Cover Page
The handle http://hdl.handle.net/1887/73551 holds various files of this Leiden University
dissertation.
Author: Ruiter, J.R. de
Title: Into the blue...Using mouse models to uncover genes driving tumorigenesis and
therapy resistance in human breast cancer
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Curriculum vitae
Julian de Ruiter was born on December 14th, 1988 in Farnborough, Great Britain. He spent his first school years at Green Street Green Primary School, before moving back to the Netherlands with his parents in 1999. In 2001, he started secondary school at the Gymnasium Felisenum in Velsen, from which he graduated in 2007. In the same year, he started the Computer Science Bachelor program at the Delft University of Technology (TUD), from which he graduated with distinction in 2009. During the third and final year of this program, he and several others developed an application for visualizing and statistically analyzing aCGH copy number profiles as part of their final bachelor project, which won the UFD Imtech grant, an award that is given to the best five bachelor projects developed by students at the TUD in a given year.
This bachelor project piqued Julian’s interest in the biological sciences, which is why he enrolled in the Bioinformatics track of the TUD Computer Science master program in 2009. During the first year of this master, he also enrolled in an honors track program, allowing him to follow additional computer science courses outside of the standard curriculum. Next to his studies, Julian was chairman of the 21st board of the student sport club DSZ WAVE, which supports and promotes the sports of water polo, swimming and triathlon for students in Delft. In the second year of his master, Julian spent four months in the group of Ilya Shmulevich at the Institute for Systems Biology in Seattle, where he explored the use of multi-scale signal analysis for studying patterns in chromatin modification at different scales along the genome. After this internship, he performed his master thesis work on developing approaches for interpreting Random Forest classifiers and using these to gain insight into complex biological problems. With the completion of his thesis work, Julian graduated from the master program with distinction in 2012.
After obtaining his master’s degree, Julian started as a PhD student in the group of Jos Jonkers at the Netherlands Cancer Institute in November 2012, under the joint supervision of Jos Jonkers and Lodewyk Wessels. During his PhD project, he used insertional mutagenesis strategies and de novo sequencing approaches to identify genes involved in breast cancer development and therapy resistance. The results of this work are described extensively in this thesis. In February 2018, Julian concluded his PhD work and accepted a position as a Machine Learning Engineer at GoDataDriven, where he aims to further expand his skills in developing data intensive applications and applying these to solve complex machine learning problems.
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List of publications
Kuilman, T., Velds, A., Kemper, K., Ranzani, M., Bombardelli, L., Hoogstraat, M., ... de Ruiter, J.R., ... Krijgsman, O. (2015).CopywriteR: DNA copy number detection from off-target sequence data. Genome Biology, 16(1).
Ray Chaudhuri, A., Callen, E., Ding, X., Gogola, E., Duarte, A.A., Lee, J.E., ... de Ruiter, J.R., ... Nussenzweig, A. (2016). Replication fork stability confers chemoresistance in BRCA-deficient cells. Nature, 535(7612), 382–387.
Ter Brugge, P., Kristel, P., Van Der Burg, E., Boon, U., De Maaker, M., Lips, E., ... de Ruiter, J.R., ... Jonkers, J. (2016). Mechanisms of therapy resistance in patient-derived xenograft models of BRCA1-deficient breast cancer. Journal of
the National Cancer Institute, 108(11).
Boelens, M.C., Nethe, M., Klarenbeek, S., de Ruiter, J.R., Schut, E., Bonzanni, N., ... Jonkers, J. (2016). PTEN Loss in E-Cadherin-Deficient Mouse Mammary Epithe-lial Cells Rescues Apoptosis and Results in Development of Classical Invasive Lobular Carcinoma. Cell Reports, 16(8), 2087–2101.
de Ruiter, J.R., Knijnenburg, T., de Ridder, J. (2017).Mining the forest: uncover-ing biological mechanisms by interpretuncover-ing Random Forests. Bioarxiv.
Kas, S.M.*, de Ruiter, J.R.*, Schipper, K.*, Annunziato, S., Schut, E., Klarenbeek,
S., ... Jonkers, J. (2017). Insertional mutagenesis identifies drivers of a novel oncogenic pathway in invasive lobular breast carcinoma. Nature Genetics, 49(8),
1219–1230.
*Contributed equally to this work.
de Ruiter, J.R., Kas, S.M., Schut, E., Adams, D.J., Koudijs, M.J., Wessels, L.F.A., Jonkers, J. (2017). Identifying transposon insertions and their effects from RNA-sequencing data. Nucleic Acids Research, 3(12), 636–647.
