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Molecular Pathology: Jos Jonkers

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Jos Jonkers, Ph.D. professorHead of the Division, Groupleader

About Jos Jonkers

Research interest: Mouse Models of Breast Cancer

The focus of our group is on the genetic dissection of human breast cancer through the use of advanced mouse models. For this, we have developed genetically engineered mouse models (GEMMs) for p53-induced breast cancer, BRCA1- and BRCA2- associated hereditary breast cancer, and E-cadherin-mutated lobular breast cancer. We have also developed a panel of patient-derived xenograft (PDX) models of BRCA1-proficient and BRCA1-deficient triple-negative breast cancer.

We are using these mouse models to (1) investigate genotype-phenotype relations in mammary tumorigenesis; (2) identify genetic changes underlying breast tumorigenesis; (3) study the role of stromal fibroblasts in mammary tumorigenesis; (4) develop prophylactic therapies for prevention of breast tumors in BRCA1-mutation carriers; (5) develop combination therapies targeting BRCA-deficient mammary tumors; (6) study mechanisms of acquired resistance to targeted therapeutics such as PARP inhibitors, FGFR inhibitors and PI3K inhibitors.

For these studies we combine in vivo mouse models and in vitro systems (tumor cell lines and primary mammary epithelial cells) with genomics approaches (gene expression profiling, next-generation sequencing, proteomics) and functional genomics screens (RNAi, transposon tagging).

 

Links

Protocols

Co-workers

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Stefano Annunziato

Ph.D. Student

Experience

I achieved my Master degree in Medical Biotechnology in Milan, Italy, working in Dr. Eugenio Montini's lab at the San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), directed by Prof. Luigi Naldini. My experimental thesis title was "Identification of genes involved in the resistance to targeted anti-cancer therapies by lentiviral vector-based insertional mutagenesis". After that, I started my PhD in Jos Jonkers' lab, where I am performing in vitro and in vivo forward genetics screens to identify drug resistance genes in different breast cancer models.

 

 

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Badoux, Madelon

Madelon Badoux

Technician

Experience

I completed my Bachelor in Biology and Medical Laboratory Research at the Hogeschool Leiden University of Applied Sciences. During my internship at the Jos Jonkers group, I produced high-titer lentiviral vectors and monitor tumor growth in breast cancer models. After my internship, I started as a research technician. At the moment I participate in developing in vivo models for Ductal Carcinoma in Situ (DCIS).  

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Bhin, Jinhyuk

Jinhyuk Bhin

Postdoctoral fellow

Experience

I completed my Ph.D program in Pohang University of Science and Technology (POSTECH), South Korea, under the supervision of Prof. Dr. Daehee Hwang. During the Ph.D program, I applied systems biology approaches to decipher underlying molecular bases in complex biological systems including embryonic stem cells and gastric cancer. In January 2017, I joined the labs of Lodewyk Wessels and Jos Jonkers at the NKI.

I am investigating drug resistance of triple negative breast cancer and invasive lobular carcinoma using multi-omics datasets (exome-, cnv-, RNA-sequencing, and mass-spectrometry-based proteomic data).

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Peter Bouwman, Ph.D.

Postdoctoral fellow

Experience

I started my research career as a biochemistry student under supervision of Cor Calkhoven in the laboratory of Geert Ab at the University of Groningen. I performed my PhD research in the laboratory of Sjaak Philipsen and Frank Grosveld at the Erasmus University Rotterdam, where I studied the in vivo functions of the transcription factors SP3 and SP4. After a period in the laboratory of Christine Mummery at the Hubrecht Institute in Utrecht, I continued my work on mouse models for human disease in the laboratory of Jos Jonkers at the Netherlands Cancer Institute, where I focus on the BRCA1 and BRCA2 tumor suppressor genes.

