Julian Downward: Publications

  • Mancini, M; Gal, H; Gaborit, N; Mazzeo, L; Romaniello, D; Salame, TM; Lindzen, M; Mahlknecht, G; Enuka, Y; Burton, DGA; Roth, L; Noronha, A; Marrocco, I; Adreka, D; Altstadter, RE; Bousquet, E; Downward, J; Maraver, A; Krizhanovsky, V and Yarden, Y (2018)
    An oligoclonal antibody durably overcomes resistance of lung cancer to third-generation EGFR inhibitors.
    EMBO Molecular Medicine 10, 294-308 PubMed abstract
  • Miess, H; Dankworth, B; Gouw, AM; Rosenfeldt, M; Schmitz, W; Jiang, M; Saunders, B; Howell, M; Downward, J; Felsher, DW; Peck, B and Schulze, A (2018)
    The glutathione redox system is essential to prevent ferroptosis caused by impaired lipid metabolism in clear cell renal cell carcinoma.
    Oncogene [Epub ahead of print] PubMed abstract
  • Soutar, MPM; Kempthorne, L; Miyakawa, S; Annuario, E; Melandri, D; Harley, J; O'Sullivan, GA; Wray, S; Hancock, DC; Cookson, MR; Downward, J; Carlton, M and Plun-Favreau, H (2018)
    AKT signalling selectively regulates PINK1 mitophagy in SHSY5Y cells and human iPSC-derived neurons.
    Scientific Reports 8, 8855 PubMed abstract
  • Coelho, MA; de Carné Trécesson, S; Rana, S; Zecchin, D; Moore, C; Molina-Arcas, M; East, P; Spencer-Dene, B; Nye, E; Barnouin, K; Snijders, AP; Lai, WS; Blackshear, PJ and Downward, J (2017)
    Oncogenic RAS signaling promotes tumor immunoresistance by stabilizing PD-L1 mRNA.
    Immunity 47, 1083-1099 e1086 PubMed abstract
  • Castellano, E; Molina-Arcas, M; Krygowska, AA; East, P; Warne, P; Nicol, A and Downward, J (2016)
    RAS signalling through PI3-Kinase controls cell migration via modulation of Reelin expression.
    Nature Communications 7, 11245 PubMed abstract
  • Houslay, DM; Anderson, KE; Chessa, T; Kulkarni, S; Fritsch, R; Downward, J; Backer, JM; Stephens, LR and Hawkins, PT (2016)
    Coincident signals from GPCRs and receptor tyrosine kinases are uniquely transduced by PI3Kβ in myeloid cells.
    Science Signaling 9, ra82 PubMed abstract
  • Li, H; Stokes, W; Chater, E; Roy, R; de Bruin, E; Hu, Y; Liu, Z; Smit, EF; Heynen, GJJE; Downward, J; Seckl, MJ; Wang, Y; Tang, H and Pardo, OE (2016)
    Decreased glutathione biosynthesis contributes to EGFR T790M-driven erlotinib resistance in non-small cell lung cancer.
    Cell Discovery 2, 16031 PubMed abstract
  • Mathew, G; Hannan, A; Hertzler-Schaefer, K; Wang, F; Feng, G-S; Zhong, J; Zhao, JJ; Downward, J and Zhang, X (2016)
    Targeting of Ras-mediated FGF signaling suppresses Pten-deficient skin tumor.
    Proceedings of the National Academy of Sciences of the United States of America 113, 13156-13161 PubMed abstract
  • Raz, R; Burlina, F; Ismail, M; Downward, J; Li, J; Smerdon, SJ; Quibell, M; White, PD and Offer, J (2016)
    HF-free Boc synthesis of peptide thioesters for ligation and cyclization.
    Angewandte Chemie International Edition 55, 13174-13179 PubMed abstract
  • Downward, J (2015)
    RAS synthetic lethal screens revisited: Still seeking the elusive prize?
