The main scientific questions addressed in our laboratory relate to the understanding of molecular mechanisms that control gene regulation through the use of high-throughput biology to characterize transcription factor binding specificities and sites in human cancer cells. TFs are analyzed both alone, and in combination with other TFs and scaffolding proteins such as the mediator complex. The resulting knowledge is then applied to the interpretation of large data sets such as whole cancer genomes, and genome-wide association studies that have revealed genomic regions associated with a wide variety of diseases, including heart disease, diabetes and different types of cancer. The work in the laboratory is interdisciplinary, and has impact both to basic scientific understanding of gene regulation, and to mechanisms of formation of cancer and other diseases.

The specific objectives of our research are the following:
1 To identify mechanisms that govern transcription factor binding in vitro and in live cells
2 To use the resulting information in the interpretation of cancer genomes and genome wide-association studies
3 To validate the findings in mouse genetic models

About the laboratory
Professor Jussi Taipale got his Ph.D. from the University of Helsinki in 1996, and continued with postdoctoral work at the University of Helsinki and at Johns Hopkins University (Baltimore, MD, USA). He has headed an independent research laboratory since 2003, focusing on systems biology of growth control and cancer. The main expertise of the Taipale group is high-throughput screening using cDNA and RNA interference, computational and experimental methods to identify causative regulatory mutations in non-protein coding DNA and to analyze genetic networks. In addition, Taipale group has extensive expertise on mouse models of gene and regulatory region function. The group at Karolinska Institutet consists of four senior scientists, six postdoctoral fellows, two graduate students a research engineer and two technicians. In addition, to coordinate the EU FP7 collaborative project SYSCOL, we have a project manager and a project administrator.



Yan et al., Cell 2013

Here, we have developed a high-throughput ChIP-seq method, and mapped the binding patterns of hundreds of TFs in a human cell-line. Global analysis of the binding patterns indicate that TF binding cluster to a much larger degree than previously anticipated, with TF clusters occupying less than 1% of the genome. The TF clusters were strongly enriched in binding motifs, evolutionary conserved, and predictive of gene... >>

Jolma et al., Cell 2013

In this work, we describe binding specificity models for the majority of all human TFs, approximately doubling the coverage compared to existing systematic studies. Our results also reveal additional specificity determinants for a large number of factors for which a partial specificity was known before, including a commonly observed A- or T-rich stretch flanking core-binding motifs. Global analysis of the data reveals that homodimer orientation... >>

Sur et al., Science 2012

In this work, we generated mice deficient in Myc-335, a putative MYC regulatory element that contains rs6983267, a SNP accounting for more human cancer-related morbidity than any other genetic variant or mutation. In Myc-335 null mice, Myc transcripts were expressed in the intestinal crypts in a pattern similar to that in wild-type mice but at modestly reduced levels. The mutant mice displayed no overt phenotype... >>

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