 

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Brambillasca, Chiara

Chiara Brambillasca

Ph.D. Student

Experience

I achieved my Bachelor's and Master's degree in Medical and Pharmaceutical Biotechnologies in Milan, Italy. During my final internship period, I had the chance to work in Dr. Matteo Bellone's group, at the San Raffaele Scientific Park (Milan), where I completed my thesis concerning  the characterization of the immunoregulatory activity of prostate cancer stem cells. Hereafter, I pursued this project as a research fellow in the same laboratory.
In July 2014, I started my PhD joining Jos Jonkers' laboratory, working on genetically engineered mouse models (GEMMs). My aim is to study several cancer genes associated with BRCA1-mutated triple- negative breast cancer.

 

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De Bruijn, Roebi

Roebi de Bruijn

Bioinformatician

Personal details

Groups

Experience

I completed the bachelor Biomedical Sciences at the UvA and subsequently finished the master Life Sciences track Bioinformatics at the UvA/VU. I did my internships at AMC, NKI (Computational Cancer Biology - Wessels) and CWI (Life Sciences - Klau). During these internships I analyzed breast cancer RNA-Seq data by using bioinformatics tools, programming (R/Python/websites) and machine learning.

At the NKI I am currently working in the groups of Jos Jonkers and Lodewyk Wessels on the topic of tumor evolution and therapy resistance in triple negative breast cancer.

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Eline van der Burg, BASc

Technician

Experience

In 2005, I graduated from a Bachelor program of Applied Sciences at the Hogeschool Utrecht. As part of the Bachelor program, I completed two internships at the NKI and Maastricht University. In 2006, I returned to the NKI to join the research group of Jos Jonkers, where I currently work as a research technician on various projects in collaboration with two Postdocs.

 

 

 

 

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Afdeling

Ph.D. Student

Experience

I completed my Master in Biomedical Sciences at the University of Leiden in 2012. During my first internship in the lab of Marie-Jose Goumans (LUMC, Leiden), I studied the role of TGFβ signaling in cardiomyocyte progenitor cells. During my second internship in the lab of Karin de Visser (NKI, Amsterdam), I studied the role of c-Met in breast cancer development and metastasis. After completing my Master I started as a PhD student in the lab of Jos Jonkers (NKI, Amsterdam). I am using in vivo transposon mutagenesis screens to identify genes that collaborate with E-cadherin loss in lobular breast cancer development.

 

 

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Anne Paulien Drenth, MSc

Technican

Experience

I completed my bachelor's degree in Biology and Medical Laboratory Research at the Hogeschool Leiden University of Applied Sciences (HLO) in July 2010. As part of the bachelor program, I did an internship on lipid metabolism in the group of Hans Princen at TNO Leiden (Sept 2009 - June 2010). In March 2013, I obtained my Master of Science degree in Biology and Education at the University of Leiden. In August 2013, I started to work as a technician in the research group of Jos Jonkers at the NKI-AVL. My work focuses on preclinical evaluation of combination therapies for personalized breast cancer treatment and on the identification of resistance mechanisms.

 

 

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Paes Dias, Mariana

Mariana Paes Dias

Ph.D. Student

Experience

I graduated  in Cell and Molecular Biology (NOVA University of Lisbon, Portugal). Next, I obtained my Master's degree in Molecular Medicine and Oncology (University of  Porto, Portugal).

My PhD project aims to identify genes that confer resistance to synthetic lethality drugs in BRCA1/2-deficient tumour cells and to unveil molecular mechanisms leading to drug resistance. I will use cancer cell lines and organoids from genetically engineered mouse models of BRCA1- and BRCA2-deficient breast to conduct in vitro drug resistance screens with genome-wide and DNA damage response focused shRNA and CRISPR/Cas9 libraries.