    Clinical Cancer Research 21, 1802-1809 PubMed abstract
  • Fritsch, R; Fritsch, K; Sommer, S; DeKrijger, I and Downward, J (2015)
    RAC1 selectively engages the β isoform of PI3K in PTEN loss.
    Oncology Research and Treatment 38, 249, Abstract P814
  • Gatto, F; Miess, H; Schulze, A and Nielsen, J (2015)
    Flux balance analysis predicts essential genes in clear cell renal cell carcinoma metabolism.
    Scientific Reports 5, 10738 PubMed abstract
  • Godin-Heymann, N; Brabetz, S; Murillo, MM; Saponaro, M; Santos, CR; Lobley, A; East, P; Chakravarty, P; Matthews, N; Kelly, G; Jordan, S; Castellano, E and Downward, J (2015)
    Tumour-suppression function of KLF12 through regulation of anoikis.
    Oncogene 35, 3324-3334 PubMed abstract
  • Mancini, M; Gaborit, N; Lindzen, M; Meir Salame, T; Dall'Ora, M; Sevilla-Sharon, M; Abdul-Hai, A; Downward, J and Yarden, Y (2015)
    Combining three antibodies nullifies feedback-mediated resistance to erlotinib in lung cancer.
    Science Signaling 8, ra53 PubMed abstract
  • Pender, A; Garcia-Murillas, I; Rana, S; Cutts, RJ; Kelly, G; Fenwick, K; Kozarewa, I; Gonzalez de Castro, D; Bhosle, J; O'Brien, M; Turner, NC; Popat, S and Downward, J (2015)
    Efficient genotyping of KRAS mutant non-small cell lung cancer using a multiplexed droplet digital PCR approach.
    PLOS ONE 10, e0139074 PubMed abstract
  • Sheridan, C (2015)
    Evading inhibitory constraints - destabilizing p110α/p85α interactions.
    FEBS Journal 282, 3525-3527 PubMed abstract
  • Sheridan, C and Downward, J (2015)
    Overview of KRAS-driven genetically engineered mouse models of non-small cell lung cancer.
    In: Current Protocols in Pharmacology. 2015 edition.
    Wiley, 2015. Unit 14.35.
  • Smith, D; Armenteros, E; Percy, L; Kumar, M; Lach, A; Herledan, G; Stubbs, M; Downward, J and Yong, K (2015)
    RAS mutation status and bortezomib therapy for relapsed multiple myeloma.
    British Journal of Haematology 169, 905-908 PubMed abstract
  • de Bruin, EC; Cowell, C; Warne, PH; Jiang, M; Saunders, RE; Melnick, MA; Gettinger, S; Walther, Z; Wurtz, A; Heynen, GJ; Heideman, DAM; Gómez-Román, J; García-Castaño, A; Gong, Y; Ladanyi, M; Varmus, H; Bernards, R; Smit, EF; Politi, K and Downward, J (2014)
    Reduced NF1 expression confers resistance to EGFR inhibition in lung cancer.
    Cancer Discovery 4, 606-619 PubMed abstract
  • Downward, J (2014)
    RAS's cloak of invincibility slips at last?
    Cancer Cell 25, 5-6 PubMed abstract
  • Endesfelder, D; Burrell, RA; Kanu, N; McGranahan, N; Howell, M; Parker, PJ; Downward, J; Swanton, C and Kschischo, M (2014)
    Chromosomal instability selects gene copy-number variants encoding core regulators of proliferation in ER+ breast cancer.
    Cancer Research 74, 4853-4863 PubMed abstract
  • Geraghty, RJ; Capes-Davis, A; Davis, JM; Downward, J; Freshney, RI; Knezevic, I; Lovell-Badge, R; Masters, JRW; Meredith, J; Stacey, GN; Thraves, P and Vias, M (2014)
    Guidelines for the use of cell lines in biomedical research.
