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Junior Research Group leader: Pediatric Neuro-Oncogenomics

Prof. Dr. Marc Remke
Department of Pediatric Oncology, Hematology and Clinical Immunology
German Cancer Consortium (DKTK)
University Hospital Düsseldorf
Moorenstraße 5
40225 Düsseldorf

Children with brain tumors are often treated with neurosurgery, radiotherapy and chemotherapy. Brain tumors remain the number one cause of death in children diagnosed with cancer despite improved multimodal therapy approaches. Our main aim is to gain a better understanding of the underlying biology causing tumorigenesis and aggressiveness of these tumors. This is necessary to improve treatment approaches and develop novel therapy options.

Our strategy is based on two complimentary approaches:

  • Personalized Therapy: By incorporating clinical criteria and biological research results, we can better define individual risk profiles of children with brain tumors. Genome-wide analyses platforms (including next-generation sequencing and mass spectrometry) allow us to identify alterations linked to prognosis. A specific focus here lies in the discovery of long non-coding RNAs with highly conserved temporo-spatial expression patterns pinpointing to the cell of origin of distinct tumor entities, and holding great promise as prognostic biomarkers.
  • Targeted Therapy: To selectively target tumor cells, we focus on the biologically distinct features of tumors in comparison to normal tissue. Functional genome studies support our genome-wide analyses and give us mechanistic insights to refine targeted therapy formats and eventually identify novel drugs for clinical trials. To this end, we have established an automated drug screening pipeline allowing the standardized evaluation of several hundred established anti-cancer drugs and targeted agents currently tested in phase 3 or 4 clinical trials. We utilize this platform to determine drug response profiles dependent on mutational signatures to identify predictive biomarkers.

We strongly believe that pediatric neoplasias may serve as ideal models to study cancer-specific perturbations as the mutational landscape is less complex compared to most of their adult counterparts. Thus, we plan to utilize the functional networks identified in pediatric brain tumors to provide a better understanding of the complex interaction of oncogenic pathways in adult cancers. Such insights will be essential, for example, in identifying patient cohorts across all age groups that will benefit from selected targeted therapeutic agents to guide clinical decision making in the future.

