Selected research publications

Shown here are some of the recent outstanding publications which highlight significant advances made by researchers in our institute.

Lancet 395:1268-1277 (2020). Birtle A, M Johnson, J Chester, R Jones, D Dolling, RT Bryan, . . . E Hall. Adjuvant chemotherapy in upper tract urothelial carcinoma (the POUT trial): a phase 3, open-label, randomised controlled trial.

J Clin Oncol:JCO2001933 (2020).Glasbey JC, A Bhangu and COVID Surg Collaborative. Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

EMBO J:e105220 (2020). Bevington SL, P Keane, JK Soley, S Tauch, DW Gajdasik, R Fiancette, . . . PN Cockerill. IL-2/IL-7-inducible factors pioneer the path to T cell differentiation in advance of lineage-defining factors.

Lancet 395:417-426 (2020). Bhangu A and Reinforcement of Closure of Stoma Site (ROCSS) Collaborative and West Midlands Research Collaborative. Prophylactic biological mesh reinforcement versus standard closure of stoma site (ROCSS): a multicentre, randomised controlled trial

Cell Rep 31:107748 (2020). Bevington SL, STH Ng, GJ Britton, P Keane, DC Wraith and PN Cockerill. Chromatin Priming Renders T Cell Tolerance-Associated Genes Sensitive to Activation below the Signaling Threshold for Immune Response Genes. Find out more: Birmingham scientists 're-train' immune system to prevent attack of healthy cells in new UK study into autoimmune diseases.

Lancet Child Adolesc Health 4:271-280 (2020). Bhangu A and Rift Study Group on behalf of the West Midlands Research Collaborative. Appendicitis risk prediction models in children presenting with right iliac fossa pain (RIFT study): a prospective, multicentre validation study. Find out more: Urgent improvements needed in the care of children with suspected appendicitis - study

Lancet 396:27-38 (2020). Bhangu A and COVIDSurg Collaborative. Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study. Find out more: COVID-19 patients who undergo surgery are at increased risk of postoperative death – global study

Cancer Cell 38:306-307 (2020). Lee LYW, T Hill, O Topping, M Tilby, M Baker, J Greig, . . . UKBCCC- Project. Utility of COVID-19 Screening in Cancer Patients.

Lancet Oncol 21:1309-1316 (2020). Lee LYW, JB Cazier, T Starkey, SEW Briggs, R Arnold, V Bisht, . . . UKCCMP Team. COVID-19 prevalence and mortality in patients with cancer and the effect of primary tumour subtype and patient demographics: a prospective cohort study.

J Clin Oncol 38:2552-2557 (2020). Mehanna H, D Rischin, SJ Wong, V Gregoire, R Ferris, J Waldron, . . . S Porceddu. De-Escalation After DE-ESCALATE and RTOG 1016: A Head and Neck Cancer InterGroup Framework for Future De-Escalation Studies. Find out more online.

Nature 583:807-812 (2020). Middleton G, P Fletcher, S Popat, J Savage, Y Summers, A Greystoke, . . . L Billingham. The National Lung Matrix Trial of personalized therapy in lung cancer. Find out more: Flagship Cancer Research UK precision medicine trial highlights the need for a new approach in treating genomically complicated cancers

Cell Rep 31:107691 (2020). Nafria M, P Keane, ES Ng, EG Stanley, AG Elefanty and C Bonifer. Expression of RUNX1-ETO Rapidly Alters the Chromatin Landscape and Growth of Early Human Myeloid Precursor Cells

Nat Genet 51:151-162 (2019). Assi SA, MR Imperato, DJL Coleman, A Pickin, S Potluri, A Ptasinska, . . . C Bonifer. Subtype-specific regulatory network rewiring in acute myeloid leukemia. Find out more: Research brings personalised medicine to treat leukaemia one step closer

Nat Commun 10:3577 (2019). Bonkhofer F, R Rispoli, P Pinheiro, M Krecsmarik, J Schneider-Swales, IHC Tsang, . . . R Monteiro, T Peterkin, R Patient. Blood stem cell-forming haemogenic endothelium in zebrafish derives from arterial endothelium.