    British Journal of Cancer 111, 1021-1046 PubMed abstract
  • Linch, M; Sanz-Garcia, M; Rosse, C; Riou, P; Peel, N; Madsen, CD; Sahai, E; Downward, J; Khwaja, A; Dillon, C; Roffey, J; Cameron, AJM and Parker, PJ (2014)
    Regulation of polarized morphogenesis by protein kinase C iota in oncogenic epithelial spheroids.
    Carcinogenesis 35, 396-406 PubMed abstract
  • Murillo, MM; Zelenay, S; Nye, E; Castellano, E; Lassailly, F; Stamp, G and Downward, J (2014)
    RAS interaction with PI3K p110α is required for tumor-induced angiogenesis.
    Journal of Clinical Investigation 124, 3601-3611 PubMed abstract
  • Wang, Y; Bu, F; Royer, C; Serres, S; Larkin, JR; Soto, MS; Sibson, NR; Salter, V; Fritzsche, F; Turnquist, C; Koch, S; Zak, J; Zhong, S; Wu, G; Liang, A; Olofsen, PA; Moch, H; Hancock, DC; Downward, J; Goldin, RD; Zhao, J; Tong, X; Guo, Y and Lu, X (2014)
    ASPP2 controls epithelial plasticity and inhibits metastasis through β-catenin-dependent regulation of ZEB1.
    Nature Cell Biology 16, 1092-1104 PubMed abstract
  • Castellano, E; Sheridan, C; Thin, MZ; Nye, E; Spencer-Dene, B; Diefenbacher, ME; Moore, C; Kumar, MS; Murillo, MM; Grönroos, E; Lassailly, F; Stamp, G and Downward, J (2013)
    Requirement for interaction of PI3-kinase p110α with RAS in lung tumor maintenance.
    Cancer Cell 24, 617-630 PubMed abstract
  • Fritsch, R; de Krijger, I; Fritsch, K; George, R; Reason, B; Kumar, MS; Diefenbacher, M; Stamp, G and Downward, J (2013)
    RAS and RHO families of GTPases directly regulate distinct phosphoinositide 3-kinase isoforms.
    Cell 153, 1050-1063 PubMed abstract
  • Fritsch, R and Downward, J (2013)
    SnapShot: Class I PI3K isoform signaling.
    Cell 154, 940-940 e941 PubMed abstract
  • Molina-Arcas, M; Hancock, DC; Sheridan, C; Kumar, MS and Downward, J (2013)
    Coordinate direct input of both KRAS and IGF1 receptor to activation of PI3 kinase in KRAS-mutant lung cancer.
    Cancer Discovery 3, 548-563 PubMed abstract
  • Sheridan, C and Downward, J (2013)
    Inhibiting the RAS-PI3K pathway in cancer therapy.
    In: The Enzymes. Edited by Tamanoi, F and Der, CJ.
    Academic Press, 2013. 34 , 107-136.
  • Weigelt, B; Warne, PH; Lambros, MB; Reis-Filho, JS and Downward, J (2013)
    PI3K pathway dependencies in endometrioid endometrial cancer cell lines.
    Clinical Cancer Research 19, 3533-3544 PubMed abstract
  • Bögel, G; Gujdár, A; Geiszt, M; Lányi, Á; Fekete, A; Sipeki, S; Downward, J and Buday, L (2012)
    Frank-ter Haar syndrome protein Tks4 regulates epidermal growth factor-dependent cell migration.
    Journal of Biological Chemistry 287, 31321-31329 PubMed abstract
  • Cully, M and Downward, J (2012)
    Assessing cell size and cell cycle regulation in cells with altered TOR activity.
    Methods in Molecular Biology 821, 227-237 PubMed abstract
  • Gerlinger, M; Rowan, AJ; Horswell, S; Larkin, J; Endesfelder, D; Gronroos, E; Martinez, P; Matthews, N; Stewart, A; Tarpey, P; Varela, I; Phillimore, B; Begum, S; McDonald, NQ; Butler, A; Jones, D; Raine, K; Latimer, C; Santos, CR; Nohadani, M; Eklund, AC; Spencer-Dene, B; Clark, G; Pickering, L; Stamp, G; Gore, M; Szallasi, Z; Downward, J; Futreal, PA and Swanton, C (2012)
    Intratumor heterogeneity and branched evolution revealed by multiregion sequencing.
