Molecular Pathology: Jos Jonkers
Jos Jonkers, Ph.D. professorHead of the Division, Groupleader
- +31 20 512 2000
- 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).
- Stefano AnnunziatoPh.D. Student
- Mirjam Boelens, Ph.D.Postdoctoral fellow
- Peter Bouwman, Ph.D.Postdoctoral fellow
- Chiara BrambillascaPh.D. Student
- Petra ter Brugge, Ph.D.Postdoctoral fellow
- Eline van der Burg, BAScTechnician
- Lisette Cornelissen, MScPh.D. Student
- Dr. Martina DettwilerGuest
- Anne Paulien Drenth, MScTechnican
- Hanneke van der GuldenTechnician
- Ingrid van der Heijden, Ing.Technician
- Linda Henneman, Ph.D.Postdoctoral fellow
- Sjors Kas, MScPh.D. Student
- Anja MaagTechnician
- Martine van Miltenburg, Ph.D.Postdoctoral fellow
- Arne Nedergaard KousholtPostdoctoral fellow
- Micha Nethe, Ph.D.Postdoctoral fellow
- Dr. Frank RolfsPostdoctoral fellow
- Julian de RuiterPh.D. Student
- Koen Schipper, MscPh.D. Student
- Eva Schut, BASc Technician
- Marieke van de Ven, Ph.D.Postdoctoral fellow
- Ellen WientjensTechnician / Lab Manager
- Hatice YücelMaster Student
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.
Mirjam Boelens, Ph.D.
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.
Peter Bouwman, Ph.D.
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.
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
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.
Petra ter Brugge, Ph.D.
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.
Eline van der Burg, BASc
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.
Lisette Cornelissen, MSc
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.
Dr. Martina Dettwiler
I am DVM with a specialization in animal pathology. Since 2014 I am working in the group of Prof. Sven Rottenberg in the Institute of Animal Pathology, University of Bern, on my PhD project investigating the role of LRRC8 proteins on platinum drug resistance in Brca-deficient mammary tumors. I am staying at the NKI for one year to get experienced in loss-of-function screens using the CRISPR/Cas9 technique. Goal of my project here is to find new mechanisms of platinum resistance in the Brca-deficient mammary tumor cells. My internship is supported by a Swiss National Foundation Doc.Mobility grant.
Anne Paulien Drenth, MSc
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.
Hanneke van der Gulden
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.
Ingrid van der Heijden, Ing.
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.
Linda Henneman, Ph.D.
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.
Sjors Kas, MSc
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.
I completed the Master Biomolecular Sciences at the VU university. During this study I performed my first internship at the NKI in the group of Titia Sixma and there I studied the role of BRCA1 during histone H2A ubiquitination. The second internship I performed at the NKI in the lab of Jos Jonkers and I studied the histone H2A ubiquitination by BRCA1 in DNA damage repair. After completing the Master, I started as technician in the group Jos Jonkers and there, I will continue my work on the functions of BRCA1 and its response to targeted therapy.
Martine van Miltenburg, Ph.D.
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.
Arne Nedergaard Kousholt
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).
Micha Nethe, Ph.D.
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.
Dr. Frank Rolfs
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.
Julian de Ruiter
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.
Koen Schipper, Msc
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.
Eva Schut, BASc
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.
Marieke van de Ven, Ph.D.
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.
Technician / Lab Manager
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.
I completed my bachelor's degree in Biomedical Research at the Hogeschool Rotterdam (2009 - 2014) and am currently doing the master Oncology at the Free University in Amsterdam. During my bachelor program I did my minor internship in the group of Piet Borst at the NKI (Feb 2012 - August 2012) and my major internship in the group of Robert G Bristow at the Princess Margaret Cancer Centre in Toronto (May 2013 - May 2014). Currently I started my minor internship in the group of Jos Jonkers where I will be working on genetic screens using the CRISPR-Cas9 system.
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 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
BRCA1 and CtIP promote alternative non-homologous end-joining at uncapped telomeres
(2015) EMBO J. 2015 Feb 3
Badie S, Carlos AR, Folio C, Okamoto K, Bouwman P, Jonkers J, Tarsounas M.Link to PubMed
Prolonged Ezh2 Depletion in Glioblastoma Causes a Robust Switch in Cell Fate Resulting in Tumor Progression
(2015) Cell Rep. 2015 Jan 14
de Vries NA, Hulsman D, Akhtar W, de Jong J, Miles DC, Blom M, van Tellingen O, Jonkers J, van Lohuizen M.Link to PubMed
Mirna Ekelschot - van Diermen
+31 20 512 9127
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