Ph.D., Professor of Medical Systems Biology
Genome-Scale Biology Research Program
& Department of Pathology, Haartman institute, University of Helsinki,
Rm B502b, P.O. Box 63 (Haartmaninkatu 8)
FI-00014 University of Helsinki, Finland
Tel. +358-9-1912 5556
Professor Jussi Taipale holds a joint appointment at the University of Helsinki, and at Karolinska Institutet. The Taipale lab at the University of Helsinki is part of the Academy of Finland's Center of Excellence in Cancer Genomics (2012-2017). Our group is interdisciplinary, and composed of both biomedical and computer scientists. Our main scientific interest is in understanding of how growth factors and oncogenes drive cell proliferation.
Organ specific growth control remains one of the major, unresolved questions in developmental biology. It is not understood what determines organ size and shape, and it is not clear why tumors arising in different tissues harbor different oncogenic mutations. Much of what we do know about physiological mechanisms controlling cellular growth in mammals has been revealed by human cancer genetics. These studies have revealed that a large number of genes can contribute to aberrant cell growth. More than 350 genes have been linked to cancer and mutations found in cancer are often cell type specific, suggesting that different pathways in different cell lineages are coupled to the cell cycle machinery. Our hypothesis is that the problems of organ-specific growth control and specificity of oncogenes to particular tumors represent two sides of the same coin; that is, mutations in tumors are tissue specific, because tumors arise by the most economical mutagenic route, aberrantly activating the organ-specific growth mechanisms.
We are taking a systems-biology approach to understand how tissue-specific factors collaborate with oncogenic signals to drive cell proliferation. For this purpose, we have developed computational and experimental methods to identify direct target genes of oncogenic transcription factors that are commonly activated in major forms of human cancer. In addition, we have used high-throughput RNAi screening to identify genes required for cell cycle progression. Combining these two sets of data allows identification of specific transcription factors and gene regulatory elements which drive growth in particular tissues and tumor types.
Current lines of work in the laboratory include:
1. Development of computational tools that can model transcription factor binding to DNA and predict gene expression based on genome sequence (Hallikas, 2006; Jolma, 2013).
2. Development of advanced methods based on next generation sequencing to study transcription (Jolma, 2010; Kivioja, 2012)
3. Identification of common targets of oncogenic transcription factors using computational tools and methods such as chromatin immunoprecipitation followed by sequencing (ChIP-seq; Wei, 2010)
4. Functional characterization of cancer predisposition alleles that map to gene regulatory regions (Tuupanen, 2009; Sur 2012).
3. Genome-wide identification of genes driving proliferation of normal and tumor cells (Bjorklund, 2006; Varjosalo, 2008; Bonke 2013)
- Jolma, A., Yan, J., Whitington, T., Toivonen, J., Nitta, K.R., Rastas, P., Morgunova, E., Enge, M., Taipale, M., Wei, G., Palin, K., Vaquerizas, JM., Vincentelli, R., Luscombe, NM., Hughes, TR., Lemaire, P., Ukkonen, E., Kivioja, T. and Taipale, J. DNA-Binding Specificities of Human Transcription Factors. Cell. 152:327-39, 2013.
- Bonke, M., Turunen, M., Sokolova, M., Vähärautio, M., Kivioja, T., Taipale, M., Björklund, M. and Taipale, J. Transcriptional networks controlling the cell cycle. G3 (Bethesda) 3:75-90, 2013.
- Sur, I.K., Hallikas, O., Vähärautio, A., Yan, J., Turunen, M., Enge, M., Taipale, M., Karhu, A., Aaltonen, L.A. and Taipale, J. Mice Lacking a Myc Enhancer That Includes Human SNP rs6983267 Are Resistant to Intestinal Tumors. Science. 338:1360-3, 2012.
- Kivioja, T.#., Vähärautio, A..#, Karlsson, K., Bonke, M., Enge, M., Linnarsson, S., and Taipale, J.Counting absolute number of molecules using unique molecular identifiers. Nature Methods 9:72-4, 2012. (# contributed equally, in alphabetic order)
- Jolma, A., Taipale, J. Methods for Analysis of Transcription Factor DNA-Binding Specificity In Vitro. Subcell Biochem. 52:155-173, 2011.
- Wei G.-H., Badis, G., Berger, M. F., Kivioja, T., Palin, K., Enge, M., Bonke, M., Jolma, A., Varjosalo, M., Gehrke, A. R., Yan, J., Talukder, S., Turunen, M., Taipale, M., Stunnenberg, H. G., Ukkonen, E., Hughes, T. R., Bulyk, M. L., and Taipale, J. Genome-Wide Analysis of ETS Family DNA-Binding in vitro and in vivo. EMBO J. 29:2147-2160, 2010.
- § Jolma, A., Kivioja, T., Toivonen, J., Cheng, L., Wei, G.-H., Enge, M., Taipale, M.,Vaquerizas, J. M., Yan, J., Sillanpää, M. J., Bonke, M., Palin, K., Talukder, S., Hughes, T. R., Luscombe, N. M., Ukkonen, E., and Taipale, J. Multiplexed massively parallel SELEX for characterization of human transcription factor binding specificities. Genome Res. 20:861–873, 2010.
- Tuupanen, S., Turunen, M., Lehtonen, R., Hallikas, O., Vanharanta, S., Kivioja, T., Björklund, M., Wei, G.-H., Yan, J., Niittymäki, I., Mecklin, J.-P., Järvinen, H., Ristimäki, A., Di-Bernardo, M., East, P., Carvajal-Carmona, L., Houlston, R. S., Tomlinson, I., Palin, K., Ukkonen, E., Karhu, A., Taipale, J., and Aaltonen, L. A. The common colorectal cancer predisposition SNP rs6983267 at chromosome 8q24 confers potential to enhanced Wnt signaling. Nature Genetics 41:885-890, 2009.
- Varjosalo, M.#, Björklund, M.#, Cheng, F., Syvänen, H., Kivioja, T., Kilpinen, S., Sun, Z., Kallioniemi, O., Stunnenberg, H. G., He, W.-W., Ojala, P., and Taipale, J. Application of active and kinase-deficient kinome collection for identification of kinases regulating Hedgehog signaling. Cell 133: 537-548, 2008. (# contributed equally, in reverse alphabetic order)
- Björklund, M. #, Taipale, M. #, Varjosalo, M., Saharinen, J., Lahdenperä, J., and Taipale, J.Identification of pathways regulating cell size and cell cycle progression by RNAi. Nature439:1009-1013, 2006. (# contributed equally, in alphabetic order)
- Hallikas, O.#, Palin, K.#, Sinjushina, N., Rautiainen, R., Partanen, J., Ukkonen, E., and Taipale, J. Genome-wide prediction of mammalian enhancers based on high-throughput analysis of transcription factor binding affinity. Cell 124:47-59, 2006. (# contributed equally, in alphabetic order)
For a complete list of last author publications, see here.
For a complete list of publications, see here.
We have positions available immediately for both Ph.D. students and post-docs, if you are interested in our research please send your CV along with a motivation letter to firstname.lastname@example.org.
July 10, 2013
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