Jarno Drost Group

Molecular dissection of childhood solid tumors

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Our Focus

Although survival rates for children with cancer have increased in recent decades, cancer is still the leading cause of disease-related deaths in children. Survivors suffer from side effects of the, in most cases, intensive treatment regimens. Hence, there is an urgent need to develop new therapies. However, therapeutic innovation is hampered by the lack of cell models representative of native tumour tissue. My lab pioneers the use of organoid technology for paediatric cancer research.   

  
Many childhood tumours originate in the developing fetes. They are likely caused by a block in processes driving lineage-specification and differentiation. In most cases, the cells from which the tumours originate are only present during short, specific time-windows in development, which makes it challenging to identify the processes initiating and driving tumorigenesis. We aim to identify the origin of childhood cancer and to increase our understanding of the processes that underpin their development. To this end, we take a multi-disciplinary approach making use of our unique in vitro models, access to unique patient material, in vivo orthotopic xenograft models, as well as state-of-the-art (single-cell) omics and lineage tracing technologies.  Ultimately, we aim to develop new, less toxic therapies to treat children with cancer.  

About Jarno Drost

My Research

Jarno Drost obtained his Master’s degree in Biomedical Sciences cum laude in 2005 from the Free University in Amsterdam. He received his PhD from the Erasmus University Rotterdam for his work on the identification of new tumor suppressor genes in the P53 pathway in the research group of Reuven Agami at the Netherlands Cancer Institute in Amsterdam.

Subsequently, Jarno joined the group of Hans Clevers at the Hubrecht Institute for his postdoctoral training where he exploited the organoid technology for cancer research. He developed colorectal cancer (CRC) progression models by introducing combinations of the most commonly mutated CRC genes in human small intestinal and colonic organoids using CRISPR/Cas9 genome editing. He used these models to study multistep tumorigenesis. For his work he received an NWO/Veni fellowship and the Dr. Patrick Hanlo Award for best postdoctoral researcher of the Hubrecht Institute.

In November 2016, he became a group leader at the Princess Máxima Center for pediatric oncology. His group studies the molecular alterations underlying pediatric solid tumors and uses novel pre-clinical model systems to identify therapeutic targets. He was granted a Bas Mulder young investigator award from the Dutch Cancer Society (KWF), the ERC Starting and NWO-Vidi grants, and the AACR St. Baldrick’s career development award for emerging leaders in the field of pediatric oncology.

Awards
  • 2021: NWO-Vidi grant

  • 2021: Achieved tenure at Princess Máxima Center for Pediatric Oncology

  • 2020: AACR St. Baldrick’s career development award

  • 2019: European Research Council (ERC) Starting Grant

  • 2017: Dr. Patrick Hanlo Award for best postdoctoral researcher of the Hubrecht Institute

  • 2016: Bas Mulder young investigator award from the Dutch Cancer Society (KWF)

  • 2014: NWO (Netherlands organization for scientific research) VENI award

Key Publications
  1. Meister, M.T., Groot Koerkamp, M.J.A., de Souza, T., Breunis, W.B., Frazer-Mendelewska, E., Brok, M., DeMartino, J., Manders, F., Calandrini, C., Kerstens, H.H.D., Janse, A., Dolman, M.E.M., Eising, S., Langenberg, K.P.S., van Tuil, M., Knops, R.R.G., van Scheltinga, S.T., Hiemcke-Jiwa, L.S., Flucke, U., Merks, J.H.M., van Noesel, M.M., Tops, B.B.J., Hehir-Kwa, J.Y., Kemmeren, P., Molenaar, J.J., van de Wetering, M., van Boxtel, R., Drost, J.#, Holstege, F.C.P#. Mesenchymal tumor organoid models recapitulate rhabdomyosarcoma subtypes. EMBO Molecular Medicine 2022 Aug 2; e16001. doi: 10.15252/emmm.202216001.

