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 Universitätsmedizin, 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
- The role and therapeutic potential of the IGF2BP1-MYCN oncogenic network in neuroblastoma
- optimizing Minimal Residual Disease (MRD) detection for neuroblastoma diagnostics
- developing new mouse models of embryonal tumors
The most important publications of the Schulte Lab
click here (for a complete publication list)
Fischer M, Moreno L, Ziegler DS, Marshall LV, Zwaan CM, Irwin MS, Casanova M, Sabado C, Wulff B, Stegert M, Wang L, Hurtado FK, Branle F, Geoerger B*, Schulte JH*. Ceritinib in paediatric patients with anaplastic lymphoma kinase (ALK)-positive malignancies: a phase 1, open-label, dose-escalation study. Lancet Oncology. 2021 Nov 12:S1470-2045(21)00536-2. doi: 10.1016/S1470-2045(21)00536-2. Epub ahead of print. PMID: 34780709. Pubmed
Szymansky A, Kruetzfeldt LM, Heukamp LC, Hertwig F, Theissen J, Deubzer HE, Willing EM, Menon R, Fuchs S, Thole T, Schulte S, Schmelz K, Künkele A, Lang P, Fuchs J, Eggert A, Eckert C, Fischer M, Henssen AG, Rodriguez-Fos E, Schulte JH. Neuroblastoma Risk Assessment and Treatment Stratification with Hybrid Capture-Based Panel Sequencing. J Pers Med. 2021 Jul 22;11(8):691. doi: 10.3390/jpm11080691. PMID: 34442335; PMCID: PMC8398598. Pubmed
Koche RP, Rodriguez-Fos E, Helmsauer K, Burkert M, MacArthur IC, Maag J, Chamorro R, Munoz-Perez N, Puiggròs M, Dorado Garcia H, Bei Y, Röefzaad C, Bardinet V, Szymansky A, Winkler A, Thole T, Timme N, Kasack K, Fuchs S, Klironomos F, Thiessen N, Blanc E, Schmelz K, Künkele A, Hundsdörfer P, Rosswog C, Theissen J, Beule D, Deubzer H, Sauer S, Toedling J, Fischer M, Hertwig F, Schwarz RF, Eggert A, Torrents D*, Schulte JH*, Henssen AG*. Extrachromosomal circular DNA drives oncogenic genome remodeling in neuroblastoma. Nat Genet. 2020 Jan;52(1):29-34. doi: 10.1038/s41588-019-0547-z. Pubmed
Ackermann S, Cartolano M, Hero B, Welte A, Kahlert Y, Roderwieser A, Bartenhagen C, Walter E, Gecht J, Kerschke L, Volland R, Menon R, Heuckmann JM, Gartlgruber M, Hartlieb S, Henrich KO, Okonechnikov K, Altmüller J, Nürnberg P, Lefever S, de Wilde B, Sand F, Ikram F, Rosswog C, Fischer J, Theissen J, Hertwig F, Singhi AD, Simon T, Vogel W, Perner S, Krug B, Schmidt M, Rahmann S, Achter V, Lang U, Vokuhl C, Ortmann M, Büttner R, Eggert A, Speleman F, O'Sullivan RJ, Thomas RK, Berthold F, Vandesompele J, Schramm A, Westermann F*, Schulte JH*, Peifer M*, Fischer M*. A mechanistic classification of clinical phenotypes in neuroblastoma. Science. 2018 Dec 7;362(6419):1165-1170. doi: 10.1126/science.aat6768. PMID: 30523111; PMCID: PMC7875194. Pubmed
Henssen AG, Reed C, Jiang E, Garcia HD, von Stebut J, MacArthur IC, Hundsdoerfer P, Kim JH, de Stanchina E, Kuwahara Y, Hosoi H, Ganem NJ, Dela Cruz F, Kung AL, Schulte JH, Petrini JH, Kentsis A. Therapeutic targeting of PGBD5-induced DNA repair dependency in pediatric solid tumors. Sci Transl Med. 2017 Nov 1;9(414). Pubmed
Arnhold, V., K. Schmelz, J. Proba, A. Winkler, J. Wünschel, J. Toedling, H.E. Deubzer, A. Künkele, A. Eggert, J.H. Schulte, P. Hundsdoerfer (2017). Reactivating TP53 signaling by the novel MDM2 inhibitor DS-3032b as a therapeutic option for high-risk neuroblastoma. Oncotarget 9, 2304-19. Pubmed
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.
