The Schulte Lab

The goal of the Schulte Research Lab is the development of targeted and personalized treatment strategies and novel therapies for patients with neuroblastoma and other childhood tumors. In this context, understanding the pathogenesis and tumor biology is the foundation of any rational therapy.

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Research of the Schulte Lab

Investigating primary and relapse tumors as well as tumor model systems, we seek to identify key factors of tumor pathogenesis, tumor progression and tumor evolution. Of special interest is the role of epigenetics and non-coding RNAs in these processes. The research strategy of our interdisciplinary team includes multi-omics and wet lab approaches. Concepts identified in high-throughput analyses are validated in vitro and in vivo. To this end, we use cell culture model systems, patient-derived tumor xenografts (PDX) in immuno-deficient mice and genetically engineered mouse models (GEMMs).

We join academic and industry partners in the development of novel compounds for promising targets. Embedded in the clinical and research network at the Charité University Medicine, our team's objective is to identify target structures of clinical and therapeutic relevance, and eventually initiate as well as conduct early phase clinical trials. We provide a platform for trial setups, by simulating therapeutic intervention in mice, identifying predictive and pharmacodynamic biomarkers, suggesting effective drug combinations and analyzing potential resistance mechanisms.

The Schulte Lab is currently working on the following research projects

  • identifying the role of circular RNAs in neuroblastoma
  • identifying the role of the Hippo-YAP pathway in neuroblastoma
  • characterizing key players in neuroblastoma pathogenesis using next-generation sequencing approaches
  • deciphering the role of MCPH-genes in embryonal tumors
  • optimizing Minimal Residual Disease (MRD) detection for neuroblastoma diagnostics
  • developing new mouse models of embryonal tumors

The most important publications of the Schulte Lab

(For a complete publication list, please click here)

Henssen A.G., Althoff K, Odersky A, Beckers A, Koche R, Speleman F, Schaefer S, Bell E, Nortmeyer M, Westermann F, De Preter K, Florin A, Heukamp L, Spruessel A, Astrahanseff K, Lindner S, Solomentsew N, Schramm A, Astorgues-Xerri L, Riveiro ME, Eggert A, Cvitkovic E. Schulte JH. Targeting MYCN-driven transcription by BET-bromodomain inhibition. Clin Cancer Res. 2015 Dec 2. Pubmed

Peifer M, Hertwig F, Roels F, Dreidax D, Gartlgruber M, Menon R, Krämer A, Roncaioli JL, Sand F, Heuckmann JM, Ikram F, Schmidt R, Ackermann S, Engesser A, Kahlert Y, Vogel W, Altmüller J, Nürnberg P, Thierry-Mieg J, Thierry-Mieg D, Mariappan A, Heynck S, Mariotti E, Henrich KO, Gloeckner C, Bosco G, Leuschner I, Schweiger MR, Savelyeva L, Watkins SC, Shao C, Bell E, Höfer T, Achter V, Lang U, Theissen J, Volland R, Saadati M, Eggert A, de Wilde B, Berthold F, Peng Z, Zhao C, Shi L, Ortmann M, Büttner R, Perner S, Hero B, Schramm A, Schulte JH, Herrmann C, O'Sullivan RJ, Westermann F, Thomas RK, Fischer M. Telomerase activation by genomic rearrangements in high-risk neuroblastoma. Nature. 2015 Oct 29;526(7575):700-4. Pubmed

Eleveld TF, Oldridge DA, Bernard V, Koster J, Daage LC, Diskin SJ, Schild L, Bentahar NB, Bellini A, Chicard M, Lapouble E, Combaret V, Legoix-Né P, Michon J, Pugh TJ, Hart LS, Rader J, Attiyeh EF, Wei JS, Zhang S, Naranjo A, Gastier-Foster JM, Hogarty MD, Asgharzadeh S, Smith MA, Guidry Auvil JM, Watkins TB, Zwijnenburg DA, Ebus ME, van Sluis P, Hakkert A, van Wezel E, van der Schoot CE, Westerhout EM, Schulte JH, Tytgat GA, Dolman ME, Janoueix-Lerosey I, Gerhard DS, Caron HN, Delattre O, Khan J, Versteeg R, Schleiermacher G, Molenaar JJ, Maris JM. Relapsed neuroblastomas show frequent RAS-MAPK pathway mutations. Nat Genet. 2015 Aug;47(8):864-71. Pubmed

