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Molecular Genetics: John Hilkens

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John Hilkens, Ph.DGroup Leader

About John Hilkens

Research Interest

The main research interest of the group is to identify genes and signaling pathways relevant for breast cancer. Transformation of a normal cell into a fully malignant cell requires several sequential genetic changes affecting key genes controlling various essential cellular pathways involved in growth and development. Complete knowledge of the genes and the pathways they control is essential for the development of more effective novel therapeutic strategies.

Although a large number of genes that are involved in breast and other cancers has been discovered, the picture is far from complete. Insertional mutagenesis (IM) in mouse models is one of the most efficient tools to uncover cancer genes. The aim of John Hilkens' laboratory is to identify and study novel genes involved in breast cancer and unravel the collaborating genetic pathways leading to breast cancer and breast cancer progression using high throughput insertional mutagenesis in mouse models.

During recent years the group of John Hilkens has performed MMTV mediated insertional mutagenesis studies in wild-type mice and in various mouse models for human breast cancer including Her2 transgenic mice. A number of novel candidate cancer causing genes have been identified and validated as oncogenes. Presently, the group is uncovering the function of these genes, particularly the molecular pathways these genes deregulate in the cancer cell. This knowledge on the cancer genes and their downstream oncogenic pathways can lead to the discovery of novel drug targets and treatment options, and to more personalized therapy for patients with breast cancer, and potentially also with other types of cancer.

An additional line of research concerns the biological function of cell surface associated mucins, notably MUC1 (also designated Episialin, MAM-6, EMA, CA 15-3 antigen, CD 227), which is frequently highly upregulated in various types of cancers and has been implicated in breast cancer progression. Although we have shown that MUC1 reduces cell-cell and cell-matrix adhesion and promotes metastasis due to shielding of the adhesion receptors by its extremely elongated extra cellular domain the precise biological function of this glycoprotein still has not been fully elucidated.

Key publications View All Publications

  • Analysis of Tumor Heterogeneity and Cancer Gene Networks Using Deep Sequencing of MMTV-Induced Mouse Mammary Tumors.

    PLoS One. 2013 May 14;8(5):e62113

    Klijn C, Koudijs MJ, Kool J, Ten Hoeve J, Boer M, Lagcher W, de Moes J, Akhtar W, van Miltenburg M, Vendel-Zwaagstra A, Reinders MJT, Adams et al.

    Link to Pubmed
  • MMTV insertional mutagenesis identifies genes, gene families and pathways involved in mammary cancer.

    Nat Genet. 2007; 39: 759-69.

    Theodorou V, Kimm MA, Boer M, Wessels L, Theelen W, Jonkers J, Hilkens J.

    Link to Pubmed
 
 

Recent publications View All Publications

  • Chromatin landscapes of retroviral and transposon integration profiles.

    PLoS Genet. 2014 Apr 10;10

    de Jong J, Akhtar W, Badhai J, Rust AG, Rad R, Hilkens J, Berns A, van Lohuizen M, Wessels LF, de Ridder J

    Link to Pubmed
  • Analysis of Tumor Heterogeneity and Cancer Gene Networks Using Deep Sequencing of MMTV-Induced Mouse Mammary Tumors

    PLoS One. 2013; 14;8:e62113

    Klijn C, Koudijs MJ, Kool J, Ten Hoeve J, Boer M, Lagcher W, de Moes J, Akhtar W, van Miltenburg M, Vendel-Zwaagstra A, Reinders MJT,...

    Link to Pubmed
 

Contact

  • Office manager

    Marij Degen

  • E-mail

    m.degen_AT_ nki.nl

  • Telephone Number

    +31 (0)20 512 9134

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