Now showing items 1-13 of 13

    • Association with Aurora-A Controls N-MYC-Dependent Promoter Escape and Pause Release of RNA Polymerase II during the Cell Cycle. 

      Büchel, G; Carstensen, A; Mak, K-Y; Roeschert, I; Leen, E; Sumara, O; Hofstetter, J; Herold, S; Kalb, J; Baluapuri, A; Poon, E; Kwok, C; Chesler, L; Maric, HM; Rickman, DS; Wolf, E; Bayliss, R; Walz, S; Eilers, M (2017-12)
      MYC proteins bind globally to active promoters and promote transcriptional elongation by RNA polymerase II (Pol II). To identify effector proteins that mediate this function, we performed mass spectrometry on N-MYC complexes ...
    • Combined MYC and P53 defects emerge at medulloblastoma relapse and define rapidly progressive, therapeutically targetable disease. 

      Hill, RM; Kuijper, S; Lindsey, JC; Petrie, K; Schwalbe, EC; Barker, K; Boult, JKR; Williamson, D; Ahmad, Z; Hallsworth, A; Ryan, SL; Poon, E; Robinson, SP; Ruddle, R; Raynaud, FI; Howell, L; Kwok, C; Joshi, A; Nicholson, SL; Crosier, S; Ellison, DW; Wharton, SB; Robson, K; Michalski, A; Hargrave, D; Jacques, TS; Pizer, B; Bailey, S; Swartling, FJ; Weiss, WA; Chesler, L; Clifford, SC (2015-01)
      We undertook a comprehensive clinical and biological investigation of serial medulloblastoma biopsies obtained at diagnosis and relapse. Combined MYC family amplifications and P53 pathway defects commonly emerged at relapse, ...
    • Cyclin-Dependent Kinase Inhibitor AT7519 as a Potential Drug for MYCN-Dependent Neuroblastoma. 

      Dolman, MEM; Poon, E; Ebus, ME; den Hartog, IJM; van Noesel, CJM; Jamin, Y; Hallsworth, A; Robinson, SP; Petrie, K; Sparidans, RW; Kok, RJ; Versteeg, R; Caron, HN; Chesler, L; Molenaar, JJ (2015-11)
      <h4>Purpose</h4>MYCN-dependent neuroblastomas have low cure rates with current multimodal treatment regimens and novel therapeutic drugs are therefore urgently needed. In previous preclinical studies, we have shown that ...
    • Detection of the prodrug-activating enzyme carboxypeptidase G2 activity with chemical exchange saturation transfer magnetic resonance. 

      Jamin, Y; Eykyn, TR; Poon, E; Springer, CJ; Robinson, SP (2014-04)
      <h4>Purpose</h4>The purpose of this study is to evaluate if the differential exchange rates with bulk water between amine and amide protons can be exploited using chemical exchange saturation transfer magnetic resonance ...
    • Enhancer invasion shapes MYCN-dependent transcriptional amplification in neuroblastoma. 

      Zeid, R; Lawlor, MA; Poon, E; Reyes, JM; Fulciniti, M; Lopez, MA; Scott, TG; Nabet, B; Erb, MA; Winter, GE; Jacobson, Z; Polaski, DR; Karlin, KL; Hirsch, RA; Munshi, NP; Westbrook, TF; Chesler, L; Lin, CY; Bradner, JE (2018-04)
      Amplification of the locus encoding the oncogenic transcription factor MYCN is a defining feature of high-risk neuroblastoma. Here we present the first dynamic chromatin and transcriptional landscape of MYCN perturbation ...
    • Glycogen synthase kinase 3 controls migration of the neural crest lineage in mouse and Xenopus. 

      Gonzalez Malagon, SG; Lopez Muñoz, AM; Doro, D; Bolger, TG; Poon, E; Tucker, ER; Adel Al-Lami, H; Krause, M; Phiel, CJ; Chesler, L; Liu, KJ (2018-03-19)
      Neural crest migration is critical to its physiological function. Mechanisms controlling mammalian neural crest migration are comparatively unknown, due to difficulties accessing this cell population in vivo. Here we report ...
    • <i>In Vivo</i> Modeling of Chemoresistant Neuroblastoma Provides New Insights into Chemorefractory Disease and Metastasis. 

