Staff Profile

Daniel Williamson completed a BSc(Hons) Genetics at Nottingham University followed by a PhD and  Post-Doc studying the genetics of Rhabdomyosarcoma at The Institute of Cancer Research. He won a Marie-Curie fellowship from the European Commission to move to Institut Curie in Paris investigating childhood cancer genetics and gaining expertise in Bioinformatics and genomics analysis. He was appointed Lecturer in Paediatric Neuro-Oncology at the Northern Institute for Cancer Research at Newcastle University in 2010.

Malignant Rhabdoid Tumours (MRT) are highly aggressive brain tumours which occur primarily in infants and have an extremely poor prognosis (15-30% survival). Rhabdoid tumours may occur in any part of the body and share a common pathology and biology (ATRT is the term for rhabdoid tumours of the CNS).

The genetic cause of rhabdoid tumours is well-established and unusually singular; biallelic inactivation of SMARCB1,  a subunit of the SWI/SNF chromatin remodelling complex, is sufficient to cause >90% of ATRT.

Re-expressing a functional copy of SMARCB1  in MRT cells induces growth arrest and differentiation, effectively causing MRT cells to revert to normal. There are no other recurrent mutations or copy number changes; in some instances SMARCB1  loss is the sole mutational change . The primacy of SMARCB1  mutation offers a clear route to targeted therapies, however we lack the mechanistic knowledge to rationally select effective biological targets for therapeutic intervention. Since 2012, we have led a unique CCLG Biological study, which implements a co-ordinated approach to ATRT translational research, allowing us to collect and profile retrospective and prospective cohorts from the U.K.

