Now showing items 1-7 of 7

    • ATR Is a Therapeutic Target in Synovial Sarcoma. 

      Jones, SE; Fleuren, EDG; Frankum, J; Konde, A; Williamson, CT; Krastev, DB; Pemberton, HN; Campbell, J; Gulati, A; Elliott, R; Menon, M; Selfe, JL; Brough, R; Pettitt, SJ; Niedzwiedz, W; van der Graaf, WTA; Shipley, J; Ashworth, A; Lord, CJ (2017-12-15)
      Synovial sarcoma (SS) is an aggressive soft-tissue malignancy characterized by expression of SS18-SSX fusions, where treatment options are limited. To identify therapeutically actionable genetic dependencies in SS, we ...
    • Coupling bimolecular PARylation biosensors with genetic screens to identify PARylation targets. 

      Krastev, DB; Pettitt, SJ; Campbell, J; Song, F; Tanos, BE; Stoynov, SS; Ashworth, A; Lord, CJ (2018-05-22)
      Poly (ADP-ribose)ylation is a dynamic protein modification that regulates multiple cellular processes. Here, we describe a system for identifying and characterizing PARylation events that exploits the ability of a PBZ ...
    • DNA repair deficiency sensitizes lung cancer cells to NAD+ biosynthesis blockade. 

      Touat, M; Sourisseau, T; Dorvault, N; Chabanon, RM; Garrido, M; Morel, D; Krastev, DB; Bigot, L; Adam, J; Frankum, JR; Durand, S; Pontoizeau, C; Souquère, S; Kuo, M-S; Sauvaigo, S; Mardakheh, F; Sarasin, A; Olaussen, KA; Friboulet, L; Bouillaud, F; Pierron, G; Ashworth, A; Lombès, A; Lord, CJ; Soria, J-C; Postel-Vinay, S (2018-04-02)
      Synthetic lethality is an efficient mechanism-based approach to selectively target DNA repair defects. Excision repair cross-complementation group 1 (ERCC1) deficiency is frequently found in non-small-cell lung cancer ...
    • E-Cadherin/ROS1 Inhibitor Synthetic Lethality in Breast Cancer. 

      Bajrami, I; Marlow, R; van de Ven, M; Brough, R; Pemberton, HN; Frankum, J; Song, F; Rafiq, R; Konde, A; Krastev, DB; Menon, M; Campbell, J; Gulati, A; Kumar, R; Pettitt, SJ; Gurden, MD; Cardenosa, ML; Chong, I; Gazinska, P; Wallberg, F; Sawyer, EJ; Martin, L-A; Dowsett, M; Linardopoulos, S; Natrajan, R; Ryan, CJ; Derksen, PWB; Jonkers, J; Tutt, ANJ; Ashworth, A; Lord, CJ (2018-04)
      The cell adhesion glycoprotein E-cadherin (CDH1) is commonly inactivated in breast tumors. Precision medicine approaches that exploit this characteristic are not available. Using perturbation screens in breast tumor cells ...
    • Genome-wide and high-density CRISPR-Cas9 screens identify point mutations in PARP1 causing PARP inhibitor resistance. 

      Pettitt, SJ; Krastev, DB; Brandsma, I; Dréan, A; Song, F; Aleksandrov, R; Harrell, MI; Menon, M; Brough, R; Campbell, J; Frankum, J; Ranes, M; Pemberton, HN; Rafiq, R; Fenwick, K; Swain, A; Guettler, S; Lee, J-M; Swisher, EM; Stoynov, S; Yusa, K; Ashworth, A; Lord, CJ (2018-05-10)
      Although PARP inhibitors (PARPi) target homologous recombination defective tumours, drug resistance frequently emerges, often via poorly understood mechanisms. Here, using genome-wide and high-density CRISPR-Cas9 ...
    • Genome-wide barcoded transposon screen for cancer drug sensitivity in haploid mouse embryonic stem cells. 

      Pettitt, SJ; Krastev, DB; Pemberton, HN; Fontebasso, Y; Frankum, J; Rehman, FL; Brough, R; Song, F; Bajrami, I; Rafiq, R; Wallberg, F; Kozarewa, I; Fenwick, K; Armisen-Garrido, J; Swain, A; Gulati, A; Campbell, J; Ashworth, A; Lord, CJ (2017-03-01)
      We describe a screen for cellular response to drugs that makes use of haploid embryonic stem cells. We generated ten libraries of mutants with piggyBac gene trap transposon integrations, totalling approximately 100,000 ...
    • The shieldin complex mediates 53BP1-dependent DNA repair. 

      Noordermeer, SM; Adam, S; Setiaputra, D; Barazas, M; Pettitt, SJ; Ling, AK; Olivieri, M; Álvarez-Quilón, A; Moatti, N; Zimmermann, M; Annunziato, S; Krastev, DB; Song, F; Brandsma, I; Frankum, J; Brough, R; Sherker, A; Landry, S; Szilard, RK; Munro, MM; McEwan, A; Goullet de Rugy, T; Lin, Z-Y; Hart, T; Moffat, J; Gingras, A-C; Martin, A; van Attikum, H; Jonkers, J; Lord, CJ; Rottenberg, S; Durocher, D (2018-08)
      53BP1 is a chromatin-binding protein that regulates the repair of DNA double-strand breaks by suppressing the nucleolytic resection of DNA termini1,2. This function of 53BP1 requires interactions with PTIP3 and RIF14-9, ...