Research groups

Translational Pediatric Sarcoma Research

Translational Pediatric Sarcoma Research

The mission of the division of "Translational Pediatric Sarcomas Research", which corresponds to the DKFZ division of the same name, is to improve treatment options for children and adolescents affected by sarcomas. We aim at uncovering disease mechanisms that can be used diagnostically and therapeutically to improve the long-term chances of recovery of our young patients. The focus lies on new methods that are essential for correct diagnosis and the choice of the best possible therapy. We also investigate less aggressive therapies and new approaches to overcome drug resistance of tumors. In this regard, one special objective is to decipher the interactions between acquired mutations and innate natural variants of the genome, which can play a decisive role in the development and progression of cancer, particularly in Ewing sarcoma.

We aim at developing novel therapeutic strategies based on new insights into the molecular mechanisms of disease following two major lines of research (see research areas). Our investigations start with the analysis of the patients’ tumors in situ, followed by studying patient-derived cell lines using a wide variety of in silico, in vitro, and in vivo techniques.

The division is supported by the Barbara und Wilfried Mohr Stiftung.

Translational spectrum of methods

Histology, omics‘-analyses, preclinical models, correlation with clinical data

Research areas

Dominant oncogenes often hijack or interfere with developmental pathways thereby conferring a considerable growth advantage to tumor cells. We are interested in the mechanisms through which oncogenes arrest sarcoma cells in a lineage-specific, early-committed but yet largely undifferentiated state via deregulation of key developmental pathways, and how they cooperate with them to promote tumorigenesis and cancer progression.

Primary and/or secondary resistance to conventional chemotherapeutic drugs is a frequent event in pediatric sarcoma. Chemo-resistance is a highly specific process in which tumors become resistant to certain drugs while maintaining (limited) susceptibility toward others. Underlying to this resistance is considerable plasticity due to intra-tumor heterogeneity, which enables the adaptation to therapeutic stress on the clonal and sub-clonal level. We strive for illuminating the genetic basis and biological mechanisms of tumor-heterogeneity and aim at identifying novel biomarkers for individualized risk-stratification, prediction of treatment response, and to indicate which targeted therapeutics may help overcoming resistance to conventional (chemo)therapeutics.

 

Team

  • PD Dr. Dr. Thomas Grünewald (Division Head)
  • Dr. Florencia Cidre-Aranaz (Project Leader & Deputy Division Head)
  • Dr. Laura Romero-Pérez (PostDoc)
  • Julian Musa (Physician Scientist)
  • Katharina Ceranski (PhD/MD Thesis Student)
  • Anna Ehlers (PhD/MD Thesis Student)
  • Cornelius Funk (PhD/MD Thesis Student)
  • Martha Julia Carreño Gonzalez (PhD/MD Thesis Studentin)
  • Jia Xiang Jin (PhD/MD Thesis Student)
  • Jing Li (PhD/MD Thesis Student)
  • Endrit Vinca (PhD/MD Thesis Student)
  • Malenka Zimmermann (PhD/MD Thesis Student)
  • Stefanie Kutschmann (Technician)
  • Felina Zahnow (Technician)
  • Gabriele Meyer (Administration)

PD Dr. Dr. Thomas Grünewald

Head of Division "Translational Pediatric Sarcoma Research"

Postal address:

Deutsches Krebsforschungszentrum (DKFZ)
Div. Translational Pediatric Sarcoma Research/B410
Im Neuenheimer Feld 280
69120 Heidelberg

 

Publications

Selected Publications

  1. Marchetto A, Ohmura S, Orth MF, Knott MML, Colombo MV, Arrigoni C, Bardinet V, Saucier D, Wehweck FS, Li J, Stein S, Gerke JS, Baldauf MC, Musa J, Dallmayer M, Romero-Pérez L, Hölting TLB, Amatruda JF, Cossarizza A, Henssen AG, Kircher T,Moretti M, Cidre-Aranaz F, Sannino G, Grünewald TGP (2020). Oncogenic hijacking of a developmental transcription factor evokes vulnerability toward oxidative stress in Ewing sarcoma. Nat Commun 2020 May;11(1):2423
  2. Musa J, Cidre-Aranaz F, Aynaud MM, Orth MF, Knott MML, Mirabeau M, Mazor G, Varon M, Hölting TLB, Grossetête S, Gartlgruber M, Surdez D, Gerke JS, Ohmura S, Marchetto A, Dallmayer M, Baldauf MC, Stein S, Sannino G, Li J, Romero-Pérez L, Westermann F, Hartmann W, Dirksen U, Gymrek M, Anderson ND, Shlien A, Rotblat B, Kirchner T, Delattre O, Grünewald TG (2019). Cooperation of cancer drivers with germline regulatory variants shapes clinical outcomes. Nat Commun 2019 Sept;10(1):4128
  3. Machiela MJ, Grünewald TG, Surdez D, Reynaud S, Mirabeau O, Karlins E, Rubio RA, Zaidi S, Grossetete-Lalami S, Ballet S, Lapouble E, Laurence V, Michon J, Pierron G, Kovar H, Gaspar N, Kontny U, González-Neira A, Picci P, Alonso J, Patino-Garcia A, Corradini N, Bérard PM, Freedman ND, Rothman N, Dagnall CL, Burdett L, Jones K, Manning M, Wyatt K, Zhou W, Yeager M, Cox DG, Hoover RN, Khan J, Armstrong GT, Leisenring WM, Bhatia S, Robison LL, Kulozik AE, Kriebel J, Meitinger T, Metzler M, Hartmann W, Strauch K, Kirchner T, Dirksen U, Morton LM, Mirabello L, Tucker MA, Tirode F, Chanock SJ, Delattre O (2018). Genome-wide association study identifies multiple new loci associated with Ewing sarcoma susceptibility. Nat Commun 2018 Aug;9(1):3184
  4. Grünewald TG*, Cidre-Aranaz F*, Surdez D, Tomazou EM, de Alava E, Kovar H, Sorensen PH, Delattre O, Dirksen U (2018). Ewing sarcoma. Nat Rev Dis Primers 2018 4(1):5
  5. Grünewald TG, Bernard V, Gilardi-Hebenstreit P, Raynal V, Surdez D, Aynaud MM, Mirabeau O, Cidre-Aranaz F, Tirode F, Zaidi S, Perot G, Jonker AH, Lucchesi C, Le Deley MC, Oberlin O, Marec-Bérard P, Véron AS, Reynaud S, Lapouble E, Boeva V, Rio Frio T, Alonso J, Bhatia S, Pierron G, Cancel-Tassin G, Cussenot O, Cox DG, Morton LM, Machiela MJ, Chanock SJ, Charnay P, Delattre O (2015). Chimeric EWSR1-FLI1 regulates the Ewing sarcoma susceptibility gene EGR2 via a GGAA microsatellite. Nat Genet 2015 Sep;47(9):1073-8

Awards, Prizes, Scholarships

  • Thomas Grünewald receives the Rudolf-Virchow-Prize 2020. Press Release (in German only)
  • Cornelius Funk receives a scholarship as part of the Mildred Scheel doctoral program of the German Cancer Aid.