      Yogev, O; Almeida, GS; Barker, KT; George, SL; Kwok, C; Campbell, J; Zarowiecki, M; Kleftogiannis, D; Smith, LM; Hallsworth, A; Berry, P; Möcklinghoff, T; Webber, HT; Danielson, LS; Buttery, B; Calton, EA; da Costa, BM; Poon, E; Jamin, Y; Lise, S; Veal, GJ; Sebire, N; Robinson, SP; Anderson, J; Chesler, L (2019-10)
      Neuroblastoma is a pediatric cancer that is frequently metastatic and resistant to conventional treatment. In part, a lack of natively metastatic, chemoresistant <i>in vivo</i> models has limited our insight into the ...
    • MRI Imaging of the Hemodynamic Vasculature of Neuroblastoma Predicts Response to Antiangiogenic Treatment. 

      Zormpas-Petridis, K; Jerome, NP; Blackledge, MD; Carceller, F; Poon, E; Clarke, M; McErlean, CM; Barone, G; Koers, A; Vaidya, SJ; Marshall, LV; Pearson, ADJ; Moreno, L; Anderson, J; Sebire, N; McHugh, K; Koh, D-M; Yuan, Y; Chesler, L; Robinson, SP; Jamin, Y (2019-06)
      Childhood neuroblastoma is a hypervascular tumor of neural origin, for which antiangiogenic drugs are currently being evaluated; however, predictive biomarkers of treatment response, crucial for successful delivery of ...
    • Noninvasive detection of carboxypeptidase G2 activity in vivo. 

      Jamin, Y; Smyth, L; Robinson, SP; Poon, ESC; Eykyn, TR; Springer, CJ; Leach, MO; Payne, GS (2011-05)
      The pseudomonad protein, carboxypeptidase G2 (CPG2), is a prodrug-activating enzyme utilized in the targeted chemotherapy strategies of antibody- and gene-directed enzyme prodrug therapy (ADEPT and GDEPT). We have developed ...
    • Noninvasive MRI Native T<sub>1</sub> Mapping Detects Response to <i>MYCN</i>-targeted Therapies in the Th-<i>MYCN</i> Model of Neuroblastoma. 

      Zormpas-Petridis, K; Poon, E; Clarke, M; Jerome, NP; Boult, JKR; Blackledge, MD; Carceller, F; Koers, A; Barone, G; Pearson, ADJ; Moreno, L; Anderson, J; Sebire, N; McHugh, K; Koh, D-M; Chesler, L; Yuan, Y; Robinson, SP; Jamin, Y (2020-08)
      Noninvasive early indicators of treatment response are crucial to the successful delivery of precision medicine in children with cancer. Neuroblastoma is a common solid tumor of young children that arises from anomalies ...
    • Orally bioavailable CDK9/2 inhibitor shows mechanism-based therapeutic potential in MYCN-driven neuroblastoma. 

      Poon, E; Liang, T; Jamin, Y; Walz, S; Kwok, C; Hakkert, A; Barker, K; Urban, Z; Thway, K; Zeid, R; Hallsworth, A; Box, G; Ebus, ME; Licciardello, MP; Sbirkov, Y; Lazaro, G; Calton, E; Costa, BM; Valenti, M; De Haven Brandon, A; Webber, H; Tardif, N; Almeida, GS; Christova, R; Boysen, G; Richards, MW; Barone, G; Ford, A; Bayliss, R; Clarke, PA; De Bono, J; Gray, NS; Blagg, J; Robinson, SP; Eccles, SA; Zheleva, D; Bradner, JE; Molenaar, J; Vivanco, I; Eilers, M; Workman, P; Lin, CY; Chesler, L (2020-11)
      The undruggable nature of oncogenic Myc transcription factors poses a therapeutic challenge in neuroblastoma, a pediatric cancer in which MYCN amplification is strongly associated with unfavorable outcome. Here, we show ...
    • p53 Loss in MYC-Driven Neuroblastoma Leads to Metabolic Adaptations Supporting Radioresistance. 

      Yogev, O; Barker, K; Sikka, A; Almeida, GS; Hallsworth, A; Smith, LM; Jamin, Y; Ruddle, R; Koers, A; Webber, HT; Raynaud, FI; Popov, S; Jones, C; Petrie, K; Robinson, SP; Keun, HC; Chesler, L (2016-05)
      Neuroblastoma is the most common childhood extracranial solid tumor. In high-risk cases, many of which are characterized by amplification of MYCN, outcome remains poor. Mutations in the p53 (TP53) tumor suppressor are rare ...
    • Structural basis of N-Myc binding by Aurora-A and its destabilization by kinase inhibitors. 

      Richards, MW; Burgess, SG; Poon, E; Carstensen, A; Eilers, M; Chesler, L; Bayliss, R (2016-11-11)
      Myc family proteins promote cancer by inducing widespread changes in gene expression. Their rapid turnover by the ubiquitin-proteasome pathway is regulated through phosphorylation of Myc Box I and ubiquitination by the E3 ...