Professor Adrian Bracken
Professor Of, Genetics
Biography
In 2021, I was elected an EMBO Member for outstanding achievement in the life sciences. My lab has made several seminal discoveries in the field of cancer epigenetics. In particular, we provided key contributions to the understanding of the molecular mechanisms of how Polycomb group proteins regulate cell-fate decisions in stem cells and in cancer. For example, in 2018, my lab discovered a new family of vertebrate specific Polycomb group proteins, called PALI1 and PALI2, that link nuclear receptor signalling and chromatin biology (Conway et al., Molecular Cell) and we are exploring how different Polycomb Repressive complexes (PRC2.1 and PRC2.2) interplay to direct deposition of the H3K27me3 epigenetic modification (Healy et al., 2019 and Glancy et al., 2023; Molecular Cell). My lab recently studied an incurable childhood cancer called 'H3-K27M-mutant diffuse midline glioma' and demonstrated that EZH2 inhibitor drugs are a mechanistically anchored treatment strategy, based on modelling the consequences of the H3-K27M cancer causing gene on the underlying biology (Brien et al., Nature Genetics, 2021). My lab is also focused on genetic predisposition to cancer and we are using our expertise in chromatin biology to explore the contribution of regulatory elements in the 'non-coding genome'. Additionally, several exciting ongoing projects in the lab are studying the roles of chromatin regulators in developmental disorders and cancer.
Publications and Further Research Outputs
Peer-Reviewed Publications
Bracken, A.P. and Pasini, D. and Capra, M. and Prosperini, E. and Colli, E. and Helin, K., Correction to: EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer (The EMBO Journal, (2003), 22, 20, (5323-5335), 10.1093/emboj/cdg542), EMBO Journal, 43, (5), 2024, p886
Bracken, A.P. and Kleine-Kohlbrecher, D. and Dietrich, N. and Pasini, D. and Gargiulo, G. and Beekman, C. and Theilgaard-Mönch, K. and Minucci, S. and Porse, B.T. and Marine, J.-C. and Hansen, K.H. and Helin, K., Corrigendum: The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells, Genes & development, 37, (17-18), 2023, p861
Glancy E, Wang C, Tuck E, Healy E, Amato S, Neikes HK, Mariani A, Mucha M, Vermeulen M, Pasini D, Bracken AP, PRC2.1- and PRC2.2-specific accessory proteins drive recruitment of different forms of canonical PRC1, MOLECULAR CELL, 2023
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
Glancy, E. and Ciferri, C. and Bracken, A.P., Structural basis for PRC2 engagement with chromatin, Current Opinion in Structural Biology, 67, 2020, p135-144
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
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
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
Deevy O and Bracken AP., PRC2 functions in development and congenital disorders, Development, 146, (19), 2019, pdev181354
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
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
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
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
Unraveling the Roles of Canonical and Noncanonical PRC1 Complexes. in, editor(s)Vincenzo Pirrotta , Polycomb Group Proteins, 2017, pp57-80 , [Conway, EM., Bracken, AP.]
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
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
Brien GL, Bracken AP., The PCL1-p53 axis promotes cellular quiescence., Cell Cycle, 15, (3), 2016, p305-306
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
Aloraifi, F. and Alshehhi, M. and McDevitt, T. and Cody, N. and Meany, M. and O'Doherty, A. and Quinn, C.M. and Green, A.J. and Bracken, A. and Geraghty, J.G., Phenotypic analysis of familial breast cancer: Comparison of BRCAx tumors with BRCA1 - BRCA2-carriers and non-familial breast cancer, European Journal of Surgical Oncology, 41, (5), 2015, p641-646
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
Conway E, Healy E, Bracken AP., PRC2 mediated H3K27 methylations in cellular identity and cancer., Current Opinion in Cell Biology, 37, 2015, p42-48
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
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
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
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
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
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
Turner, SA and Bracken AP., A "Complex" Issue: Deciphering the Role of Variant PRC1 in ESCs., Cell Stem Cell, 12, (2), 2013, p145 - 146
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
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, p1273-81
Lanigan F, Geraghty JG, Bracken AP., Transcriptional regulation of cellular senescence., Oncogene, 30, (26), 2011, p2901-2911
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
Bracken AP, Helin K., Polycomb group proteins: navigators of lineage pathways led astray in cancer, Nature Reviews Cancer, 9, (11), 2009, p773 - 784
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
Hansen, K.H. and Bracken, A.P. and Pasini, D. and Dietrich, N. and Gehani, S.S. and Monrad, A. and Rappsilber, J. and Lerdrup, M. and Helin, K., Erratum: A model for transmission of the H3K27me3 epigenetic mark (Nature Cell Biology (2008) vol. 10 (1291-1300)), Nature Cell Biology, 10, (12), 2008, p1484
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
Hansen, K.H. and Bracken, A.P. and Pasini, D. and Dietrich, N. and Gehani, S.S. and Monrad, A. and Rappsilber, J. and Lerdrup, M. and Helin, K., Erratum: A model for transmission of the H3K27me3 epigenetic mark (Nature Cell Biology (2008) vol. 10 (1291-1300)), Nature Cell Biology, 10, (11), 2008
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
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
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
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
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
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
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
Bracken AP, Ciro M, Cocito A, Helin K., E2F target genes: unraveling the biology., Trends in Biochemical Sciences, 29, (8), 2004, p409-417
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
Pasini, D., Bracken, AP., Helin, K., Polycomb group proteins in cell cycle progression and cancer., Cell Cycle, 3, (4), 2004, p396-400
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
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
Ciro M, Bracken AP, Helin K., Profiling cancer., Current Opinion in Cell Biology, 15, (2), 2003, p213-20
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
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
Non-Peer-Reviewed Publications
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
(ed.), Anticancer innovative therapy: Highlights from the ninth annual meeting, Cytokine Growth Factor Rev., Milan, Italy., 51, January, 2019, 2020, 1 - 9 p
Brien GL, Bracken AP., The 3D Genome: EZH2 Comes into the Fold., Trends in Molecular Medicine, 25, (5), 2019, p362 - 365
Streubel G, Bracken AP., MED23: a new Mediator of H2B monoubiquitylation., The EMBO Journal, 34, (23), 2015, p2863-2864
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
Turner SA, Bracken AP., A "complex" issue: deciphering the role of variant PRC1 in ESCs., Cell Stem Cell, 12, (2), 2013, p145-146
Research Expertise
Recognition
Awards and Honours
Elected an EMBO Member for outstanding achievement in the life sciences (Nominated by Nobel Prize Winner Thomas Cech).
Irish Research Council Advanced Laureate Awardee
Elected Fellow of Trinity College Dublin (FTCD)
EUROLIFE Distinguished Lecture Prize Awardee