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Gandaglia, Anna

Anna Gandaglia

Technician

Experience

In 2012, I achieved my Master's degree in Medical Molecular and Cellular Biotechnology at the San Raffaele University in Milan, Italy. During my final internship year, I worked under the mentorship of Prof. Nicoletta Landsberger in the San Raffaele Rett Research Unit, where I stayed for 5 more years, obtaining my PhD in 2015 (PhD Program in Neurobiology, University of Insubria). My period in Prof. Landsberger's lab was dedicated to the study of MeCP2 and the pathogenic mechanisms of Rett Syndrome.

In January 2018 I've started working in Jos Jonkers' group as project manager and organizer of scientific meetings.

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Hanneke van der Gulden

Technician

Experience

I started working as a research technician in the group of Anton Berns at the NKI in 1987. In the Berns lab, I generated several conditional tumor suppressor gene knockout mice. I became lab manager in the group of Jos Jonkers when he started his own lab in 2002. In the Jonkers group, I have been working on several BRCA1-related projects. Together with Peter Bouwman and Ingrid van der Heijden, I developed an ES cell assay system for functional analysis of BRCA1 variants of unknown clinical significance. I also generated mouse mutants mimicking defined human BRCA1 founder mutations (185delAG and 5382insC). I still like DNA cloning most, but I also learned several other techniques during my time at the NKI.

 

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Van der Heijden, Ingrid

Ingrid van der Heijden, Ing.

Technician

Experience

I completed my education in Biochemistry at the Hogeschool Nijmegen in 1996 and started as a technician in the group of Prof. Dr. Gerard Martens at the department of Molecular Animal Physiology (UMC St. Radboud)
In 1998 I moved to the group of Be Wieringa at the department of Celbiology (UMS St Radboud) to work on signaling of protein tyrosine phosphatases. After that I moved to the NKI in 2000 to work on multidrug transporters at the department of Molecular Biology in the group of Prof.dr.Piet Borst (NKI).
Since 2006 I am working at the department of Molecular Pathology (NKI) in the group of Jos Jonkers on various breast cancer related projects.

 

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Julia Houthuijzen, Ph.D.

Postdoctoral fellow

Experience

In 2010 I obtained my Master's degree in Biomedical Science at the University of Utrecht. A few months later I started my PhD training in the group of Prof. Emile Voest at the University Medical Center in Utrecht. During my PhD I discovered a lipid signaling cascade involving splenic macrophages that induces resistance against DNA-damaging chemotherapeutics. In 2016 I started my post doc in the lab of Prof. Jos Jonkers where I am working on the identification and validation of molecular drivers of invasive lobular breast cancer and triple-negative breast cancer using various genetic mouse models.

 

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Hutten, Stefan

Stefan Hutten

Ph.D. Student

Experience

I obtained my BSc and MSc in Molecular Life Sciences at Wageningen University, with a biomedical specialization. During my internship at Massachussets General Hospital/ Harvard Medical School (Boston) I came in contact with cancer research, where I studied the possibility of delivering therapeutic agents by genetically engineered stem cells for Glioblastoma Multiforme.

In June 2017 I started my PhD, which involves characterizing genetic and environmental markers identifying the progression of Ductal Carcinoma in Situ (DCIS). To achieve this I will setup In Vivo models to study the effect of multiple genetic factors on DCIS to Invasive Breast Cancer (IBC) progression.

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Lutz, Catrin

Catrin Lutz

Master Student

Experience

I am a Master student in Oncology at the VU Amsterdam. In my last internship I had the chance to work at the Cancer Center Amsterdam in the Exosomes Research Group, led by Dr. Michiel Pegtel. There I was able to run a pilot study on exosomal urinary biomarkers for the detection of kidney cancer and could aid in researching the functionality of miRNAs in extracellular vesicles. I have now joined the group of Jos Jonkers, where I will assist Stefano in setting up in vitro and in vivo forward genetic screens to identify drug resistance genes in breast cancer models.

