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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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Mirjam Boelens, Ph.D.

Postdoctoral fellow

Experience

I graduated from University Medical Center Groningen in 2008 at molecular genetics of lung cancer and COPD. Using my earned KWF fellowship, I then joined the group of Andy J. Minn, at University of Chicago and University of Pennsylvania where I studied the role of fibroblasts in radiotherapy response of breast cancer. Currently, I am working in the group of Jos Jonkers on the role of fibroblasts in invasive lobular carcinoma using genetically engineered mouse models.

 

 

 

 

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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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Petra ter Brugge, Ph.D.

Postdoctoral fellow

Experience

After finishing my PhD in Nijmegen, I did a postdoc in Rotterdam (department of Immunology) where I developed a mouse model for chronic lymphocytic leukemia (CLL). I started working at the NKI in 2008, on a project to produce patient-derived xenograft (PDX) models for breast cancer. I am now using these PDX models to study the sensitivity of BRCA1-deficient triple-negative breast tumors to different treatments and to identify biomarkers to predict therapy response. I also study the development of therapy resistance in PDX models and try to unravel the underlying resistance mechanisms.

 

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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 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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Grimmerink, Renske

Renske de Korte-Grimmerink

Technician

Experience

In June 2014, I completed my Bachelor degree in Life Sciences at the Hogeschool Utrecht. My specialization is Zoology. My first internship was at the AMC. There I worked on a project that looked at the effect of  chronic administration of the late sodium current blocker ranolazine in SCN5A-1798insD mice.
My second  internship was at the NKI. During this internship I looked at the response of BRCA1 deficient breast tumors to Cisplatin and Olaparib. From July 2014, I work as a technician in the group of Jos Jonkers. I work mostly together with Anne-Paulien Drenth.

 

 

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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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Linda Henneman, Ph.D.

Postdoctoral fellow

Experience

I finished my Master in Biomedical Science at the VU University Amsterdam in 2004. In the same year I started as a PhD student in the group of Ron Wanders at the Academic Medical Centre in Amsterdam. I received my PhD in 2011. In 2009, I started as a postdoc in the groups of Ed Roos and Kees Jalink at the NKI. In 2011, I started my second postdoc in the group of Jos Jonkers, where I am developing genetically engineered mouse models (GEMMs) to study ER-positive breast cancer. I am also using GEMMs to validate several candidate oncogenes in BRCA1-associated breast cancer.

 

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Sjors Kas, MSc

Ph.D. Student

Personal details

Experience

I performed my Master Oncology training at the Free University Medical Center, Amsterdam during 2009-2011. My first internship was at the Cancer Center Amsterdam in 2010 in the group of Prof. dr. G.J. Peters. My second internship was at the Netherlands Cancer Institute, Amsterdam in the group of Jos Jonkers, where I, after obtaining my Master degree, started as a PhD-student in September 2011. At the moment I am working on the identification of novel cancer genes involved in the development of invasive lobular breast carcinoma. Additionally I am studying possible treatment options for this breast cancer subtype.

 

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Martine van Miltenburg, Ph.D.

Postdoctoral fellow

Experience

I obtained my Master in Biomedical Sciences (VU Amsterdam), after which I explored Thailand, Laos and Vietnam by bicycle. I received my PhD training (2004-2010) in the lab of Prof. van de Water at Leiden University where I studied the role of FAK in regulating contractility in mammary gland development and lactation. In addition, I identified AnxA1 as an important player in breast cancer progression. Currently, I am using genetically engineered mouse models to study the tumorigenic potential of PIK3CA mutants in invasive lobular breast cancer. In addition, I am studying the role of epithelial-to-mesenchymal (EMT) transition in resistance of BRCA1-deficient triple-negative breast cancer to PARP inhibitors.

 

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Micha Nethe, Ph.D.

Postdoctoral fellow

Experience

I obtained my PhD degree in January 2011 in the group of Peter Hordijk at Sanquin. During this PhD training I studied the role of the RhoGTPase Rac1 in cell motility and cellular junction integrity. After obtaining my PhD degree, I joined the group of Ian Macara as a post-doctoral fellow at the University of Virginia. I developed a peptide-based strategy to analyze the importance of the orientation of the mitotic spindle during mammary gland development, for which I obtained the NWO Rubicon grant. Starting October 2013 I joined the group of Jos Jonkers to continue this research. I will use this peptide-based strategy to develop transgenic mouse models to study the contribution of spindle mis-orientation to breast cancer development.