The 10 most important peer-reviewed publications:
  1. Pfister S*, Janzarik WG*, Remke M*, Ernst A, Werft W, Becker N, Toedt G, Wittmann A, Kratz C, Olbrich H, Ahmadi R, Thieme B, Joos S, Radlwimmer B, Kulozik A, Pietsch T, Herold-Mende C, Gnekow A, Reifenberger G, Korshunov A, Scheurlen W, Omran H, Lichter P. BRAF gene duplication constitutes a mechanism of MAPK pathway activation in low-grade astrocytomas. J Clin Invest 2008 May;118(5):1739-49. doi: 10.1172/JCI33656. PubMed
  2. Remke M*, Hielscher T, Korshunov A, Northcott PA, Bender S, Kool M, Westermann F, Benner A, Cin H, Ryzhova M, Sturm D, Witt H, Haag D, Toedt G, Wittmann A, Schottler A, von Bueren AO, von Deimling A, Rutkowski S, Scheurlen W, Kulozik AE, Taylor MD, Lichter P, Pfister SM. FSTL5 is a marker of poor prognosis in non-WNT/non-SHH medulloblastoma. J Clin Oncol 2011 Oct 10;29(29):3852-61. doi: 10.1200/JCO.2011.36.2798. Epub 2011 Sep 12. PubMed
  3. Remke M, Hielscher T, Northcott PA, Witt H, Ryzhova M, Wittmann A, Benner A, von Deimling A, Scheurlen W, Perry A, Croul S, Kulozik AE, Lichter P, Taylor MD, Pfister SM, Korshunov A. Adult medulloblastoma comprises three major molecular variants. J Clin Oncol 2011 Jul 1;29(19):2717-23. doi: 10.1200/JCO.2011.34.9373. Epub 2011 May 31. PubMed
  4. Leprivier G, Remke M, Rotblat B, Dubuc A, Mateo AR, Kool M, Agnihotri S, El-Naggar A, Yu B, Somasekharan SP, Faubert B, Bridon G, Tognon CE, Mathers J, Thomas R, Li A, Barokas A, Kwok B, Bowden M, Smith S, Wu X, Korshunov A, Hielscher T, Northcott PA, Galpin JD, Ahern CA, Wang Y, McCabe MG, Collins VP, Jones RG, Pollak M, Delattre O, Gleave ME, Jan E, Pfister SM, Proud CG, Derry WB, Taylor MD, Sorensen PH. The eEF2 kinase confers resistance to nutrient deprivation by blocking translation elongation. Cell 2013 May 23;153(5):1064-79. doi: 10.1016/j.cell.2013.04.055. PubMed
  5. Remke M, Ramaswamy V, Peacock J, Shih DJ, Koelsche C, Northcott PA, Hill N, Cavalli FM, Kool M, Wang X, Mack SC, Barszczyk M, Morrissy AS, Wu X, Agnihotri S, Luu B, Jones DT, Garzia L, Dubuc AM, Zhukova N, Vanner R, Kros JM, French PJ, Van Meir EG, Vibhakar R, Zitterbart K, Chan JA, Bognar L, Klekner A, Lach B, Jung S, Saad AG, Liau LM, Albrecht S, Zollo M, Cooper MK, Thompson RC, Delattre OO, Bourdeaut F, Doz FF, Garami M, Hauser P, Carlotti CG, Van Meter TE, Massimi L, Fults D, Pomeroy SL, Kumabe T, Ra YS, Leonard JR, Elbabaa SK, Mora J, Rubin JB, Cho YJ, McLendon RE, Bigner DD, Eberhart CG, Fouladi M, Wechsler-Reya RJ, Faria CC, Croul SE, Huang A, Bouffet E, Hawkins CE, Dirks PB, Weiss WA, Schuller U, Pollack IF, Rutkowski S, Meyronet D, Jouvet A, Fevre-Montange M, Jabado N, Perek-Polnik M, Grajkowska WA, Kim SK, Rutka JT, Malkin D, Tabori U, Pfister SM, Korshunov A, von Deimling A, Taylor MD. TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma. Acta Neuropathol 2013 Dec;126(6):917-29. doi: 10.1007/s00401-013-1198-2. Epub 2013 Oct 31. PubMed
  6. Vanner RJ, Remke M, Gallo M, Selvadurai HJ, Coutinho F, Lee L, Kushida M, Head R, Morrissy S, Zhu X, Aviv T, Voisin V, Clarke ID, Li Y, Mungall AJ, Moore RA, Ma Y, Jones SJ, Marra MA, Malkin D, Northcott PA, Kool M, Pfister SM, Bader G, Hochedlinger K, Korshunov A, Taylor MD, Dirks PB. Quiescent sox2(+) cells drive hierarchical growth and relapse in sonic hedgehog subgroup medulloblastoma. Cancer Cell 2014 Jul 14;26(1):33-47. doi: 10.1016/j.ccr.2014.05.005. Epub 2014 Jun 19. PubMed