 

 

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Moises da Silva, Ana

Ana Moises da Silva

Ph.D. Student

Experience

I obtained my Bachelor's degree in Biology at UFRGS in Brazil where I collaborated as a research trainee at Dr. Lavinia Faccini's group. During my internship, I had the opportunity to work in Dr. Maria Blasco's group at CNIO in Spain.

I achieved my Master degree in Molecular Biomedicine at UAM in Spain and did my final Master dissertation under supervision of Dr. Blasco.

In December 2017 I joined Jos Jonkers' group as a PhD student. The aim of my project is to test novel synthetic lethal interactions in BRCA1-deficient breast cancer mouse models. In addition, I will work on the in vivo validation of known and novel breast cancer susceptibility genes using CRISPR/Cas9-based somatic modeling in mice.

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Nedergaard, Andre

Arne Nedergaard Kousholt

Postdoctoral fellow

Experience

I work as a postdoc in the lab of Jos Jonkers, where I am using advanced mouse models to investigate a potential novel tumour suppressor for breast cancer. I will test if specific genetic changes can cause breast cancer, and using these models, I will study treatment response and drug resistance for these specific breast cancer subtypes. Moreover, I will setup an in-vitro assay for testing pathogenic roles of patient derived breast cancer mutations. I did my PhD under the supervision of associated professor Claus Storgaard Sørensen, BRIC, university of Copenhagen. My primary research experience lies within basic research in the field of the DNA Damage Response (DDR).

 

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Pulver, Emilia

Emilia Pulver

Ph.D. Student

Experience

I received my B.S in Biological Sciences from Cornell University. Afterwards I worked in the Integrative Neurobiology Laboratory at McLean Hospital conducting pre-clinical behavioral drug addiction studies. I joined Sangeeta Bhatia's nanotechnology laboratory at MIT's Koch Institute for Integrative Cancer Research. There, I investigated targeted therapeutics and nanoparticle delivery into pancreatic tumors, as well as synthetic urinary biomarkers and PET/CT imaging for early detection of tumor metastasis.

As a PhD student in the Jonkers lab, I will use non-germline CRISP-Cas9 approaches to test triple negative breast cancer susceptibility genes and engineer BRCA1 conditional detectable alleles and mouse models.

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Dr. Frank Rolfs

Postdoctoral fellow

Experience

I studied biology in Berlin and moved to ETH Zurich afterwards to perform my PhD work in the laboratory of Sabine Werner. There, I explored the role of antioxidant defense in skin carcinogenesis. In a collaborative project with the Laboratory of Connie Jimenez and the group of Jos Jonkers, I will now work on biomarker discovery in patient-derived xenograft models of breast cancer.

 

 

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Koen Schipper, Msc

Ph.D. Student

Experience

I obtained my bachelor and master degree in Bio-Pharmaceutical science at Leiden University. During my master studies I did an internship at the lab of Professor Bob van de Water at the LACDR and my second internship at the lab of Dr. Andrew Ewald at Johns Hopkins university in Baltimore, United States. Since June 2014 I am a PhD student in the lab of Jos Jonkers at the NKI. Here I am working on validation and characterization of novel cancer genes involved in lobular breast carcinoma.

 

 

 

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Eva Schut, BASc

Technician

Experience

I performed my Molecular Biology bachelor training at the Hogeschool Utrecht from 2002 to 2006. My first internship was at Solvay Pharmaceuticals, and my second internship was at the Netherlands Cancer Institute, in the group of Jos Jonkers. After my graduation I directly started as a research technician and got my article 12 certificate in 2008. I have worked on many different projects, together with PhD students and postdocs. I enjoy my work very much, in particular because I am given a high degree of independence, which works very motivating for me.

 

 

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Marieke van de Ven, Ph.D.