Nature 571:521-527 (2019). Daza-Martin M, K Starowicz, M Jamshad, S Tye, GE Ronson, HL MacKay, . . . JR Morris. Isomerization of BRCA1-BARD1 promotes replication fork protection.

Genes Dev 33:333-347 (2019). Garvin AJ, AK Walker, RM Densham, AS Chauhan, HR Stone, HL Mackay, . . . JR Morris. The deSUMOylase SENP2 coordinates homologous recombination and nonhomologous end joining by independent mechanisms.

PLoS Comput Biol 15:e1006596 (2019). Gendoo DMA, RE Denroche, A Zhang, N Radulovich, GH Jang, M Lemire, . . . B Haibe-Kains. Whole genomes define concordance of matched primary, xenograft, and organoid models of pancreas cancer.

Nat Commun 10:691 (2019). Hadzhiev Y, HK Qureshi, L Wheatley, L Cooper, A Jasiulewicz, H Van Nguyen, . . . F Muller. A cell cycle-coordinated Polymerase II transcription compartment encompasses gene expression before global genome activation.

Cell Rep 28:3022-3031 e3027 (2019). Ptasinska A, A Pickin, SA Assi, PS Chin, L Ames, R Avellino, . . . C Bonifer. RUNX1-ETO Depletion in t(8;21) AML Leads to C/EBPalpha- and AP-1-Mediated Alterations in Enhancer-Promoter Interaction.

Ann Oncol 30:456-463 (2019). Spiteri I, G Caravagna, GD Cresswell, A Vatsiou, D Nichol, A Acar, . . . C Watts, A Sottoriva. Evolutionary dynamics of residual disease in human glioblastoma.

N Engl J Med 381:637-646 (2019). Tamborlane WV, M Barrientos-Perez, U Fainberg, H Frimer-Larsen, M Hafez, PM Hale, . . . T Barrett. Ellipse Trial. Liraglutide in Children and Adolescents with Type 2 Diabetes. 

Cell Rep 25:2061-2069 e2064 (2018). Bowry A, AL Piberger, P Rojas, M Saponaro and E Petermann. BET Inhibition Induces HEXIM1- and RAD51-Dependent Conflicts between Transcription and Replication.

Cancer Cell 34:674-689 e678 (2018). de Boer B, J Prick, MG Pruis, P Keane, MR Imperato, J Jaques, . . .C Bonifer, JJ Schuringa. Prospective Isolation and Characterization of Genetically and Functionally Distinct AML Subclones.

Nat Commun 9:2704 (2018). Gauvrit S, A Villasenor, B Strilic, P Kitchen, MM Collins, R Marin-Juez, . . . PS Jayaraman, DYR Stainier. HHEX is a transcriptional regulator of the VEGFC/FLT4/PROX1 signaling axis during vascular development.

Mol Cell 71:25-41 e26 (2018). Higgs MR, K Sato, JJ Reynolds, S Begum, R Bayley, A Goula, . . . GS Stewart. Histone Methylation by SETD1A Protects Nascent DNA through the Nucleosome Chaperone Activity of FANCD2.

Cancer Cell 34:626-642 e628 (2018). Martinez-Soria N, L McKenzie, J Draper, A Ptasinska, H Issa, S Potluri, . . . C Bonifer, O Heidenreich. The Oncogenic Transcription Factor RUNX1/ETO Corrupts Cell Cycle Regulation to Drive Leukemic Transformation.

PLoS Comput Biol 14:e1006258 (2018). Moradigaravand D, M Palm, A Farewell, V Mustonen, J Warringer and L Parts. Prediction of antibiotic resistance in Escherichia coli from large-scale pan-genome data.

