PI: Marcel van Vugt, PhD
Marcel van Vugt ('s-Hertogenbosch, 1977) studied Medical Biology at the Faculty of Medicine of the University of Utrecht, and obtained his PhD at the division of Molecular Biology at the Netherlands Cancer Institute (NKI-AvL) and the Medical Oncology department of the University Medical Centre Utrecht (UMCU) in the laboratory of Prof. Dr. Rene Medema. Here, he studied the role of Polo-like kinase-1 (Plk1) during the cell cycle. His PhD research project described the requirement for Plk1 to build functional mitotic spindles. In addition, his work led to the finding that Polo-like kinase-1 controls the recovery of human cancer cells after treatment with genotoxic chemotherapeutics.
Following his graduation in 2005, he was awarded an EMBO long term fellowship to study the regulation of the DNA damage checkpoint by cell cycle kinases in the laboratory of Michael B. Yaffe at the David H. Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology (MIT, Cambridge USA). To this end, he used a combination of bioinformatics and biochemical analyses to predict kinases-substrate interactions that modify the function of the DNA damage checkpoint.
Now, Marcel van Vugt is Adjunct Professor of Molecular Oncology at the Laboratory for Medical Oncology. He was awarded independent researcher grants from the Dutch organization for scientific research (NWO-VENI, NWO-VIDI) and personal funding for translational research from the Dutch Cancer Society (KWF) and European Research Council (ERC Consolidator). His research aims at finding regulatory pathways that control the cellular responses to DNA damage. Using a combination of genetics, biochemistry and microscopy, he studies molecular interactions, of which the clinical implications are subsequently tested using patient-relevant models.
DNA damage checkpoint and DNA repair pathways in cancer
Our DNA is constantly damaged by external factors, and persistent DNA damage can result in cancer. In order to prevent this, cells are equipped with pathways that respond to DNA damage, stop ongoing proliferation and activate DNA repair. These pathways are collectively called the DNA damage checkpoint. Paradoxically, besides being a cause of cancer, DNA damage is also a mainstay in the treatment of cancer. To kill cancer cells, radiotherapy and chemotherapy induce high levels of DNA damage. However, the overall inefficiency of radio/chemotherapy still points to ample room for improvement. The ability of cancer cells to repair therapy-induced DNA damage clearly contributes to this inefficiency. An appealing approach to sensitize cells for radio/chemotherapy is therefore to target the DNA damage checkpoint. But it is currently unclear how the DNA damage checkpoint can be modulated to improve the responses to radio/chemotherapy.
In our research, we use biochemical tools and microscopy to study how the DNA damage checkpoint functions in normal and cancer cells. Our main interest centers around the question how the DNA damage checkpoint is regulated, and we specifically focus on cell cycle regulation as an important modifier of DNA damage checkpoint function. In addition, we investigate how we can optimallly monitor the DNA damage checkpoint in cancer tissue, and which DNA damage checkpoint components may be efficient targets for additive treatment during cancer therapy.
For further information on the projects and for possibilities to join the lab, please contact Marcel van Vugt
- Rolf de Boer - Postdoc
- Anne Margriet Heijink - Postdoc (joined with Peter Lansdorp)
- Pepijn Schoonen - PhD student
- Sergi Guerrero-Llobet - PhD student
- Stephanie van Gijn - PhD student
- Colin Stok - PhD student
- Francien Talens - PhD student
- Marieke Everts - Technician
Esméé Joosten - Technician
- Elles Wierenga - Technician
- Fabioloa Zuchi - MSc student
- Wellington Mardoqueu Candido - MSc student
- Femke Bakker - BSc student
- van Vugt MA . Shutting down the power supply for DNA repair in cancer cells. J Cell Biol. 2017 Jan 25. pii: jcb.201701026.
- Heijink AM, Blomen VA, Bisteau X, Degener F, Matsushita FY, Kaldis P, Foijer F, van Vugt MA. A haploid genetic screen identifies the G1/S regulatory machinery as a determinant of Wee1 inhibitor sensitivity. Proc Natl Acad Sci USA. 2015;112:15160-5.
- Hengeveld RC, de Boer HR, Schoonen PM, de Vries EG, Lens SM, van Vugt MA. Rif1 is required for resolution of ultrafine DNA bridges in anaphase to ensure genomic stability. Dev Cell. 2015;34:466-74.
- Krajweska M, Fehrmann RS, Schoonen PM, Labib S, de Vries EG, Franke L, van Vugt MA. ATR inhibition preferentially targets homologous recombination-deficient tumor cells. Oncogene. 2015;34:3474-81.
- Fehrmann RS, Karjalainen JM, Krajewska M, Westra HJ, Maloney D, Simeonov A, Pers TH, Hirschhorn JN, Jansen RC, Schultes ES, van Haagen HH, de Vries EG, te Meerman GJ, Wijmenga C, van Vugt MA, Franke L. Gene expression analysis identifies global gene dosage sensitivity in cancer. Nat Genet. 2015;47:115-25.
- Lafranchi L, de Boer HR, de Vries EG, Ong SE, Sartori AA, van Vugt MA. APC/C(Cdh1) controls CtIP stability during the cell cycle and in response to DNA damage. EMBO J. 2014;33:2860-79.
- van Vugt MA , Gardino AK, Linding R, Ostheimer GJ, Reinhardt HC, Ong SE, Tan CS, Miao H, Keezer SM, Li J, Pawson T, Lewis TA, Carr SA, Smerdon SJ, Brummelkamp TR, Yaffe MB. A mitotic phosphorylation feedback network connects Cdk1, Plk1, 53BP1, and Chk2 to inactivate the G(2)/M DNA damage checkpoint. PLoS Biol. 2010;8:e1000287.
- Linding R, Jensen LJ, Ostheimer GJ, van Vugt MA, Jørgensen C, Miron IM, Diella F, Colwill K, Taylor L, Elder K, Metalnikov P, Nguyen V, Pasculescu A, Jin J, Park JG, Samson LD, Woodgett JR, Russell RB, Bork P, Yaffe MB, Pawson T. Systematic discovery of in vivo phosphorylation networks. Cell. 2007;129:1415-26.
- Wilker EW, van Vugt MA, Artim SA, Huang PH, Petersen CP, Reinhardt HC, Feng Y, Sharp PA, Sonenberg N, White FM, Yaffe MB. 14-3-3sigma controls mitotic translation to facilitate cytokinesis. Nature. 2007;446:329-32.
- van Vugt MA , Brás A, Medema RH. Polo-like kinase-1 controls recovery from a G2 DNA damage-induced arrest in mammalian cells. Mol Cell. 2004;15:799-811.
|Last modified:||20 March 2017 09.44 a.m.|