This website uses cookies

This websites contains videos from YouTube. This company uses cookies (third party cookies). If you do not want them to use these cookies, you can indicate so here. However, this does mean that you will not be able to watch videos on this website. We also make use of our own cookies in order to improve our website. We don’t share our data with other parties. Read more about our cookie policy

This website uses cookies to enable video and to improve the user experience. If you do not want to accept these cookies, indicate so here. Read more about our cookie policy

Ga direct naar de inhoud, het hoofdmenu, het servicemenu of het zoekveld.

Molecular Genetics: Anton Berns

AntonBerns.jpg

Anton Berns, Ph.D ProfessorSr.Group Leader

About Anton Berns

Research interest

Mouse Cancer Models
The aim is to utilize genetically engineered mouse models to define the (epi)genetic lesions involved in tumor initiation, progression, metastasis and tumor maintenance. These models are particularly suited to design and evaluate new intervention strategies.

Inducible mouse models
We have made a significant investment in developing new mouse models for a variety of tumors, using Cre/Lox mediated switching of tumor suppressor genes and oncogenes. Both transgenesis and somatic gene transfer are employed to express Cre recombinase and other genes or shRNAs in a regulatable fashion. The methodology enables us to switch multiple oncogenes and/or tumor suppressor genes within cells in vivo at a defined time and to monitor the relevance of these genes for tumor initiation and progression. The induction of highly specific tumors within a narrow time window permits us to correlate specific genetic lesions with distinct tumor characteristics. The general picture that transpires from these studies is that the mouse cancer models show closer resemblance to the human condition when they share the same mutations. By applying sensitive in vivo imaging techniques to follow tumor growth and metastatic spread in real time in animals we not only can follow tumor development longitudinally but also monitor response to genetic and pharmacological interventions.

Thoracic tumors
We focus on thoracic tumors: small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), squamous cell carcinoma (SCC) and mesothelioma. Using different sets of conditional tumor suppressor genes and oncogenes all the thoracic tumors can be induced specifically. When, for example,Rbandp53are inactivated specifically in lung, SCLC develops in nearly 100% of the mice. These tumors closely resemble human SCLC and are often heterogeneous consisting of different cell types, with either neuroendocrine or mesenchymal features. Subcutaneous grafting of each of the cell types independently gave rise to localized tumors that retained the features of the inoculated cells. However, grafting mixtures resulted in local growth as well as metastasis of the neuroendocrine cells to liver indicating that the non-neuroendocrine cells in the graft endowed the neuroendocrine cells with metastatic potential. This shows functionality of tumor cell heterogeneity. We try to uncover the underlying signaling.

An important question in our studies is the role of the cell-of-origin of these tumors. We address this by switching oncogenes and tumor suppressor genes specifically in Clara cells, Alveolar type II cells, neuroendocrine cells, basal epithelial cells of lung and in the mesothelial lining of the thoracic cavity. It appears that both the cell-of-origin and the introduced genetic lesions are critical determinants of the phenotypic characteristics of the resulting tumors. We are inquiring whether the cell of origin might also explain some of the unique features of the tumor subtypes in humans.

We are making these models more versatile by re-derivation of ES cells from them and equipping these with DNA exchange cassettes that allow us to swiftly introduced additional oncogenes, inducible shRNAs or reporters in order to test their contribution to the tumor phenotype or to the response to intervention. In this way we can also quickly evaluate the importance of putative cancer genes found by the sequencing DNA of human cancers. Furthermore, transposon-based insertional mutagenesis is conducted in these models to identify genes and pathways that strongly synergize with the driver mutations genetically inserted in these models. This will providfe us with clues what to look for in the cognate human tumors.

Parallel to these experiments we are developing protocols to establish cultures from human mesothelioma and to propagate these tumors as patient derived xenografts (PDX).

Co-workers

silhouette_geen_foto_thumb_man.jpg

Paul Krimpenfort

Academic Staff

Experience

My main scientific interest is the tumor suppressive function of the Ink4 gene family encoding the Cdk4/6 inhibitors p15Ink4b, p16Ink4a, p18Ink4c and p19Ink4d. Since Cdk4 and Cdkn6 stimulate G1 progression by phosphorylating Rb, the primary effect of Ink4 inactivation is thought to be the loss of cell cycle control. However, apart from their role in cell cycle control recent observations suggest the implication of the Ink4 proteins in tumor cell behaviour e.g. migration and invasiveness. An important issue is if and to what extent the Ink4 genes are redundant.

In addition, I am also involved in the NKI Transgenic Facility and I am a member of the Animal Experiment Committee (DEC) of the NKI.

Close this window
Badhai, Jitendra.jpg

Jitendra Badhai,Ph.D

Postdoctoral Fellow

Experience

I have completed my PhD in clinical genetics from Uppsala University, Sweden and now I am working as a postdoctoral fellow at Division of Molecular Genetics, Netherlands Cancer Institute. I am particularly interested in making better mouse model and finding key driver genes in mesothelioma and small cell lung cancer (SCLC). I am employing piggyBac (PB) transposon mutagenesis in mice and integrative analysis approach in mouse tumor to find driver genes in mesothelioma and SCLC.

 

 

Close this window
Bombardeli, Lorent.jpg

Lorenzo Bombardelli, Ph.D

Postdoctoral Fellow

Experience

I have been interested for a long time in mouse models of cancer and tumor microenvironment. During my PhD I worked on cell polarity and secretory pathways in pancreatic cancer and subsequently on how the crosstalk between adhesion molecules and tyrosine kinase receptors accelerates ovarian cancer dissemination.