    New England Journal of Medicine 366, 883-892 PubMed abstract
  • Kumar, MS; Hancock, DC; Molina-Arcas, M; Steckel, M; East, P; Diefenbacher, M; Armenteros-Monterroso, E; Lassailly, F; Matthews, N; Nye, E; Stamp, G; Behrens, A and Downward, J (2012)
    The GATA2 transcriptional network is requisite for RAS oncogene-driven non-small cell lung cancer.
    Cell 149, 642-655 PubMed abstract
  • Lee, AJX; Roylance, R; Sander, J; Gorman, P; Endesfelder, D; Kschischo, M; Jones, NP; East, P; Nicke, B; Spassieva, S; Obeid, LM; Birkbak, NJ; Szallasi, Z; McKnight, NC; Rowan, AJ; Speirs, V; Hanby, AM; Downward, J; Tooze, SA and Swanton, C (2012)
    CERT depletion predicts chemotherapy benefit and mediates cytotoxic and polyploid-specific cancer cell death through autophagy induction.
    Journal of Pathology 226, 482-494 PubMed abstract
  • Molina-Arcas, M and Downward, J (2012)
    How to fool a wonder drug: truncate and dimerize.
    Cancer Cell 21, 7-9 PubMed abstract
  • Steckel, M; Molina-Arcas, M; Weigelt, B; Marani, M; Warne, PH; Kuznetsov, H; Kelly, G; Saunders, B; Howell, M; Downward, J and Hancock, DC (2012)
    Determination of synthetic lethal interactions in KRAS oncogene-dependent cancer cells reveals novel therapeutic targeting strategies.
    Cell Research 22, 1227-1245 PubMed abstract
  • Weigelt, B and Downward, J (2012)
    Genomic determinants of PI3K pathway inhibitor response in cancer.
    Frontiers in Oncology 2, 109 PubMed abstract
  • Castellano, E and Downward, J (2011)
    RAS interaction with PI3K: more than just another effector pathway.
    Genes & Cancer 2, 261-274 PubMed abstract
  • Downward, J (2011)
    Targeting RAF: trials and tribulations.
    Nature Medicine 17, 286-288 PubMed abstract
  • Lara, R; Mauri, FA; Taylor, H; Derua, R; Shia, A; Gray, C; Nicols, A; Shiner, RJ; Schofield, E; Bates, PA; Waelkens, E; Dallman, M; Lamb, J; Zicha, D; Downward, J; Seckl, MJ and Pardo, OE (2011)
    An siRNA screen identifies RSK1 as a key modulator of lung cancer metastasis.
    Oncogene 30, 3513-3521 PubMed abstract
  • Lee, AJX; Endesfelder, D; Rowan, AJ; Walther, A; Birkbak, NJ; Futreal, PA; Downward, J; Szallasi, Z; Tomlinson, IPM; Howell, M; Kschischo, M and Swanton, C (2011)
    Chromosomal instability confers intrinsic multidrug resistance.
    Cancer Research 71, 1858-1870 PubMed abstract
  • Roylance, R; Endesfelder, D; Gorman, P; Burrell, RA; Sander, J; Tomlinson, I; Hanby, AM; Speirs, V; Richardson, AL; Birkbak, NJ; Eklund, AC; Downward, J; Kschischo, M; Szallasi, Z and Swanton, C (2011)
    Relationship of extreme chromosomal instability with long-term survival in a retrospective analysis of primary breast cancer.
    Cancer Epidemiology, Biomarkers & Prevention 20, 2183-2194 PubMed abstract
  • Schulze, A and Downward, J (2011)
    Flicking the Warburg switch-tyrosine phosphorylation of pyruvate dehydrogenase kinase regulates mitochondrial activity in cancer cells.
