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Drost Group

Jarno Drost

Jarno Drost obtained his master’s degree in Biomolecular sciences from the Free University in Amsterdam (cum laude). He obtained his PhD in 2012, which was executed at the Netherlands Cancer Institute in the group of Reuven Agami. His research led to the identification of a novel tumour suppressor gene acting in the P53 pathway and the discovery that P53 binds and regulates enhancer elements through the production of enhancer RNAs. He subsequently joined the lab of Hans Clevers at the Hubrecht Institute for postdoctoral training, focussing on the exploitation of the organoid technology for cancer research. He was involved in the establishment of the organoid culture system for healthy and tumour prostate tissue and developed colorectal cancer progression models in human intestinal organoids using CRISPR/Cas9 technology. He exploited these models to study hallmarks of tumorigenesis, including chromosome instability and metastasis. For this work he received a NWO VENI fellowship. In 2016 he was appointed group leader at the Princess Máxima Center for pediatric oncology, where he will explore pediatric kidney tumors using the organoid technology.

Research

Kidney cancers represent approximately 7% of all cancer diagnoses among children. Although the overall survival rates have significantly increased, certain high risk subgroups still have a very poor prognosis. Our research focusses on studying the molecular mechanisms underlying high-risk pediatric kidney cancers. The organoid technology allows the unlimited in vitro growth of healthy and diseased tissue from individual patients, while retaining the characteristics of the tissue they were derived from. Pediatric kidney cancer-derived organoids will be established and used for genetic characterization, drug discovery and the development of assays predicting treatment outcome. Additionally, we will exploit organoids in combination with genome editing tools to study the signalling pathways underlying high-risk cases. Among others, we will use CRISPR/Cas9-mediated genome editing in human kidney organoids to introduce and study the consequences of specific genetic alterations using state-of-the-art tools including imaging and next generation sequencing techniques.

Key publications

  • Drost, J.*,#, Karthaus, W.R.*, Gao, D., Driehuis, E., Sawyers, C.L., Chen, Y., Clevers, H.# Organoid culture systems for prostate epithelial tissue and prostate cancer tissue. Nature Protocols 2016 Feb, 11 (2) 347 - 358.
  • Drost, J., van Jaarsveld, R.H., Ponsioen, B., Zimberlin, C., van Boxtel, R., Buijs, A., Sachs, N., Overmeer, R.M., Offerhaus, G.J., Begthel, H. Korving, J., van de Wetering, M., Schwank, G. Logtenberg, M., Cuppen, E., Snippert, H.J., Medema, J.P., Kops, G. J. P. L., Clevers, H. Sequential cancer mutations in cultured human intestinal stem cells. Nature 2015 May 7, 521 (7550): 43 – 47.
  • Karthaus, W.R., Iaquinta, P.J., Drost, J., Gracanin, A., van Boxtel, R., Wongvipat, J., Dowling, C.M., Gao, D., Begthel, H., Sachs, N., Vries, R.G., Cuppen, E., Chen, Y., Sawyers, C.L., Clevers, H.C. Identification of multipotent luminal progenitor cells in human prostate organoid cultures. Cell 2014 Sep 25, 159 (1): 163 – 175.
  • Melo, C.A.*, Drost, J.*, Wijchers, P.J., van de Werken, H., de Wit, E., Oude Vrielink, J.A., Elkon, R., Melo, S.A., Leveille, N., Kalluri, R., de Laat, W. and Agami, R. eRNAs are required for p53-dependent enhancer activity and gene transcription. Molecular Cell 2013 Feb 7; 49 (3): 524 – 535.
  • Drost, J.*, Mantovani, F.*, Tocco, F., Elkon, R., Comel, A., Holstege, H., Kerkhoven, R., Jonkers, J., Voorhoeve, P.M., Agami, R. and Del Sal, G. BRD7 is a candidate tumour suppressor gene required for p53 function. Nature Cell Biology 2010 Apr; 12 (4): 380 – 389.

    # Corresponding author
    * Shared authorship

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