• Schwalbe EC, Hicks D, Rafiee G, Bashton M, Gohlke H, Enshaei A, Potluri S, Matthiesen J, Mather M, Taleongpong P, Chaston R, Silmon A, Curtis A, Lindsey JC, Crosier S, Smith AJ, Goschzik T, Doz F, Rutkowski S, Lannering B, Pietsch T, Bailey S, Williamson D, Clifford SC. Minimal methylation classifier (MIMIC): A novel method for derivation and rapid diagnostic detection of disease-associated DNA methylation signatures. Scientific Reports 2017, 7, 13421.
• Schwalbe EC, Lindsey JC, Nakjang S, Crosier S, Smith AJ, Hicks D, Rafiee G, Hill RM, Iliasova A, Stone T, Pizer B, Michalski A, Joshi A, Wharton SB, Jacques TS, Bailey S, Williamson D, Clifford SC. Novel molecular subgroups for clinical classification and outcome prediction in childhood medulloblastoma: a cohort study. The Lancet Oncology 2017, 18(7), 958-971.
• Niklison-Chirou MV, Erngren I, Engskog M, Haglof J, Picard D, Remke M, McPolin PHR, Selby M, Williamson D, Clifford SC, Michod D, Hadjiandreou M, Arvidsson T, Pettersson C, Melino G, Marino S. TAp73 is a marker of glutamine addiction in medulloblastoma. Genes and Development 2017, 31(17), 1738-1753.
• Wong JP, Todd JR, Finetti MA, McCarthy F, Broncel M, Vyse S, Luczynski MT, Crosier S, Ryall KA, Holmes K, Payne LS, Daley F, Wai P, Jenks A, Tanos B, Tan AC, Natrajan RC, Williamson D, Huang PH. Dual Targeting of PDGFR alpha and FGFR1 Displays Synergistic Efficacy in Malignant Rhabdoid Tumors. Cell Reports 2016, 17(5), 1265-1275.
• 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. Combined MYC and P53 Defects Emerge at Medulloblastoma Relapse and Define Rapidly Progressive, Therapeutically Targetable Disease. Cancer Cell 2015, 27(1), 72-84.
• Lindsey JC, Kawauchi D, Schwalbe EC, Solecki DJ, Selby MP, McKinnon PJ, Olson JM, Hayden JT, Grundy RG, Ellison DW, Williamson D, Bailey S, Roussel MF, Clifford SC. Cross-species epigenetics identifies a critical role for VAV1 in SHH subgroup medulloblastoma maintenance. Oncogene 2015, 34(36), 4746-4757.
• Nicholson L, Evans C, Matheson E, Minto L, Keilty C, Sanichar M, Case M, Schwab C, Williamson D, Rainer J, Harrison C, Kofler R, Hall AG, Rednern CPF, Wheaton AD, Irving JAE. Quantitative proteomic analysis reveals maturation as a mechanism underlying glucocorticoid resistance in B lineage ALL and re-sensitization by JNK inhibition. British Journal of Haematology 2015, 171(4), 595–605.
• Gottardo NG, Hansford JR, McGlade JP, Alvaro F, Ashley DM, Bailey S, Baker DL, Bourdeaut F, Cho YJ, Clay M, Clifford SC, Cohn RJ, Cole CH, Dallas PB, Downie P, Doz F, Ellison DW, Endersby R, Fisher PG, Hassall T, Heath JA, Hii HL, Jones DTW, Junckerstorff R, Kellie S, Kool M, Kotecha RS, Lichter P, Laughton SJ, Lee S, McCowage G, Northcott PA, Olson JM, Packer RJ, Pfister SM, Pietsch T, Pizer B, Pomeroy SL, Remke M, Robinson GW, Rutkowski S, Schoep T, Shelat AA, Stewart CF, Sullivan M, Taylor MD, Wainwright B, Walwyn T, Weiss WA, Williamson D, Gajjar A. Medulloblastoma Down Under 2013: a report from the third annual meeting of the International Medulloblastoma Working Group. Acta Neuropathologica 2014, 127(2), 189-201.
• Schwalbe EC, Williamson D, Lindsey JC, Hamilton D, Ryan SL, Megahed H, Garami M, Hauser P, Dembowska-Baginska B, Perek D, Northcott PA, Taylor MD, Taylor RE, Ellison DW, Bailey S, Clifford SC. DNA methylation profiling of medulloblastoma allows robust subclassification and improved outcome prediction using formalin-fixed biopsies. Acta Neuropathologica 2013, 125(3), 359-371.
• Missiaglia E, Williamson D, Chisholm J, Wirapati P, Pierron G, Petel F, Concordet JP, Thway K, Oberlin O, Pritchard-Jones K, Delattre O, Delorenzi M, Shipley J. PAX3/FOXO1 Fusion Gene Status is the Key Prognostic Molecular Marker in Rhabdomyosarcoma and Significantly Improves Current Risk Stratification. Journal of Clinical Oncology 2012, 30(14), 1670-1677.
• Ptasinska A, Assi SA, Mannari D, James SR, Williamson D, Dunne J, Hoogenkamp M, Wu M, Care M, McNeill H, Cauchy P, Cullen M, Tooze RM, Tenen DG, Young BD, Cockerill PN, Westhead DR, Heidenreich O, Bonifer C. Depletion of RUNX1/ETO in t(8;21) AML cells leads to genome-wide changes in chromatin structure and transcription factor binding. Leukemia 2012, 26(8), 1829-1841.
• Ryan SL, Schwalbe EC, Cole M, Lu Y, Lusher ME, Megahed H, O'Toole K, Nicholson SL, Bognar L, Garami M, Hauser P, Korshunov A, Pfister SM, Williamson D, Taylor RE, Ellison DW, Bailey S, Clifford SC. MYC family amplification and clinical risk-factors interact to predict an extremely poor prognosis in childhood medulloblastoma. Acta Neuropathologica 2012, 123(4), 501-513.