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Puppe, Julian

Julian Puppe, MD

Postdoctoral fellow

Experience

After finishing my medical studies in Dresden, Germany and Harvard Medical School, USA I started my residency program in 2011 at the University Hospital of Cologne in the Department of Gynecology & Obstetrics. During my MD-program I joined the group of Maarten van Lohuizen at the NKI in 2008 where we were looking into the role of the Polycomb Protein EZH2 in BRCA1-deficient breast cancer cells. I am now back at the NKI to continue my work on EZH2 in the laboratory of Jos Jonkers in collaboration with Maarten van Lohuizen and Rita Schmutzler (German Consortium for Hereditary Breast- and Ovarian Cancer, Cologne) by using mouse models for hereditary breast cancer to evaluate potential epigenetic treatments.

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Julian de Ruiter

Ph.D. Student

Experience

I obtained my bachelor degree in Computer Sciences (with a minor in Life Sciences) at the Delft University of Technology in 2010. In 2012 I completed my masters degree in Bioinformatics at the same university, with my masters dissertation focusing on creating interpretable models from Random Forest classifiers applied to biological datasets.

At the Netherlands Cancer Institute. I am currently working on the application and development of novel algorithms for analysis of NGS data to identify mechanisms of resistance against targeted therapies in triple negative breast cancer and invasive lobular carcinomas.

 

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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

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.

 

 

 

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Feijtel, Danny

Danny Feijtel

Student technician

Personal details

Experience

My name is Danny Feijtel and I'm a biomedical laboratory science student (HLO) at Avans, Breda. Right now I am in my final year. I am working, as an intern, in the group of Jos Jonkers and my project focusses on the mechanism(s) involving tyrosine receptor kinase MET and epithelial-to-mesenchymal transition in triple negative breast cancer therapy resistance. Also I'm working to obtain my article 12 certificate.

 

 

 

 

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Anja Maag

Master Student

Personal details

Experience

I am a Master student performing my second internship at the Netherlands Cancer Institute. Last year, I achieved the Bachelor's degree in Chemistry at the university of Amsterdam and started a Master in Biomolecular Science at the VU Amsterdam. I performed my previous internship at the NKI in the group of Titia Sixma. During this internship,  I am going to work on the functions of BRCA1 and 2 and their response to targeted therapy.

 

 

 

 

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Key publications View All Publications

  • BRCA1 RING function is essential for tumor suppression but dispensable for therapy resistance

    (2011) Cancer Cell. 20: 797-809

    Drost R, Bouwman P, Rottenberg S, Boon U, Schut E, Klarenbeek S, Klijn C, van der Heijden I, van der Gulden H, Wientjens E, Pieterse M, et al.

    Link to PubMed
  • 53BP1 loss rescues BRCA1 deficiency and is associated with triple-negative and BRCA-mutated breast cancers

    (2010) Nat Struct Mol Biol. 17: 688-695.

    Bouwman P, Aly A, Escandell JM, Pieterse M, Bartkova J, van der Gulden H, Hiddingh S, Thanasoula M, Kulkarni A, Yang Q, Haffty BG, Tommiska et al.

    Link to PubMed
 
 

Recent publications View All Publications

  • Rapid target gene validation in complex cancer mouse models using re-derived embryonic stem cells

    EMBO Mol Med. 2014 Jan 8. [Epub ahead of print]

    Huijbers IJ, Bin Ali R, Pritchard C, Cozijnsen M, Kwon MC, Proost N, Song JY, de Vries H, Badhai J, Sutherland K, Krimpenfort P, Michalak...

    Link to PubMed
  • A high-throughput functional complementation assay for classification of BRCA1 missense variants

    Cancer Discov. 2013 Oct;3(10):1142-55. doi: 10.1158/2159-8290.CD-13-0094. Epub 2013 Jul 18.

    Bouwman P, van der Gulden H, van der Heijden I, Drost R, Klijn CN, Prasetyanti P, Pieterse M, Wientjens E, Seibler J, Hogervorst FB,...

    Link to PubMed
 

Contact

  • Office manager

    Mirna Ekelschot - van Diermen

  • E-mail

    m.v.diermen@nki.nl

  • Telephone Number

    +31 20 512 9127

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