Molecular Cell Biology 1

Cancer Signaling Networks and Molecular Therapeutics (5.03.01)

Principal investigators

Prof. Dr. P. ten Dijke, Dr. D.A. Baker, Dr. A.G. Jochemsen, Dr. A.C.O. Vertegaal, Dr. J.A.F. van Dam, Dr. K. Szuhai

Aim and focus

The aim of this research program is to understand how intra- and inter-cellular (biochemical) interactions drive tissue growth and differentiation, how these processes become corrupted in cancer, and how this information can be translated into therapeutic intervention. To this end, we take a multi-disciplinary approach by employing leading edge technologies for forward and reverse genetic manipulation of human cells, exon and genome wide sequencing, molecular imaging, proteome-wide mass spectrometry analyses of normal and abnormal human cells as well as mouse and zebra fish model systems for  in vivo studies. We investigate the molecular mechanisms of various related hallmarks of cancer, including cell proliferation, genome instability, migration and invasion, angiogenesis and metastasis. Our complementary and overlapping research lines focus on the identification of novel regulators of the TGF-beta signal transduction pathway as well as the intercellular Notch-Delta pathway, p53 regulation and the role of post-translational modifications such as phosphorylation, sumoylation and ubiquitination in signal transduction, cell cycle progression and the DNA damage response. The identification of tumor specific changes allow the development of diagnostic tests and open avenues for searching for new treatments. For this, unique cell lines are established that may serve as the basis of compound screening efforts. We also apply our insights of cancer in the development of novel therapies of benign diseases, which share certain aspects of cancer.

To advance our knowledge towards therapies that target each one of these hallmarks of cancer, we have forged national and international collaborations with the aim of developing a comprehensive anti-cancer strategy. This fits within the LUMC priority area Cancer Pathogenesis and Therapy (CPT). Locally, we have close ties with groups within MCB focused on cell-based therapies, clinical departments of the LUMC such as Pathology, Gastroenterology, Ophthalmology and Clinical Oncology. More broadly, we work with the University of Leuven, the LACDR, the Netherlands Cancer Institute and the Ludwig Institute for Cancer Research.