Postdoctoral fellow

Experience

I performed my Master in Biomedical Sciences (VU University, Amsterdam) in 2002 and received my Master of Education title in 2003. After obtaining my Master degree, I was a first grade biology teacher for one year. In May 2004, I started my PhD research on nucleotide excision repair in cancer, ageing and stress resistance in the group of Jan Hoeijmakers. I received my Doctors title in May 2009. Since June 2009, I am working as a Postdoc in the group of Jos Jonkers at the Netherlands Cancer Institute. My main focus is on the development of novel (prophylactic) therapies for prevention and treatment of BRCA1-associated breast cancer.

 

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Ellen Wientjens

Technician / Lab Manager

Experience

I am working as a research technician in the Netherlands Cancer Institute since 1988. I have worked in the groups of Anton Berns, Rob Michalides and Maarten van Lohuizen. Since 2006, I am working in the group of Jos Jonkers. I have been involved in several research projects. At the moment I am working together with Mirjam Boelens on the role of fibroblasts in invasive lobular carcinoma using genetically engineered mouse models. In 2015 I also started as a lab manager of the division of Molecular Pathology where I am involved in the organization of this division.

 

 

 

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Zingg, Daniel

Daniel Zingg

Postdoc

Experience

In 2009, I achieved my Master's degree in Cell Biology at the Swiss Federal Institute of Technology (ETH) Zurich, Switzerland. In the course of my PhD in the lab of Lukas Sommer at the University of Zurich, Switzerland (2010-2015), I investigated the relevance of the epigenetic modifier EZH2 for cutaneous melanoma initiation and metastatic progression. Consequently, I became interested in the role of the primary cilium during melanoma initiation, which I pursued investigating as postdoctoral fellow in the Sommer lab.

In 2018, I joined the lab of Jos Jonkers as postdoctoral fellow to study molecular mechanisms contributing to the initiation of invasive lobular breast cancer using genome-wide forward genetic screening in murine mammary epithelial cells and genetically engineered mouse models.

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Key publications View All Publications

  • The shieldin complex mediates 53BP1-dependent DNA repair

    (2018) Nature. Aug;560(7716):117-121. doi: 10.1038/s41586-018-0340-7. Epub 2018 Jul 18.

    Noordermeer SM, Adam S, Setiaputra D, Barazas M, Pettitt SJ, Ling AK, Olivieri M, Álvarez-Quilón A, Moatti N, Zimmermann M, Annunziato et al.

    Link to PubMed
  • Selective Loss of PARG Restores PARylation and Counteracts PARP Inhibitor-Mediated Synthetic Lethality

    (2018) Cancer Cell. Jun 11;33(6):1078-1093.e12. doi: 10.1016/j.ccell.2018.05.008

    Gogola E, Duarte AA, de Ruiter JR, Wiegant WW, Schmid JA, de Bruijn R, James DI, Guerrero Llobet S, Vis DJ, Annunziato S, van den Broek et al.

    Link to PubMed
 
 

Recent publications View All Publications

  • Transcriptomics and Transposon Mutagenesis Identify Multiple Mechanisms of Resistance to the FGFR Inhibitor AZD4547

    (2018) Cancer Res. Aug 16. doi: 10.1158/0008-5472.CAN-18-0757.

    Kas SM, de Ruiter JR, Schipper K, Schut E, Bombardelli L, Wientjens E, Drenth AP, de Korte-Grimmerink R, Mahakena S, Phillips C, Smith...

    Link to PubMed
  • The Tandem Duplicator Phenotype Is a Prevalent Genome-Wide Cancer Configuration Driven by Distinct Gene Mutations

    (2018) Cancer Cell. Aug 13;34(2):197-210.e5. doi: 10.1016/j.ccell.2018.06.008. Epub 2018 Jul 12.

    Menghi F, Barthel FP, Yadav V, Tang M, Ji B, Tang Z, Carter GW, Ruan Y, Scully R, Verhaak RGW, Jonkers J, Liu ET.

    Link to PubMed
 

Contact

  • Office manager

    Suzanne Romijn

  • E-mail

    s.romijn@nki.nl

  • Telephone Number

    +31 20 512 9168

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