Biochemistry: Thijn Brummelkamp
Thijn Brummelkamp, Ph.D.Group leaderAbout Thijn Brummelkamp
Research interest: Experimental biomedical genetics
Experimental genetics provides a powerful window into complex biological processes. Recently we have developed an entirely novel genetic model system to expand the toolbox for genetics in human cells. This method enables efficient inactivation of human genes by a single mutation using insertional mutagenesis in cells that are haploid or near-haploid. We have used haploid genetic screens to identify genes that play a role in human disease. This led to the identification of the lysosomal cholesterol transporter NPC1 as the long-sought intracellular receptor for Ebola virus, the first cellular entry receptor used by a Clostridium difficile toxin and numerous host factors needed for construction of the Lassa virus entry receptor. Beyond its application in infectious disease we use haploid genetics to identify genes important for drug-action or to search for cancer cell vulnerabilities.
In parallel, we are also interested in understanding the mechanisms that control organ size. How tissues stop growing upon reaching a certain size remains a mystery in biology. This is likely relevant for tumorigenesis because tumor cells are able to bypass normal growth control and continue to proliferate unabated.Drosophila genetics has increased our understanding of the biology of organ size control, and the Hippo signaling pathway has emerged as a key regulator. Interestingly, all the components of the Hippo pathway are conserved in mammals and some have been implicated in cancer. We use genetic mouse models and biochemical methods to address how this signaling pathway regulates tissue size in mammals and how it contributes to tumorigenesis.
After studying Cancer Genomics & Developmental Biology at Utrecht University I started my PhD training in 2010 in Thijn's lab at the Whitehead Institute for Biomedical Research and subsequently at the NKI. My main topic of interest is employing and adapting haploid genetic screening techniques to identify cancer cell vulnerabilities.
Over the course of my studies in Human Biology at the Philipps University of Marburg, I worked with Prof. Martin Eilers (Biozentrum, Würzburg), Prof. Rolf Müller (IMT, Marburg) and Prof. Tomas Ekström (Karolinska Institute, Stockholm). My thesis was prepared in the lab of Prof. Robert Weinberg (Whitehead Institute, Cambridge) on the subject of tumor-stroma interactions. My current interest lies in studying cancer cell vulnerabilities and host-pathogen interactions.
After obtaining my Masters degree at Utrecht University I joined the Brummelkamp group. During my PhD I aim to find new regulatory components of the currently poorly described Hippo pathway using haploid genetics. Herewith I hope to contribute to our understanding of the role of Hippo signaling in both organ size regulation as well as carcinogenesis.
After finishing my masters degree (Cancer Genomics & Developmental Biology) at Utrecht University I started my PhD training in 2010 in Thijn's lab at the Whitehead Institute and subsequently at the NKI. My main topic of interest is employing haploid genetic screening techniques to identify viral host factors in the human cell.
Lisa van den Hengel
After I graduated in Medical Biology at the University of Groningen, I followed a PhD trajectory at the Einthoven Laboratory for Experimental Vascular Medicine at the Leiden University Medical Center. In 2012, I started to work in the Brummelkamp lab where I participate in research projects that focus on the identification of host factors required for viral infection.
Born and raised in the Netherlands, I obtained my Master's degree in Biomedical Sciences from Utrecht University in 2004. I did my PhD, focused on coronavirus-host interactions, at the same University in the Virology group of Peter Rottier.
After graduating in September 2009, I started working in the lab of Sean Whelan at Harvard Medical School in Boston (USA), where I performed research on the cell entry mechanisms exploited by different negative-strand RNA viruses.
In August 2013 I joined the Brummelkamp lab where I am currently using haploid genetic screening technology to uncover new virus entry strategies.
I studied biochemistry at the University of Bielefeld and performed my diploma thesis at the Heart and Diabetes Center North Rhine-Westphalia in Bad Oeynhausen. During my PhD in the group of Prof. Martin Eilers (University of Wuerzburg) I focused on the Protein regulation of the transcription factor N-Myc in neuroblastoma. In September 2013 I started to work in Thijn's lab as a postdoctoral fellow.
I studied life sciences in Utrecht at the Hogeschool Utrecht with a specialization in zoology. After my first internship at Universiteit Utrecht, working on sexual side effects of SSRI's in mice, I did my final internship at the NKI. At the NKI I did research on PARP inhibitors in BRCA1 deficient mammary tumors in the laboratory of Jos Jonkers. I later returned to the NKI working on different projects involving mouse genetics in the groups of Thijn Brummelkamp and Fred van Leeuwen
Research updates View All Updates
Thijn Brummelkamp receives the EMBO Gold Medal 2013
The EMBO Gold Medal is awarded annually to scientists under the age of 40 for outstanding contributions to the life sciences in Europe.Thijn Brummelkamp receives the EMBO Gold Medal 2013
Marie Curie Fellowship has been awarded to Matthijs Raaben
Matthijs Raaben, postdoc in the research group of Thijn Brummelkamp, has been awarded a Marie Curie Fellowship by the European Union. The fellowship aims to stimulate the career of young, talented researchers within the EU.
Key publications View All Publications
Ebola virus entry requires the cholesterol transporter Niemann-Pick C1
Nature. 2011 Aug 24;477(7364):340-3.
Carette JE, Raaben M, Wong AC, Herbert AS, Obernosterer G, Mulherkar N, Kuehne AI, Kranzusch PJ, Griffin AM, Ruthel G, Dal Cin P, Dye JM, et al.Link to PubMed
Haploid genetic screens in human cells identify host factors used by pathogens
(2009) Science 326,1231-1235
Carette JE, Guimaraes CP, Varadarajan M, Park AS, Wuethrich I, Godarova A, Kotecki M, Cochran BH, Spooner E, Ploegh HL, Brummelkamp TR. et al.Link to Pubmed
Recent publications View All Publications
Lassa virus entry requires a trigger-induced receptor switch
Science. 2014 Jun 27;344(6191):1506-10
Jae LT, Raaben M, Herbert AS, Kuehne AI, Wirchnianski AS, Soh TK, Stubbs SH, Janssen H, Damme M, Saftig P, Whelan SP, Dye JM, Brummelkamp...Link to Pubmed
Deciphering the glycosylome of dystroglycanopathies using haploid screens for lassa virus entry
(2013) Science 26, 479-83
Jae, LT, Raaben, M, Riemersma, M, van Beusekom, E, Blomen, VA, Velds, A., Kerkhoven, RM, Carette, JE, Topaloglu, H., Meinecke, P, Wessels,...Link to Pubmed
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