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While the human genome has been sequenced, the function of the vast majority of the genes in our genome remains unknown. The next big challenge is to investigate the functions of individual genes, and to find what role they are playing in disease.
Brummelkamp has developed technologies to accelerate genetic analysis of mammalian cells. A 'stable RNA interference' process, which he and his colleagues first described, is now widely used to manipulate and study gene function in mammalian cells. Brummelkamp uses stable RNA interference to inhibit thousands of human genes, in order to find specific genes that play a role in human disease. More specifically, he employs the process to identify cancer cell vulnerabilities that can be targeted by new therapeutics.
As a training round for larger-scale RNAi screens to uncover gene function, Brummelkamp and colleagues first focused on a family of genes involved in ubiquitin removal, a biochemical reaction that is highly relevant for human cancer. Doing so they identified new functions for several of these genes, leading to detailed molecular insights into a poorly characterized form of hereditary skin cancer.
Brummelkamp also uses RNAi techniques to study not only how particular anti-cancer drugs work, but the underlying molecular mechanisms that enable certain cancers to resist many therapies over time.
He received his MS in biology from the Free University, Amsterdam, in 1998. He did his graduate research at The Netherlands Cancer Institute in the laboratory of Rene Bernards and received his PhD cum laude in 2003 from Utrecht University.
Selected Publications
Nijman, S.M.B., Huang, T., Dirac, A.M.G, Brummelkamp, T.R., D'Andrea, A. and Bernards, R. (2005) The de-ubiquitinating enzyme USP1 regulates the Fanconi Anemia pathway. Mol Cell 3: 331-339.
Berns, K, Hijmans, E.M., Mullenders, J., Brummelkamp, T.R., Velds, A., Heimerikx, M., Kerkhoven, R.M., Madiredjo, M., Nijkamp, W., Agami, R., Ge, W., Cavet, G., Linsley, P.S., Beijersbergen, R.L., and Bernards, R. (2004). A large-scale RNAi screen in human cells identifies new components of the p53 pathway. Nature 428: 431-437.
Brummelkamp, T.R., Nijman, S.M.B., Dirac, A.M.G. and Bernards, R. (2003). Loss of the cylindromatosis tumour suppressor inhibits apoptosis by activating NF-kB. Nature 424: 797-801.
Brummelkamp, T.R. and Bernards, R. (2003). New tools for functional mammalian cancer genetics. Nat Rev Cancer 3: 781-789.
Brummelkamp, T.R., Bernards, R., and Agami, R. (2002). A system for stable expression of short interfering RNAs in mammalian cells. Science 296: 550-3.
Brummelkamp, T.R., Bernards, R., and Agami, R. (2002). Stable suppression of tumorigenicity by virus-mediated RNA interference. Cancer Cell 2: 243-7. |
