Selected research publications

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

Developmental Cell 57:2584-2598 e2511 (2022). Kataura T, L Sedlackova, EG Otten, R Kumari, D Shapira, F Scialo, . . .S Sarkar and VI Korolchuk. Autophagy promotes cell survival by maintaining NAD levels.

Sci Adv 8:eabq2611 (2022). Taylor MJ, AM Thompson, S Alhajlah, RI Tuxworth and Z Ahmed. Inhibition of Chk2 promotes neuroprotection, axon regeneration, and functional recovery after CNS injury.

Clin Transl Med 12:e962 (2022). Ahmed Z and RI Tuxworth. The brain-penetrant ATM inhibitor, AZD1390, promotes axon regeneration and functional recovery in preclinical models of spinal cord injury.

Blood doi: 10.1182/blood.2021015036  (2022). Tirtakusuma R, K Szoltysek, P Milne, V Grinev, A Ptasinska, PS Chin, . . . C Bonifer, O Heidenreich, S Bomken. Epigenetic regulator genes direct lineage switching in MLL/AF4 leukaemia.

Elife 11 (2022). Vilaplana-Lopera N, V Cuminetti, R Almaghrabi, G Papatzikas, AK Rout, M Jeeves, . . . P Garcia. Crosstalk between AML and stromal cells triggers acetate secretion through the metabolic rewiring of stromal cells.

Nat Genet 54:1037-1050 (2022). Baranasic D, M Hortenhuber, PJ Balwierz, T Zehnder, AK Mukarram, C Nepal, . . . F Muller. Multiomic atlas with functional stratification and developmental dynamics of zebrafish cis-regulatory elements.

J Clin Invest 132 (2022). Abu-Libdeh B, SS Jhujh, S Dhar, JA Sommers, A Datta, GM Longo, . . . GS Stewart. RECON syndrome is a genome instability disorder caused by mutations in the DNA helicase RECQL1.wart

Mol Cell 82:1924-1939 e1910 (2022). Bayley R, V Borel, RJ Moss, E Sweatman, P Ruis, A Ormrod, . . . MR Higgs. H3K4 methylation by SETD1A/BOD1L facilitates RIF1-dependent NHEJ.

Lancet 398:1427-1435 (2021). Karwath A, KV Bunting, SK Gill, O Tica, S Pendleton, F Aziz, . . . GV Ghoutos, D Kotecha, The cadrdAlc group and the Beta-blockers in Heart Failure Collaborative. Redefining beta-blocker response in heart failure patients with sinus rhythm and atrial fibrillation: a machine learning cluster analysis.

Front Immunol 12:642807 (2021). Bevington SL, R Fiancette, DW Gajdasik, P Keane, JK Soley, CM Willis, . . . PN Cockerill. Stable Epigenetic Programming of Effector and Central Memory CD4 T Cells Occurs Within 7 Days of Antigen Exposure In Vivo.

EMBO Rep 22:e51120 (2021). Blakemore D, N Vilaplana-Lopera, R Almaghrabi, E Gonzalez, M Moya, C Ward, . . . P Garcia. MYBL2 and ATM suppress replication stress in pluripotent stem cells.

Nat Comm 12: 6313 (2021). M-P Sanchez-Bailon M-P, S-Y Choi, ER Dufficy, K Sharma, GS McNee, … CC Davies. Arginine methylation and ubiquitylation crosstalk controls DNA end-resection and homologous recombination repair.

PNAS (Proceedings of the National Academy of Sciences of the United States of America) 118 (39) (2021 Regina Andrijes, Rahul K. Hejmadi, Matthew Pugh, Sundaresan Rajesh, Vera Novitskaya, Maha Ibrahim, Michael Overduin, Chris Tselepis, Gary W. Middleton, Balázs Győrffy,  Andrew D. Beggs, and Fedor Berditchevski Tetraspanin 6 is a regulator of carcinogenesis in colorectal cancer.

Lancet 397:387-397 (2021). Bhangu A and Global Surgery Collaborative and National Institute for Health Research Global Health Research Unit on Global Surgery. Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries.

Cell Reports 35:109010 (2021). Potluri S, SA Assi, PS Chin, DJL Coleman, A Pickin, S Moriya, . . . PN Cockerill, C Bonifer. Isoform-specific and signaling-dependent propagation of acute myeloid leukemia by Wilms tumor 1.

Cell Reports 34:108759 (2021). Wang J, P Rojas, J Mao, M Muste Sadurni, O Garnier, S Xiao, . . . MR Higgs, P Garcia,  M Saponaro. Persistence of RNA transcription during DNA replication delays duplication of transcription start sites until G2/M.

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.