Nat Commun 9:746 (2018). Ronson GE, AL Piberger, MR Higgs, AL Olsen, GS Stewart, PJ McHugh, . . . ND Lakin. PARP1 and PARP2 stabilise replication forks at base excision repair intermediates through Fbh1-dependent Rad51 regulation.

Nat Commun 9:229 (2018). Uckelmann M, RM Densham, R Baas, HHK Winterwerp, A Fish, TK Sixma and JR Morris. USP48 restrains resection by site-specific cleavage of the BRCA1 ubiquitin mark from H2A.

Cell Rep 24:1496-1511 e1498 (2018). Ward C, G Volpe, P Cauchy, A Ptasinska, R Almaghrabi, D Blakemore, . . . P Garcia. Fine-Tuning Mybl2 Is Required for Proper Mesenchymal-to-Epithelial Transition during Somatic Reprogramming.

Nature 559:285-289 (2018). Zimmermann M, O Murina, MAM Reijns, A Agathanggelou, R Challis, Z Tarnauskaite, . . . T Stankovic, AP Jackson, D Durocher. CRISPR screens identify genomic ribonucleotides as a source of PARP-trapping lesions

Cell Rep 21:3498-3513 (2017). Chiang K, AE Zielinska, AM Shaaban, MP Sanchez-Bailon, J Jarrold, TL Clarke, . . . CC Davies. PRMT5 Is a Critical Regulator of Breast Cancer Stem Cell Function via Histone Methylation and FOXP1 Expression.

Mol Cell 65:900-916 e907 (2017). Clarke TL, MP Sanchez-Bailon, K Chiang, JJ Reynolds, J Herrero-Ruiz, TM Bandeiras, . . . CC Davies. PRMT5-Dependent Methylation of the TIP60 Coactivator RUVBL1 Is a Key Regulator of Homologous Recombination.

Cell Rep 19:1654-1668 (2017). Loke J, SA Assi, MR Imperato, A Ptasinska, P Cauchy, Y Grabovska, . . . C Bonifer. RUNX1-ETO and RUNX1-EVI1 Differentially Reprogram the Chromatin Landscape in t(8;21) and t(3;21) AML.

Nat Genet 49:537-549 (2017). Reynolds JJ, LS Bicknell, P Carroll, MR Higgs, R Shaheen, JE Murray, . . . GS Stewart. Mutations in DONSON disrupt replication fork stability and cause microcephalic dwarfism.

Nat Cell Biol 19:468-479 (2017). Sonneville R, SP Moreno, A Knebel, C Johnson, CJ Hastie, A Gartner, . . . A Gambus, K Labib. CUL-2LRR-1 and UBXN-3 drive replisome disassembly during DNA replication termination and mitosis.

Cell 168:843-855 e813 (2017). Williamson L, M Saponaro, S Boeing, P East, R Mitter, T Kantidakis, . . . JQ Svejstrup. UV Irradiation Induces a Non-coding RNA that Functionally Opposes the Protein Encoded by the Same Gene

Cancer Cell 30:578-594 (2016). Bardella C, O Al-Dalahmah, D Krell, P Brazauskas, K Al-Qahtani, M Tomkova, . . . I Tomlinson. Expression of Idh1(R132H) in the Murine Subventricular Zone Stem Cell Niche Recapitulates Features of Early Gliomagenesis.

EMBO J 35:515-535 (2016). Bevington SL, P Cauchy, J Piper, E Bertrand, N Lalli, RC Jarvis, . . . PN Cockerill. Inducible chromatin priming is associated with the establishment of immunological memory in T cells.

PLoS Genet 12:e1005945 (2016). Byrd PJ, GS Stewart, A Smith, C Eaton, AJ Taylor, C Guy, . . . AM Taylor. A Hypomorphic PALB2 Allele Gives Rise to an Unusual Form of FA-N Associated with Lymphoid Tumour Development.