    Molecular Cell 44, 846-848 PubMed abstract
  • Weigelt, B; Warne, PH and Downward, J (2011)
    PIK3CA mutation, but not PTEN loss of function, determines the sensitivity of breast cancer cells to mTOR inhibitory drugs.
    Oncogene 30, 3222-3233 PubMed abstract
  • Alfano, D; Votta, G; Schulze, A; Downward, J; Caputi, M; Stoppelli, MP and Iaccarino, I (2010)
    Modulation of cellular migration and survival by c-Myc through the downregulation of urokinase (uPA) and uPA receptor.
    Molecular and Cellular Biology 30, 1838-1851 PubMed abstract
  • Castellano, E and Downward, J (2010)
    Role of RAS in the regulation of PI 3-kinase.
    Current Topics in Microbiology and Immunology 346, 143-169 PubMed abstract
  • Cully, M; Genevet, A; Warne, P; Treins, C; Liu, T; Bastien, J; Baum, B; Tapon, N; Leevers, SJ and Downward, J (2010)
    A role for p38 stress-activated protein kinase in regulation of cell growth via TORC1.
    Molecular and Cellular Biology 30, 481-495 PubMed abstract
  • Swanton, C; Larkin, JM; Gerlinger, M; Eklund, AC; Howell, M; Stamp, G; Downward, J; Gore, M; Futreal, PA; Escudier, B; Andre, F; Albiges, L; Beuselinck, B; Oudard, S; Hoffmann, J; Gyorffy, B; Torrance, CJ; Boehme, KA; Volkmer, H; Toschi, L; Nicke, B; Beck, M and Szallasi, Z (2010)
    Predictive biomarker discovery through the parallel integration of clinical trial and functional genomics datasets.
    Genome Medicine 2, 53 PubMed abstract
  • Treins, C and Downward, J (2010)
    mTORC2: the other facet of mTOR.
    In: The Enzymes. Edited by Fuyuhiko, T and Michael, NH.
    Academic Press, 2010. 28, 99-124.
  • Treins, C; Warne, PH; Magnuson, MA; Pende, M and Downward, J (2010)
    Rictor is a novel target of p70 S6 kinase-1.
    Oncogene 29, 1003-1016 PubMed abstract
  • Vento, MT; Zazzu, V; Loffreda, A; Cross, JR; Downward, J; Stoppelli, MP and Iaccarino, I (2010)
    Praf2 is a novel Bcl-xL/Bcl-2 interacting protein with the ability to modulate survival of cancer cells.
    PLOS ONE 5, e15636 PubMed abstract
  • Wang, Y; Ngo, VN; Marani, M; Yang, Y; Wright, G; Staudt, LM and Downward, J (2010)
    Critical role for transcriptional repressor Snail2 in transformation by oncogenic RAS in colorectal carcinoma cells.
    Oncogene 29, 4658-4670 PubMed abstract
  • Zeller, KS; Idevall-Hagren, O; Stefansson, A; Velling, T; Jackson, SP; Downward, J; Tengholm, A and Johansson, S (2010)
    PI3-kinase p110α mediates β1 integrin-induced Akt activation and membrane protrusion during cell attachment and initial spreading.
    Cellular Signalling 22, 1838-1848 PubMed abstract
  • Chua, BT; Gallego-Ortega, D; Ramirez de Molina, A; Ullrich, A; Lacal, JC and Downward, J (2009)
    Regulation of Akt(ser473) phosphorylation by choline kinase in breast carcinoma cells.
    Molecular Cancer 8, 131 PubMed abstract

[Page last updated 1 Jul 2018]

Julian Downward

+44 (0)20 379 61838

  • Qualifications and history
  • 1986 PhD in Natural Sciences, Imperial College, London University, UK
  • 1986 Postdoctoral Research Fellow, Massachusetts Institute of Technology, USA
  • 1989 Established lab at the Imperial Cancer Research Fund (in 2002 the Imperial Cancer Research Fund became Cancer Research UK)
  • 2015 Associate Research Director, the Francis Crick Institute, London, UK