  7. Ramaswamy V*#, Remke M*#, Bouffet E, Bailey S, Clifford SC, Doz F, Kool M, Dufour C, Vassal G, Milde T, Witt O, von Hoff K, Pietsch T, Northcott PA, Gajjar A, Robinson GW, Padovani L, Andre N, Massimino M, Pizer B, Packer R, Rutkowski S, Pfister SM, Taylor MD, Pomeroy SL. Risk stratification of childhood medulloblastoma in the molecular era: the current consensus. Acta Neuropathol2016 Jun;131(6):821-31. doi: 10.1007/s00401-016-1569-6. Epub 2016 Apr 4. PubMed
  8. Morrissy AS*, Cavalli FMG*, Remke M*, Ramaswamy V, Shih DJH, Holgado BL, Farooq H, Donovan LK, Garzia L, Agnihotri S, Kiehna EN, Mercier E, Mayoh C, Papillon-Cavanagh S, Nikbakht H, Gayden T, Torchia J, Picard D, Merino DM, Vladoiu M, Luu B, Wu X, Daniels C, Horswell S, Thompson YY, Hovestadt V, Northcott PA, Jones DTW, Peacock J, Wang X, Mack SC, Reimand J, Albrecht S, Fontebasso AM, Thiessen N, Li Y, Schein JE, Lee D, Carlsen R, Mayo M, Tse K, Tam A, Dhalla N, Ally A, Chuah E, Cheng Y, Plettner P, Li HI, Corbett RD, Wong T, Long W, Loukides J, Buczkowicz P, Hawkins CE, Tabori U, Rood BR, Myseros JS, Packer RJ, Korshunov A, Lichter P, Kool M, Pfister SM, Schuller U, Dirks P, Huang A, Bouffet E, Rutka JT, Bader GD, Swanton C, Ma Y, Moore RA, Mungall AJ, Majewski J, Jones SJM, Das S, Malkin D, Jabado N, Marra MA, Taylor MD. Spatial heterogeneity in medulloblastoma. Nat Genet 2017 May;49(5):780-788. doi: 10.1038/ng.3838. Epub 2017 Apr 10. PubMed
  9. Cavalli FMG*, Remke M*, Rampasek L, Peacock J, Shih DJH, Luu B, Garzia L, Torchia J, Nor C, Morrissy AS, Agnihotri S, Thompson YY, Kuzan-Fischer CM, Farooq H, Isaev K, Daniels C, Cho BK, Kim SK, Wang KC, Lee JY, Grajkowska WA, Perek-Polnik M, Vasiljevic A, Faure-Conter C, Jouvet A, Giannini C, Nageswara Rao AA, Li KKW, Ng HK, Eberhart CG, Pollack IF, Hamilton RL, Gillespie GY, Olson JM, Leary S, Weiss WA, Lach B, Chambless LB, Thompson RC, Cooper MK, Vibhakar R, Hauser P, van Veelen MC, Kros JM, French PJ, Ra YS, Kumabe T, Lopez-Aguilar E, Zitterbart K, Sterba J, Finocchiaro G, Massimino M, Van Meir EG, Osuka S, Shofuda T, Klekner A, Zollo M, Leonard JR, Rubin JB, Jabado N, Albrecht S, Mora J, Van Meter TE, Jung S, Moore AS, Hallahan AR, Chan JA, Tirapelli DPC, Carlotti CG, Fouladi M, Pimentel J, Faria CC, Saad AG, Massimi L, Liau LM, Wheeler H, Nakamura H, Elbabaa SK, Perezpena-Diazconti M, Chico Ponce de Leon F, Robinson S, Zapotocky M, Lassaletta A, Huang A, Hawkins CE, Tabori U, Bouffet E, Bartels U, Dirks PB, Rutka JT, Bader GD, Reimand J, Goldenberg A, Ramaswamy V, Taylor MD. Intertumoral Heterogeneity within Medulloblastoma Subgroups. Cancer Cell 2017 Jun 12;31(6):737-754.e6. doi: 10.1016/j.ccell.2017.05.005. PubMed
  10. Forget A#, Martignetti L, Puget S, Calzone L, Brabetz S, Picard D, Montagud A, Liva S, Sta A, Dingli F, Arras G, Rivera J, Loew D, Besnard A, Lacombe J, Pagès M, Varlet P, Dufour C, Yu H, Mercier AL, Indersie E, Chivet A, Leboucher S, Sieber L, Beccaria K, Gombert M, Meyer FD, Qin N, Bartl J, Chavez L, Okonechnikov K, Sharma T, Thatikonda V, Bourdeaut F, Pouponnot C, Ramaswamy V, Korshunov A, Borkhardt A, Reifenberger G, Poullet P, Taylor MD, Kool M, Pfister SM, Kawauchi D#, Barillot E#, Remke M#, Ayrault O#. Aberrant ERBB4-SRC Signaling as a Hallmark of Group 4 Medulloblastoma Revealed by Integrative Phosphoproteomic Profiling. Cancer Cell. 2018 Sep 10;34(3):379-395.e7. doi: 10.1016/j.ccell.2018.08.002. PubMed


* shared first authorship
# corresponding author

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