Nat Struct Mol Biol 23:647-655 (2016). Densham RM, AJ Garvin, HR Stone, J Strachan, RA Baldock, M Daza-Martin, . . . JR Morris. Human BRCA1-BARD1 ubiquitin ligase activity counteracts chromatin barriers to DNA resection.

Dev Cell 36:572-587 (2016). Goode DK, N Obier, MS Vijayabaskar, ALM Lie, AJ Lilly, R Hannah, . . . C Bonifer. Dynamic Gene Regulatory Networks Drive Hematopoietic Specification and Differentiation.

Nat Genet 48:36-43 (2016). Harley ME, O Murina, A Leitch, MR Higgs, LS Bicknell, G Yigit, . . . GS Stewart, AP Jackson. TRAIP promotes DNA damage response during genome replication and is mutated in primordial dwarfism.

Genes Dev 30:408-420 (2016). Kantidakis T, M Saponaro, R Mitter, S Horswell, A Kranz, S Boeing, . . . JQ Svejstrup. Mutation of cancer driver MLL2 results in transcription stress and genome instability.

Nat Commun 7:13087 (2016). Kotsantis P, LM Silva, S Irmscher, RM Jones, L Folkes, N Gromak and E Petermann. Increased global transcription activity as a mechanism of replication stress in cancer.

N Engl J Med 374:1444-1454 (2016). Mehanna H, WL Wong, CC McConkey, JK Rahman, M Robinson, AG Hartley, . . . P-NTM Group. PET-CT Surveillance versus Neck Dissection in Advanced Head and Neck Cancer.

Dev Cell 38:358-370 (2016). Monteiro R, P Pinheiro, N Joseph, T Peterkin, J Koth, E Repapi, . . . R Patient. Transforming Growth Factor beta Drives Hemogenic Endothelium Programming and the Transition to Hematopoietic Stem Cells

Cell Rep 12:821-836 (2015). Cauchy P, SR James, J Zacarias-Cabeza, A Ptasinska, MR Imperato, SA Assi, . . . PN Cockerill. Chronic FLT3-ITD Signaling in Acute Myeloid Leukemia Is Connected to a Specific Chromatin Signature.

Mol Cell 59:462-477 (2015). Higgs MR, JJ Reynolds, A Winczura, AN Blackford, V Borel, ES Miller, . . . GS Stewart. BOD1L Is Required to Suppress Deleterious Resection of Stressed Replication Forks.

Lancet 386:249-257 (2015). Kehoe S, J Hook, M Nankivell, GC Jayson, H Kitchener, T Lopes, . . . AM Swart. Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-inferiority trial.

Nat Commun 6:7203 (2015). Regha K, SA Assi, O Tsoulaki, J Gilmour, G Lacaud and C Bonifer. Developmental-stage-dependent transcriptional response to leukaemic oncogene expression

Nat Commun 5:3756 (2014). Cazier JB, SR Rao, CM McLean, AK Walker, BJ Wright, EE Jaeger, . . . FC Hamdy. Whole-genome sequencing of bladder cancers reveals somatic CDKN1A mutations and clinicopathological associations with mutation burden.

Mol Cell 53:645-654 (2014). Feng T, A Yamamoto, SE Wilkins, E Sokolova, LA Yates, M Munzel, . . . ML Coleman. Optimal translational termination requires C4 lysyl hydroxylation of eRF1.

Nature 507:381-385 (2014). Haberle V, N Li, Y Hadzhiev, C Plessy, C Previti, C Nepal, . . . F Muller, B Lenhard. Two independent transcription initiation codes overlap on vertebrate core promoters.

Science 346:477-481 (2014). Moreno SP, R Bailey, N Campion, S Herron and A Gambus. Polyubiquitylation drives replisome disassembly at the termination of DNA replication.