• Jones DTW, Jager N, Kool M, Zichner T, Hutter B, Sultan M, Cho YJ, Pugh TJ, Hovestadt V, Stutz AM, Rausch T, Warnatz HJ, Ryzhova M, Bender S, Sturm D, Pleier S, Cin H, Pfaff E, Sieber L, Wittmann A, Remke M, Witt H, Hutter S, Tzaridis T, Weischenfeldt J, Raeder B, Avci M, Amstislavskiy V, Zapatka M, Weber UD, Wang Q, Lasitschka B, Bartholomae CC, Schmidt M, von Kalle C, Ast V, Lawerenz C, Eils J, Kabbe R, Benes V, van Sluis P, Koster J, Volckmann R, Shih D, Betts MJ, Russell RB, Coco S, Tonini GP, Schuller U, Hans V, Graf N, Kim YJ, Monoranu C, Roggendorf W, Unterberg A, Herold-Mende C, Milde T, Kulozik AE, von Deimling A, Witt O, Maass E, Rossler J, Ebinger M, Schuhmann MU, Fruhwald MC, Hasselblatt M, Jabado N, Rutkowski S, von Bueren AO, Williamson D, Clifford SC, McCabe MG, Collins VP, Wolf S, Wiemann S, Lehrach H, Brors B, Scheurlen W, Felsberg J, Reifenberger G, Northcott PA, Taylor MD, Meyerson M, Pomeroy SL, Yaspo ML, Korbel JO, Korshunov A, Eils R, Pfister SM, Lichter P. Dissecting the genomic complexity underlying medulloblastoma. Nature 2012, 488(7409), 100-105.
• Korshunov A, Remke M, Kool M, Hielscher T, Northcott PA, Williamson D, Pfaff E, Witt H, Jones DTW, Ryzhova M, Cho YJ, Wittmann A, Benner A, Weiss WA, von Deimling A, Scheurlen W, Kulozik AE, Clifford SC, Collins VP, Westermann F, Taylor MD, Lichter P, Pfister SM. Biological and clinical heterogeneity of MYCN-amplified medulloblastoma. Acta Neuropathologica 2012, 123(4), 515-527.
• Williamson D, Missiaglia E, deReynies A, Pierron G, Thuille B, Palenzuela G, Thway K, Orbach D, Lae M, Freneaux P, Pritchard-Jones K, Oberlin O, Shipley J, Delattre O. Fusion Gene-Negative Alveolar Rhabdomyosarcoma Is Clinically and Molecularly Indistinguishable From Embryonal Rhabdomyosarcoma. Journal of Clinical Oncology 2010, 28(13), 2151-2158.
• Williamson D, Missiaglia E, de Reyniès A, Pierron G, Thuille B, Palenzuela G, Thway K, Orbach D, Laé M, Fréneaux P, Pritchard-Jones K, Oberlin O, Shipley J, Delattre O. Reply to J.R. Anderson et al. Journal of Clinical Oncology 2010, 28(29), e589-e590.
• Missiaglia E, Williamson D, Chisholm J, Wirapati P, Pierron G, Petel F, Concordet JP, Thway K, Oberlin O, Pritchard-Jones K, Delattre O, Delorenzi M, Shipley J. Questionable Universal Validity of PAX3/FOXO1 Fusion Gene Status As Molecular Marker for Improvement of Risk Stratification in Rhabdomyosarcoma Therapy Reply. JOURNAL OF CLINICAL ONCOLOGY 2012, 30(32), 4040-4041.
• Missiaglia E, Selfe J, Hamdi M, Williamson D, Schaaf G, Fang C, Koster J, Summersgill B, Messahel B, Versteeg R, Pritchard-Jones K, Kool M, Shipley J. Genomic Imbalances in Rhabdomyosarcoma Cell Lines Affect Expression of Genes Frequently Altered in Primary Tumors: An Approach to Identify Candidate Genes Involved in Tumor Development. Genes, Chromosomes & Cancer 2009, 48(6), 455-467.
• Williamson D, Selfe J, Gordon T, Lu YJ, Pritchard-Jones K, Murai K, Jones P, Workman P, Shipley J. Role for amplification and expression of Glypican-5 in rhabdomyosarcoma. Cancer Research 2007, 67(1), 57-65.
• Anderson J, Gibson S, Williamson D, Rampling D, Austin C, Shipley J, Sebire N, Brock P. Rapid and accurate determination of MYCN copy number and 1p deletion in neuroblastoma by quantitative PCR. Pediatric Blood & Cancer 2006, 46(7), 820-824.
• Hanks S, Coleman K, Summersgill B, Messahel B, Williamson D, Pritchard-Jones K, Strefford J, Swansbury J, Plaja A, Shipley J, Rahman N. Comparative genomic hybridization and BUB1B mutation analyses in childhood cancers associated with mosaic variegated aneuploidy syndrome. Cancer Letters 2006, 239(2), 234-238.
• Williamson D, Lu YJ, Fang C, Pritchard-Jones K, Shipley J. Nascent pre-rRNA overexpression correlates with an adverse prognosis in alveolar rhabdomyosarcoma. Genes, Chromosomes & Cancer 2006, 45(9), 839-845.
• Rees H, Williamson D, Papanastasiou A, Jina N, Nabarro S, Shipley J, Anderson J. The MET receptor tyrosine kinase contributes to invasive tumour growth in rhabdomyosarcomas. Growth Factors 2006, 24(3), 197-208.
• Williamson D, Lu YJ, Gordon T, Sciot R, Kelsey A, Fisher C, Poremba C, Anderson J, Pritchard-Jones K, Shipley J. Relationship between MYCN copy number and expression in rhabdomyosarcomas and correlation with adverse prognosis in the alveolar subtype. Journal of Clinical Oncology 2005, 23(4), 880-888.
• Williamson D, Lu YJ, McIntyre A, Summersgill B, Wang RB, Selfe J, Cooper C, Clark J, Shipley J. Comparative genomic hybridisation and comparative expressed sequence hybridisation as complements to microarray analyses of tumours. Mutagenesis 2004, 19(6), 509-509.
• Lu YJ, Williamson D, Wang R, Summersgill B, Rodriguez S, Rogers S, Pritchard-Jones K, Campbell C, Shipley J. Expression profiling targeting chromosomes for tumor classification and prediction of clinical behavior. Genes, Chromosomes & Cancer 2003, 38(3), 207-214.
• Wickramasinghe CM, Domaschenz R, Amagase Y, Williamson D, Missiaglia E, Shipley J, Murai K, Jones PH. HES6 enhances the motility of alveolar rhabdomyosarcoma cells. Experimental Cell Research 2013, 319(1), 103-112.
• Lu YJ, Williamson D, Clark J, Wang R, Tiffin N, Skelton L, Gordon T, Williams R, Allan B, Jackman A, Cooper C, Pritchard-Jones K, Shipley J. Comparative expressed sequence hybridization to chromosomes for tumor classification and identification of genomic regions of differential gene expression. Proceedings of the National Academy of Sciences of the United States of America 2001, 98(16), 9197-9202.