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Molecular Pathology: Jos Jonkers

JosJonkers.jpg

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

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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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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Lisette van der Laak-Cornelissen, MSc

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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Eijkman, Timo

Timo Eijkman

Technician

Experience

I completed my bachelor's degree in Biology and medical laboratory research at the University of Applied Sciences in Utrecht. During my internship at the NKI I studied the correlation between viral titers and tumor growth in a somatically engineered mouse model of breast cancer. After my graduation I started as a research technician in the group of Jos Jonkers. Currently I am involved in the creation of rat models of ductal carcinoma in situ (DCIS) for the CRUK Grand Challenge PRECISION project.   

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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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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

Ph.D. 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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Krimpenfort, Paul

Paul Krimpenfort

Academic Staff

Experience

I started as a PhD student in the group of Anton Berns back in the eighties and was involved in setting up the transgenic technology at the NKI.  After my PhD, focused on the use of transgenic mice in T cell development, I spend a short time at Genfarm Europe in Leiden (generating 'Herman', the transgenic bull, for those who remember). I returned to the NKI, again in the Berns lab as a Staff Scientist responsible for the coordination of the NKI Transgenic Facility. In addition I had my own research line apart from the main projects in the Berns lab. As of May 2019 I am a member of the Jonkers lab.

My main interest is the tumor suppressive function of the CDKN2ab locus which encodes the CDK4/6 inhibitors p15INK4b and p16INK4a in addition to p14ARF and is the most frequently affected tumor suppressor locus in a wide range of human cancers next to TP53. Since CDK4 and CDK6 stimulate G1 progression by phosphorylating pRB, the primary effect of p15Ink4b and p16Ink4a inactivation is thought to be the loss of cell cycle control. However, recent observations suggest the implication of Cdk4/6 inhibitor proteins in other tumor cell behavior features e.g. migration and invasiveness.

 

I am also member of the NKI Animal Experimental Committee and the Employee Council (OR).

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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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Moser, Sarah

Sarah Moser

Ph.D. Student

Experience

I obtained my Bachelor's degree in Vienna, Austria and performed my Master studies at the Erasmus Medical Center in Rotterdam. As part of my training I did internships at the Research Center for Molecular Medicine (CeMM) in Vienna focussing on DNA repair disorders, at the Erasmus MC working on the immune system and antigen presentation and at the Netherlands Cancer Institute investigating the regulation of DNA repair pathways.

In October 2018 I joined the group of Jos Jonkers as a PhD student where I aim to discover and characterize novel synthetic lethalities in the DNA damage response.

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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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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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Yemelyanenko Lyalenko, Julia

Julia Yemelyanenko Lyalenko

Technician

Experience

I completed my Bachelor's degree in Human Biology at the Pompeu Fabra University in Barcelona, Spain, during which I did two research internships abroad, one in Hungary and another in Australia. Then, I obtained my Master's degree in Oncology at the Vrije Universiteit Amsterdam. During my Master's, I did two more internships, one at the VUmc Cancer Center Amsterdam and another in the research group of Jos Jonkers at the NKI. In January 2019 I joined the Jonkers group as a technician, mainly focusing on validating a novel potential mTOR inhibitor resistance mechanism in invasive lobular carcinoma.

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Zimmerli, Dario

Dario Zimmerli

Postdoctoral Fellow

Experience

I obtained my Master in developmental biology from the University of Zürich in 2011. During my PhD in the lab of Konrad Basler (2013-2017), I studied nuclear Wnt-signaling components in embryonic development and the role of Wnt-signaling in squamous cell carcinomas. I stayed for a Postdoc to generate mouse models via CRISPR/Cas9 and applied the knowledge gained from the embryonic studies in cancer organoids.

In 2019, I joined the lab of Jos Jonkers as Postdoc to study the role of the innate immune system in mammary carcinoma initiation, progression and metastasis and the feasibility of targeting these pathways for treatment.

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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 S, Krastev DB, Song F, Brandsma I, Frankum J, Brough R, Sherker A, Landry S, Szilard RK, Munro MM, McEwan A, Goullet de Rugy T, Lin ZY, Hart T, Moffat J, Gingras AC, Martin A, van Attikum H, Jonkers J, Lord CJ, Rottenberg S, Durocher D.

    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 B, Barazas M, Kersbergen A, van de Ven M, Tarsounas M, Ogilvie DJ, van Vugt M, Wessels LFA, Bartkova J, Gromova I, Andújar-Sánchez M, Bartek J, Lopes M, van Attikum H, Borst P, Jonkers J, Rottenberg S.

    Link to PubMed
 
 

Recent publications View All Publications

  • Rebalancing of actomyosin contractility enables mammary tumor formation upon loss of E-cadherin

    (2019) Nat Commun. Aug 23;10(1):3800. doi: 10.1038/s41467-019-11716-6.

    Schipper K, Seinstra D, Paulien Drenth A, van der Burg E, Ramovs V, Sonnenberg A, van Rheenen J, Nethe M, Jonkers J.

    Link to PubMed
  • Loss of p53 triggers WNT-dependent systemic inflammation to drive breast cancer metastasis

    (2019) Nature. Aug;572(7770):538-542. doi: 10.1038/s41586-019-1450-6. Epub 2019 Jul 31.

    Wellenstein MD, Coffelt SB, Duits DEM, van Miltenburg MH, Slagter M, de Rink I, Henneman L, Kas SM, Prekovic S, Hau CS, Vrijland K, Drenth AP, de Korte-Grimmerink R, Schut E, van der Heijden I, Zwart W, Wessels LFA, Schumacher TN, Jonkers J, de Visser KE.

    Link to PubMed
 

Contact

  • Office manager

    Suzanne Romijn

  • E-mail

    s.romijn@nki.nl

  • Telephone Number

    +31 20 512 9168

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