Cell reports 8:1974-1988 (2014). Ptasinska A, SA Assi, N Martinez-Soria, MR Imperato, J Piper, P Cauchy, . . . C Bonifer. Identification of a Dynamic Core Transcriptional Network in t(8;21) AML that Regulates Differentiation Block and Self-Renewal.

Cell 157:1037-1049 (2014). Saponaro M, T Kantidakis, R Mitter, GP Kelly, M Heron, H Williams, . . . JQ Svejstrup. RECQL5 controls transcript elongation and suppresses genome instability associated with transcription stress

EMBO J 32:1556-1567 (2013). Davies CC, A Chakraborty, ME Diefenbacher, M Skehel and A Behrens. Arginine methylation of the c-Jun coactivator RACO-1 is required for c-Jun/AP-1 activation.

EMBO Rep 14:975-983 (2013). Garvin AJ, RM Densham, SA Blair-Reid, KM Pratt, HR Stone, D Weekes, . . . JR Morris. The deSUMOylase SENP7 promotes chromatin relaxation for homologous recombination DNA repair.

Genome Res 23:1938-1950 (2013). Nepal C, Y Hadzhiev, C Previti, V Haberle, N Li, H Takahashi, . . . F Muller. Dynamic regulation of the transcription initiation landscape at single nucleotide resolution during vertebrate embryogenesis.

Nat Genet 45:136-144 (2013). Palles C, JB Cazier, KM Howarth, E Domingo, AM Jones, P Broderick, . . . I Tomlinson. Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas.

Cell Rep 5:1302-1315 (2013). Sarkar S, B Carroll, Y Buganim, D Maetzel, AH Ng, JP Cassady, . . . R Jaenisch. Impaired autophagy in the lipid-storage disorder Niemann-Pick type C1 disease

J Clin Oncol 30:4477-4484 (2012). Bartlett JM, KJ Bloom, T Piper, TJ Lawton, CJ van de Velde, DT Ross, . . . D Rea. Mammostrat as an immunohistochemical multigene assay for prediction of early relapse risk in the tamoxifen versus exemestane adjuvant multicenter trial pathology study.

EMBO J 31:3918-3934 (2012). Butler LR, RM Densham, J Jia, AJ Garvin, HR Stone, V Shah, . . . JR Morris. The proteasomal de-ubiquitinating enzyme POH1 promotes the double-strand DNA break response.

Lancet Oncol 13:1152-1160 (2012). D Morton and Foxtrot Collaborative G. Feasibility of preoperative chemotherapy for locally advanced, operable colon cancer: the pilot phase of a randomised controlled trial.

Nat Chem Biol 8:960-962 (2012). Ge W, A Wolf, T Feng, CH Ho, R Sekirnik, A Zayer, . . . ML Coleman, CJ Schofield. Oxygenase-catalyzed ribosome hydroxylation occurs in prokaryotes and humans.

EMBO J 31:4318-4333 (2012). Lichtinger M, R Ingram, R Hannah, D Muller, D Clarke, SA Assi, . . . C Bonifer. RUNX1 reshapes the epigenetic landscape at the onset of haematopoiesis.

Mol Cell 45:505-516 (2012). Polo SE, AN Blackford, JR Chapman, L Baskcomb, S Gravel, A Rusch, . . . GS Stewart, RJ Grand, SP Jackson. Regulation of DNA-end resection by hnRNPU-like proteins promotes DNA double-strand break signaling and repair.

Cell Rep 2:270-282 (2012). Radulescu S, MJ Brookes, P Salgueiro, RA Ridgway, E McGhee, K Anderson, . . . C Tselepis, OJ Sansom. Luminal iron levels govern intestinal tumorigenesis after Apc loss in vivo.

J Clin Oncol 30:4524-4532 (2012). Skowronska A, A Parker, G Ahmed, C Oldreive, Z Davis, S Richards, . . . T Stankovic. Biallelic ATM inactivation significantly reduces survival in patients treated on the United Kingdom Leukemia Research Fund Chronic Lymphocytic Leukemia 4 trial.