Lanigan F, Geraghty JG, Bracken AP., Transcriptional regulation of cellular senescence., Oncogene, 30, (26), 2011, p2901-2911 Journal Article, 2011 DOI

Bracken AP, Helin K., Polycomb group proteins: navigators of lineage pathways led astray in cancer, Nature Reviews Cancer, 9, (11), 2009, p773 - 784 Journal Article, 2009 DOI TARA - Full Text

Brien GL, Bracken AP., Transcriptomics: Unravelling the biology of transcription factors and chromatin remodelers during development and differentiation, Seminars in Cell and Developmental Biology, 20, (7), 2009, p835 - 841 Journal Article, 2009 DOI TARA - Full Text

Pasini D, Bracken AP, Agger K, Christensen J, Hansen K, Cloos PA, Helin K., Regulation of stem cell differentiation by histone methyltransferases and demethylases., Cold Spring Harbor Symposia on Quantitative Biology, 73, 2008, p253-263 Journal Article, 2008 DOI

Krivtsov AV, Feng Z, Lemieux ME, Faber J, Vempati S, Sinha AU, Xia X, Jesneck J, Bracken AP, Silverman LB, Kutok JL, Kung AL, Armstrong SA., H3K79 methylation profiles define murine and human MLL-AF4 leukemias., Cancer Cell, 14, (5), 2008, p355-368 Journal Article, 2008 DOI

Hansen KH, Bracken AP, Pasini D, Dietrich N, Gehani SS, Monrad A, Rappsilber J, Lerdrup M, Helin K., A model for transmission of the H3K27me3 epigenetic mark., Nature Cell Biology, 10, (11), 2008, p1291-1300 Journal Article, 2008 DOI

Pasini, D., Bracken, AP., Hansen, JB., Capillo, M., Helin, K., The polycomb group protein Suz12 is required for embryonic stem cell differentiation., Molecular and Cellular Biology, 27, (10), 2007, p3769-3779 Journal Article, 2007 DOI

Bracken AP, Kleine-Kohlbrecher D, Dietrich N, Pasini D, Gargiulo G, Beekman C, Theilgaard-Mönch K, Minucci S, Porse BT, Marine JC, Hansen KH and Helin K., The Polycomb Group Proteins Bind Throughout the INK4A-ARF locus and are Disassociated in Senescent Cells., Genes and Development, 21, (5), 2007, p525 - 530 Journal Article, 2007 DOI

Del Arroyo, AG., El Messaoudi, S., Clark, P.A., James, M., Stott, F., Bracken, A., Helin, K., Peters, G., E2F-dependent induction of p14ARF during cell cycle re-entry in human T cells., Cell Cycle, 6, (21), 2007, p2697-2705 Journal Article, 2007 DOI

Dietrich N, Bracken AP, Trinh E, Schjerling CK, Koseki H, Rappsilber J, Helin K, Hansen KH., Bypass of senescence by the polycomb group protein CBX8 through direct binding to the INK4A-ARF locus., The EMBO Journal, 26, (6), 2007, p1637-1648 Journal Article, 2007 DOI

Bracken AP, Dietrich N, Pasini D, Hansen KH and Helin K, Genome-wide Mapping of Polycomb Target Genes Unravels Their Roles in Cell Fate Transitions., Genes and Development, 20, (9), 2006, p1123 - 1136 Journal Article, 2006 DOI TARA - Full Text

Christensen, J., Cloos, P., Toftegaard, U., Klinkenberg, D., Bracken, AP., Trinh, E., Heeran, M., Di Stefano L, Helin, K., Characterization of E2F8, a novel E2F-like cell-cycle regulated repressor of E2F-activated transcription, Nucleic Acids Research , 44, (17), 2005, p5458-5470 Journal Article, 2005 DOI TARA - Full Text

Pasini, D., Bracken, AP., Helin, K., Polycomb group proteins in cell cycle progression and cancer., Cell Cycle, 3, (4), 2004, p396-400 Journal Article, 2004