Schramm A, Köster J, Assenov Y, Althoff K, Peifer M, Mahlow E, Odersky A, Beisser D, Ernst C, Henssen A.G., Stephan H, Schröder C, Heukamp L, Engesser A, Kahlert Y, Theissen J, Hero B, Roels F, Altmüller J, Nürnberg P, Astrahantseff K, Gloeckner C, De Preter K, Plass C, Lee S, Lode HN, Henrich KO, Gartlgruber M, Speleman F, Schmezer P, Westermann F, Rahmann S, Fischer M, Eggert A, Schulte JH. Mutational dynamics between primary and relapse neuroblastomas. Nat Genet. 2015 Aug;47(8):872-7. Pubmed

Althoff K, Beckers A, Bell E, Nortmeyer M, Thor T, Sprüssel A, Lindner S, De Preter K, Florin A, Heukamp LC, Klein-Hitpass L, Astrahantseff K, Kumps C, Speleman F, Eggert A, Westermann F, Schramm A, Schulte JH. A Cre-conditional MYCN-driven neuroblastoma mouse model as an improved tool for preclinical studies. Oncogene. 2015 Jun;34(26):3357-68. Pubmed

Heukamp LC, Thor T, Schramm A, De Preter K, Kumps C, De Wilde B, Odersky A, Peifer M, Lindner S, Spruessel A, Pattyn F, Mestdagh P, Menten B, Kuhfittig-Kulle S, Künkele A, König K, Meder L, Chatterjee S, Ullrich RT, Schulte S, Vandesompele J, Speleman F, Büttner R, Eggert A, Schulte JH. Targeted expression of mutated ALK induces neuroblastoma in transgenic mice. Sci Transl Med. 2012; Jul 4;4(141):141ra91. Pubmed

Nittner D, Lambertz I, Clermont F, Mestdagh P, Köhler C, Nielsen SJ, Jochemsen A, Speleman F, Vandesompele J, Dyer MA, Schramm A, Schulte JH, Marine JC. Synthetic lethality between Rb, p53 and Dicer or miR-17-92 in retinal progenitors suppresses retinoblastoma formation. Nat Cell Biol. 2012 Sep;14(9):958-65. Pubmed

Molenaar JJ, Domingo-Fernández R, Ebus ME, Lindner S, Koster J, Drabek K, Mestdagh P, van Sluis P, Valentijn LJ, van Nes J, Broekmans M, Haneveld F, Volckmann R, Bray I, Heukamp L, Sprüssel A, Thor T, Kieckbusch K, Klein-Hitpass L, Fischer M, Vandesompele J, Schramm A, van Noesel MM, Varesio L, Speleman F, Eggert A, Stallings RL, Caron HN, Versteeg R, Schulte JH. LIN28B induces neuroblastoma and enhances MYCN levels via let-7 suppression. Nat Genet. 2012; Nov;44(11):1199-206. Pubmed

Schulte JH, Marschall T, Martin M, Rosenstiel P, Mestdagh P, Schlierf S, Thor T, Vandesompele J, Eggert A, Schreiber S, Rahmann S, Schramm A. Deep sequencing reveals differential expression of microRNAs in favorable versus unfavorable neuroblastoma. Nucleic Acids Res. 2010 Sep;38(17):5919-28. Pubmed

Schulte JH, Lim S, Schramm A, Friedrichs N, Koster J, Versteeg R, Ora I, Pajtler K, Klein-Hitpass L, Kuhfittig-Kulle S, Metzger E, Schüle R, Eggert A, Buettner R, Kirfel J. Lysine-specific demethylase 1 is strongly expressed in poorly differentiated neuroblastoma: implications for therapy. Cancer Res. 2009 Mar 1;69(5):2065-71. Pubmed



Current funding

The Schulte Lab is currently part of four international research consortia whose aim it is to decipher the key factors of neuroblastoma pathogenesis by employing systems level analysis. Another purpose of our research in these consortia is the exploitation of systems medicine for therapy optimization of high-risk neuroblastoma patients.