My current work is focused on the pharmacogenomics of small-cell lung cancer (SCLC). Thanks to the transgenic models developed in the lab, I am testing new therapeutic combinations and investigate mechanisms of drug resistance in myc-driven SCLC.

 

 

Close this window
silhouette_geen_foto_thumb_vrouw.jpg

Guistina Ferone, Ph.D

Postdoctoral fellow

Experience

I gained my Ph.D. in Biochemistry and Molecular and Cellular Biology in Italy then, on July 2012, I joined the Berns lab. I consider this a great opportunity: the NKI environment is very challenging; moreover the group has extraordinary tools that make you comfortable to approach a wide range of topics. I am particularly interested in studying lung Squamous Cell Carcinoma through the generation and characterization of mouse models carrying inducible genetic lesions found in human tumors. To hit uniquely basal cells of the bronchial epithelium (cell-of-origin of SCC) I use intratracheally delivered viruses carrying Cre recombinase under specific promoters.  

 

Close this window
silhouette_geen_foto_thumb_vrouw.jpg

Ekaterina Semenova,Ph.D

Postdoctoral Fellow

Experience

I have received my PhD in Molecular Biology from Princeton University. Before joining NKI, I worked in the field of skin regeneration, inflammation and gene therapy.  I am interested in developing novel lineage tracing and visualization tools to identify and track lung stem cells and tumor initiating cells using in vivo and ex vivo platforms.

 

 

 

 

 

Close this window
silhouette_geen_foto_thumb_man.jpg

Rajith Bhaskaran, Ph.D

Postdoctoral Fellow

Experience

I completed my PhD at VIT University India. There I studied how point mutations in protein kinases can result in structural changes that result in drug resistance.

Currently I work on the identification of putative oncogenic drivers in small cell lung cancer by comparing the genomic aberrations/mutations found in human small cell lung cancer with those in the cognate mouse models using NextGen Sequencing.






Close this window
silhouette_geen_foto_thumb_man.jpg

Jan Paul Lambooij

Lab manager & Technical Staff

Experience

I am a technician in the group of Ton Berns since 2003. I got my article 12 in 2009.
 

Close this window
silhouette_geen_foto_thumb_vrouw.jpg

Hilda de Vries Ph.D

Postdoctoral Fellow

Experience

After I finished as a PhD student in the field of DNA damage, I am joining the Berns lab since 2004 and became very much interested in Malignant Mesothelioma (MM). Ever since, I created anin vitroapproach to study both normal and malignant (mouse) mesothelial cells that I now use in combination within vivomodel(s) to study the cell of origin and drug pathways. Besides this, I also work on the development of a PDX model for MM. This field of translational research gives me the opportunity to contribute to a better survival of MM patients.  

 

 

Close this window
silhouette_geen_foto_thumb_man.jpg

John Zevenhoven

Technical Staff

Experience

After 10 years working as a histopathology technician on a Pathology department of a hospital I made a move in the year 2000 to the research and started working at the NKI at the department of Molecular Genetics. Here I work on several projects were my expertise can be valuable to different researchers.

My job involves all kind of (immuno)histological techniques, optimizing antibodies on fresh, frozen and paraffin material. This by means of bright light microscopy or digital microscopy with a confocal laserscanner.

 

Close this window
Corijnsen, Miranda.jpg

Miranda Cozijnsen

Technician

Experience

For the past year I have been working in the group of Prof. Anton Berns (Molecular Genetics) on several different mouse tumor (lung and mesothelioma) models. Recently I got the opportunity to start working in the Transgenic Mouse Facility of the Mouse Cancer Clinic for Research and Aging. In this setting I am involved in microinjection of mouse embryos, IVF, sperm and embryo freezing and validation of new mouse models. After finishing my education (HLO) in Utrecht working with genetically engineered mice always has had my preference. And now to be able to do so at the NKI is a dream come true.

Close this window
silhouette_geen_foto_thumb_man.jpg

Jan van der Vliet

Technical Staff

Experience

I work in the lab of Anton Berns since September 2013. In het lab I work on the different models this group has for small cell lung cancer and mesothelioma.

 

 

 

 

Close this window
silhouette_geen_foto_thumb_vrouw.jpg

Fina van der Ahé

Technical Staff

Experience

Since 2001 I have been working as a biotechnician in the group of Prof. Anton Berns and in the Mouse clinic transgenesis unit. My job involves microinjection, genotyping, and sperm cryopreservation.

 

 

 

 

Close this window
Error parsing XSLT file: \xslt\NKIGroup/UpdatesBlock.xslt

Key publications View All Publications

  • Mouse models for lung cancer

    Mol Oncol. 2013 Apr;7(2):165-77

    Kwon MC, Berns A.

    Link to Pubmed
 
 

Recent publications View All Publications

  • Excellent translational research in oncology: A journey towards novel and more effective anti-cancer therapies.

    Mol Oncol. 2016 May;10:645-51

    Rajan A, Berns A, Ringborg U, Celis J, Ponder B, Caldas C, Livingston D, Bristow RG, Hecht TT, Tursz T, van Luenen H, Bono P, Helander...

    Link to Pubmed
  • WntDown,Tumors WindUp?

    Cell 2016 161:1494-1496

    Krimpenfort P, Berns A.

    Link to Pubmed
 

Contact

  • Office manager

    Marij Degen

  • E-mail

    m.degen_AT_ nki.nl

  • Telephone Number

    +31 (0)20 512 9134

silhouette_geen_foto_thumb_vrouw.jpg

Donate

'Research for the benefit of cancer patients'

Support us
Share this page