Kas, S. M.*, de Ruiter, J. R.*, Schipper, K., Schut, E., Bombardelli, L., Wientjens, E., ... & Smith, P. D. (2018). Transcriptomics and transposon mutagenesis identify multiple mechanisms of resistance to the FGFR inhibitor AZD4547. Cancer
research, 78(19), 5668-5679.
*Contributed equally to this work.
Gogola, E., Duarte, A. A.*, de Ruiter, J. R.*, Wiegant, W. W., Schmid, J. A., de Bruijn,
R., ... & van den Broek, B. (2018). Selective Loss of PARG Restores PARylation and Counteracts PARP Inhibitor-Mediated Synthetic Lethality. Cancer cell, 33(6), 1078-1093.
*Contributed equally to this work
de Ruiter, J. R., Wessels, L. F. A., & Jonkers, J. (2018). Mouse models in the era of large human tumour sequencing studies. Open biology, 8(8), 180080.
Kluin, R. J., Kemper, K., Kuilman, T., de Ruiter, J. R., Iyer, V., Forment, J. V., ... & Klarenbeek, S. (2018). XenofilteR: computational deconvolution of mouse and human reads in tumor xenograft sequence data. BMC bioinformatics, 19(1), 366.
Annunziato, S.*, de Ruiter, J.R.*, Henneman, L.*, Brambillasca, C.S.*, Lutz, C., Vail-lant, F., Ferrante, F., Drenth, A.P., van der Burg, E., Siteur, B., van Gerwen, B., de Bruijn, R., van Miltenburg, M.H., Huijbers, I.J., van de Ven, M., Visvader, J.E., Lin-deman, G.J., Wessels, L.F.A., Jonkers, J. (2019)Comparative oncogenomics and iterative mouse modeling identifies combinations of driver genes and drug tar-gets in BRCA1-mutated breast cancer. Nature Communications, 10, 397.
*Contributed equally to this work.
Kas, S.M., de Ruiter, J.R., Schut, E., Bleijerveld, O.B., Klarenbeek, S., Wientjens, E., van Miltenburg, M.H., Drenth, A.P., van der Burg, E., Boon, U., Wessels, L.F.A., Jonkers, J. In vivo oncogenicity of FGFR2 is modulated by multiple C-terminal domains. Manuscript in preparation.
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Acknowledgements
Over the past years, I have been fortunate to work in a stimulating environment with many wonderful, enthusiastic and dedicated people — without whom this thesis would not have been possible.
Jos, I have yet to meet someone with more passion for science than you. Thank you for your boundless enthusiasm, which made it easy to believe in our work. I enjoyed the many inspiring discussions we’ve had together — both inside and outside the lab — and I hope that we’ll continue to cross paths!
Lodewyk, thank you for the amazing opportunity to work in not one, but two groups with experts in both machine learning and biology. With your keen but critical eye, you and Jos were a perfect duo for pushing our work to a higher level. I hope you keep doing great things together!
Sjors, our complementary skills made us an excellent team and we can definitely be proud of the papers that we wrote together. I think you’re a great scientist and am curious to see what you’ll achieve in the future. We’ll definitely come to visit you in Manchester!
Koen, thank you for all your contributions to the SB paper, which were crucial in pushing the story to the next level. Outside work, I’ve had a lot of fun ski-ing/snowboarding together in the Alps and I hope that we can keep doing these trips in the future!
Stefano and Chiara, you were great office mates and I very much enjoyed work-ing together on the oncogenomics project. Thank you for also stimulatwork-ing our social development by organizing many Italian dinners, go-karting sessions and the memorable ski-trip to Cervinia!
Sander, Nanne and Daniel, you frequently provided me with a listening ear for debating topics of a more computational nature whenever I wanted to escape the biology. Thank you for these discussions and the many beers we enjoyed together after and outside work.
Jeroen and Theo, even though we never quite got round to publishing my master thesis work, I always enjoyed our meetings together. Your critical advice has been of great value to me over the years and I hope we continue to keep in touch.
I would also like to thank the members of myDoctorate Committee for their feed-back on my thesis, as well asPiet, Sven, Jelle and my OIO Committee (Roderick, Bas and Wilbert) for their critical feedback and advice during our meetings and my presentations.
Daarnaast wil ik graag mijn familie en vrienden bedanken voor hun eindeloze interesse in mijn onderzoek en de nodige afleidingen eromheen. Ik ben ook bijzonder dankbaar voor mijn (schoon)ouders, die altijd voor mij klaar stonden en mij de ruimte gaven om mijn dromen na te jagen. En als laatste natuurlijkAnne Paulien, mijn kersverse vrouw! Bedankt voor jouw onvoorwaardelijke steun en oneindige geduld door de jaren heen. Ik ben benieuwd wat de toekomst ons zal brengen en kijk ernaar uit om dat samen te ontdekken.
