Jos Jonkers Group

Mouse models of breast cancer

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Our Focus

My group studies human breast cancer development and progression, as well as therapy response and resistance, in genetically engineered murine models (GEMMs) and patient-derived tumour xenograft (PDX) models. We have developed models for BRCA1/2-associated breast cancer, invasive lobular carcinoma (ILC), ductal carcinoma in situ (DCIS) and oestrogen receptor (ER) positive breast cancer. These models are used to (1) study tumour cell-intrinsic and -extrinsic mechanisms of breast cancer development and progression; (2) develop novel therapeutic strategies for prevention and treatment of breast tumours; (3) study mechanisms of acquired resistance to targeted therapeutics. 

About Jos Jonkers

My Research

Jos Jonkers performed his PhD research (on retroviral insertional mutagenesis screens to identify oncogenes involved in lymphoma progression) in the group of Anton Berns at the NKI. In 1996 he became a postdoc in the Berns lab, where he developed GEMMs of BRCA1/2-associated breast cancer. In 2002, he joined the lab of Allan Bradley at the Wellcome Trust Sanger Institute to develop platforms for DNA copy number analysis of mouse tumors. He became a junior group leader at the NKI in 2003; was appointed as permanent staff member in 2008; and became Head of the Division of Molecular Pathology in 2012.

Major breakthroughs were:

  1. development of GEMMs of ILC and BRCA1/2-associated breast cancer

  2. identification of multiple mechanisms of therapy resistance in BRCA1-deficient breast cancer

  3. development of functional assays for classification of BRCA1 variants of unknown clinical significance

  4. development of CRISPR/Cas9-based non-germline GEMMs of breast cancer

Awards
  • 2018: Awarded the Stand Up To Cancer (SU2C) Laura Ziskin Prize In Translational Cancer Research

  • 2017: Awarded Cancer Research UK (CRUK) Grand Challenge grant

  • 2014: NWO VICI grant

  • 2013: ERC Synergy Grant

  • 2012: EMBO membership

  • 2002: NWO Genomics Fellowship

  • 2002: NWO VIDI grant

Key Publications
  1. Annunziato, S., Kas, S. M., Nethe, M., Yücel, H., Del Bravo, J., Pritchard, C., ... & Schut, E. (2016). Modeling invasive lobular breast carcinoma by CRISPR/Cas9-mediated somatic genome editing of the mammary gland. Genes & development, 30(12), 1470-1480.

  2. Bouwman, P., Aly, A., Escandell, J. M., Pieterse, M., Bartkova, J., van der Gulden, H., ... & Haffty, B. G. (2010). 53BP1 loss rescues BRCA1 deficiency and is associated with triple-negative and BRCA-mutated breast cancers. Nature Structural and Molecular Biology, 17(6), 688.

  3. Bouwman, P., van der Gulden, H., van der Heijden, I., Drost, R., Klijn, C. N., Prasetyanti, P., ... & Jonkers, J. (2013). A high-throughput functional complementation assay for classification of BRCA1 missense variants. Cancer discovery, 3(10), 1142-1155.

  4. Drost, R., Bouwman, P., Rottenberg, S., Boon, U., Schut, E., Klarenbeek, S., ... & Pieterse, M. (2011). BRCA1 RING function is essential for tumor suppression but dispensable for therapy resistance. Cancer cell, 20(6), 797-809.

  5. Jaspers, J. E., Kersbergen, A., Boon, U., Sol, W., van Deemter, L., Zander, S. A., ... & Doroshow, J. H. (2013). Loss of 53BP1 causes PARP inhibitor resistance in Brca1-mutated mouse mammary tumors. Cancer discovery, 3(1), 68-81.

  6. Kas, S. M., de Ruiter, J. R., Schipper, K., Annunziato, S., Schut, E., Klarenbeek, S., ... & Adams, D. J. (2017). Insertional mutagenesis identifies drivers of a novel oncogenic pathway in invasive lobular breast carcinoma. Nature genetics49(8), 1219.

Members

Jos Jonkers
Division Head, Division Moleculalr Pathology
Ana Moises da Silva    
PhD student
Anna Khalizieva    
Phd student
Anne Paulien Drenth    
Technician
Catrin Lutz    
PhD
Eline van der Burg    
Technician
Ellen Wientjens    
Technician
Hanneke van der Gulden    
Technician
Ingrid van der Heijden    
Technician
Julia Houthuijzen    
Postdoc fellow
Julia Yemelyanenko Lyalenko    
PhD Student
Julia-Star Darnold    
Onderzoeker in Opleiding
Kaylee Keller    
Postdoc fellow
Konstantina Strepi    
Phd student
Sarah Moser    
PhD student
Sophie Horst    
Msc
Stefan Hutten    
PhD student