Bracken AP, Ciro M, Cocito A, Helin K., E2F target genes: unraveling the biology., Trends in Biochemical Sciences, 29, (8), 2004, p409-417 Journal Article, 2004 DOI

Pasini D, Bracken AP, Jensen MR, Lazzerini Denchi E, Helin K., Suz12 is essential for mouse development and for EZH2 histone methyltransferase activity., The EMBO Journal, 23, (20), 2004, p4061-4071 Journal Article, 2004 DOI

Bracken AP, Pasini D, Capra M, Prosperini E, Colli E, Helin K., EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer., The EMBO Journal, 22, (20), 2003, p5323-5335 Journal Article, 2003 DOI

Ciro M, Bracken AP, Helin K., Profiling cancer., Current Opinion in Cell Biology, 15, (2), 2003, p213-20 Journal Article, 2003 DOI

Gao, G., Bracken, AP., Burkard, K., Pasini, D., Classon, M., Attwooll, C., Sagara, M., Imai, T., Helin, K., Zhao, J., NPAT expression is regulated by E2F and is essential for cell cycle progression., Molecular and Cellular Biology, 23, (8), 2003, p2821-2833 Journal Article, 2003 DOI

Müller H, Bracken AP, Vernell R, Moroni MC, Christians F, Grassilli E, Prosperini E, Vigo E, Oliner JD, Helin K., E2Fs regulate the expression of genes involved in differentiation, development, proliferation, and apoptosis., Genes & Development, 15, (3), 2001, p267-285 Journal Article, 2001 DOI

Bracken A. and U. Bond, Reassembly and protection of small nuclear ribonucleoprotein particles by heat shock proteins in yeast cells, RNA, 5, 1999, p1586 - 1596 Journal Article, 1999 URL

Non-Peer-Reviewed Publications

(ed.), Anticancer innovative therapy: Highlights from the ninth annual meeting, Cytokine Growth Factor Rev., Milan, Italy., 51, January, 2019, 2020, 1 - 9 p Proceedings of a Conference, 2020

Healy E, Bracken AP., If You Like It Then You Shoulda Put Two "RINGs" on It: Delineating the Roles of vPRC1 and cPRC1, Molecular Cell, 77, (4), 2020, p685-687 Journal Article, 2020

Brien GL, Bracken AP., The 3D Genome: EZH2 Comes into the Fold., Trends in Molecular Medicine, 25, (5), 2019, p362 - 365 Journal Article, 2019 DOI

Streubel G, Bracken AP., MED23: a new Mediator of H2B monoubiquitylation., The EMBO Journal, 34, (23), 2015, p2863-2864 Journal Article, 2015 DOI

Benitah, S.A., Bracken, A., Dou, Y., Huangfu, D., Ivanova, N., Koseki, H., Laurent, L., Lim, D.A., Meshorer, E., Pombo, A., Sander, M., Xu, G.L., Stem cell epigenetics: Looking forward, Cell Stem Cell, 14, (6), 2014, p706-709 Journal Article, 2014 DOI

Turner SA, Bracken AP., A "complex" issue: deciphering the role of variant PRC1 in ESCs., Cell Stem Cell, 12, (2), 2013, p145-146 Journal Article, 2013 DOI

Research Expertise

Keywords

Cancer Genetics; Cellular identity; Chromatin biology; Epigenetics; Gene expression control; Polycomb proteins; Stem Cell Biology; The EZH2 oncogene

Recognition

Awards and Honours

Elected an EMBO Member for outstanding achievement in the life sciences. June 2021

Irish Research Council Advanced Laureate Awardee 2019-2023

Elected Fellow of Trinity College Dublin (FTCD) 2018-

Science Foundation Ireland Principal Investigator (IvP) Awardee 2017-2022

EUROLIFE Distinguished Lecture Prize Awardee 2016

Science Foundation Ireland 'Principal Investigator Career Advancement' (PICA) Awardee 2010-2015