  2. Calandrini, C., van Hooff, S.R., Paassen, I., Ayyildiz, D., Derakhshan, S., Dolman, M.E.M., Langenberg, K.P.S., van de Ven, M., de Heus, C., Liv, N., Kool, M., de Krijger, R.R., Tytgat, G.A.M., van den Heuvel-Eibrink, M.M., Molenaar, J.J., Drost, J. Organoid-based drug screening reveals neddylation as therapeutic target for malignant rhabdoid tumors. Cell Reports 2021 Aug 24; 36(8):109568. doi: 10.1016/j.celrep.2021.109568.

  3. Young, M.D.*, Mitchell, T.J.*, Custers, L.*, Margaritis, T., Morales-Rodriguez, F., Kwakwa, K., Khabirova, E., Kildisiute, G., Oliver, T.R.W., de Krijger, R.R., van den Heuvel-Eibrink, M.M., Comitani, F., Piapi, A., Bugallo-Blanco, E., Thevanesan, C., Burke, C., Prigmore, E., Ambridge, K., Roberts, K., Vieira Braga, F.A., Coorens, T.H.H., Del Valle, I., Wilbrey-Clark, A., Mamanova, L., Stewart, G.D., Gnanapragasam, V.J., Rampling, D., Sebire, N., Coleman, N., Hook, L., Warren, A., Haniffa, M., Kool, M., Pfister, S.M., Achermann, J.C., He, X., Barker, R.A., Shlien, A., Bayraktar, O.A, Teichmann, S., Holstege, F.C., Meyer, K.B., Drost, J.#, Straathof, K.#, Behjati, S.#. Single cell derived mRNA signals across human kidney tumors. Nature Communications 2021 Jun 23; 12(1):3896. doi: 10.1038/s41467-021-23949-5.

  4. Custers, L.*, Khabirova, E.*, Coorens, T.H.H.*, Oliver, T.R.W., Calandrini, C., Young, M.D., Vieira Braga, F.A., Ellis, P., Mamanova, L., Segers, H., Maat, A., Kool, M., Hoving, E.W., van den Heuvel-Eibrink, M.M., Nicholson, J., Straathof, K., Hook, L., de Krijger, R.R., Trayers, C., Allinson, K., Behjati, S.#, Drost, J.#. Somatic mutations and single-cell transcriptomes reveal the root of malignant rhabdoid tumours. Nature Communications 2021 Mar 3; 12(1):1407. doi: 10.1038/s41467-021-21675-6.

  5. Calandrini, C.*, Schutgens, F.*, Oka, R., Margaritis, T., Candelli, T., Mathijsen, L., Ammerlaan, C., van Ineveld, R.L., Derakhshan, S., de Haan, S., Dolman, E., Lijnzaad, P., Custers, L., Begthel, H., Kerstens, H.H.D., Rookmaker, M., Verhaar, M., Tytgat, G.A.M., Kemmeren, P., de Krijger, R.R., Al-Saadi, R., Pritchard-Jones, K., Kool, M., Rios, A., van den Heuvel-Eibrink, M.M., Molenaar, J., van Boxtel, R., Holstege, F.C.P., Clevers, H., Drost, J. An organoid biobank for childhood kidney cancers that captures disease and tissue heterogeneity. Nature Communications 2020;11(1):1310. doi: 10.1038/s41467-020-15155-6.

Members

Jarno Drost
Oncode Investigator
Aleksandra Nenova    
PhD Student
Carla Rios Arceo    
PhD student
Charlotte Op 't Hoog    
Phd student
Giulia Perticari    
PhD student
Jiayou He    
PhD student
Marian Groot Koerkamp    
Research Technician
Mariel Brok    
Research technician
Marjolein Kes    
PhD student
Mark Dings    
PostDoc
Maroussia Ganpat    
PhD Student
Michael Meister    
Clinical Scientist
Nadia Anderson    
Technician
Rugile Januskeviciute    
PhD student
Sofia Doulkeridou    
Research Technician