main_staff
Principal Investigator

  • Professor of Medical Systems Biology, Director of Karolinska High Throughput Center Jussi Taipale
jussi

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 Taipale Lab at Karolinska Institutet consists of four senior scientists, eight postdoctoral fellows, three graduate students and two lab managers. To coordinate the EU FP7 collaborative project SYSCOL, we have a project manager and a project administrator. Our laboratory is also adjacent to the Karolinska High Throughput Center, which hosts one of the most advanced automated laboratories in the world.

Administration

  • Personal Assistant Emma Inns
  • Work: 08-524 811 81
IMG_0298

As PA to Professor Taipale, my work is extremely varied. I help Prof. Taipale with everything from preparing reports and grant applications to managing recruitment and budgetary issues. In addition, I work closely with all our lab members and the department to help ensure the smooth running of the administrative side of the lab.

Senior Scientists

  • PhD Ekaterina Morgunova
Ekaterina-Morgunova

Francis Crick once notably said “If you wish to understand function, study structure”, Roger D. Kornberg took this further by noting “Extension of the structure to atomic resolution will one day reveal the regulatory mechanism”.

To understand how DNA sequence controls gene expression, one must first understand the binding specificity of transcription factors (TF) to DNA and/or other TFs/proteins. Therefore, the major aim of my research is to use X-ray crystallography to study the molecular principles underlying the interactions between TF and TF/other proteins or between TF and DNA.

  • PhD Bernhard Schmierer
Bernhard-Schmierer

Cell growth (the gain of mass and size of an individual cell) is a highly regulated process that is usually closely linked to cell proliferation (the increase in cell number through cell division). The mechanisms that regulate cell growth and coordinate it with cell division are fundamental to cell biology and the development of cancer. Nevertheless, the current body of knowledge regarding size control is far from satisfactory, in particular for cells derived from multicellular organisms. Two major questions remain largely unanswered: First, how do cells sense and set their target mass and size? And secondly, how do they coordinate growth with cell division to maintain their target size over the generations? We are using loss of function screening by siRNA and by gene-trapping in haploid human cells to identify genes that are involved in setting a target size, and genes that couple cell growth and cell proliferation in order to maintain this target size over the generations. Working out how exactly cell size and mass feed back on cell proliferation will elucidate how these processes co-operate to bring about malignant growth.

  • PhD Inderpreet Sur
Inderpreet

My interest is focused on the transcriptional regulation of growth control and lineage specification with emphasis on the question of how these are tweaked to generate a cancerous cell. Based on our analysis of the Myc-335 enhancer we postulate that a cancer cell might rely on cancer-specific transcriptional switches (enhancers) for its growth. A comprehensive identification and understanding of these would be useful in designing targeted therapy against cancer cells. Towards this goal I am currently studying- 1) the contribution of enhancer elements upstream of c-MYC to cancerous growth using in vivo models and 2) function of transcription factor Klf5 in cellular fate specifications.

  • PhD Minna Taipale
Minna-Taipale

My long time interest is regulation of the cell cycle and more recently, cellular growth control. The aim is to understand how a normal cell cycle differs from a tumorigenic one. I am currently involved in high throughput siRNA screens of human cell cycle regulators where we have targeted approx 23 000 human genes in order to find those that have effect on cell cycle. Similarly, we have already targeted all Drosophila genes and are currently studying in a more detailed manner the transcriptional targets and protein-protein complexes of the Drosophila genes that had an effect on cell cycle progression or cellular growth. In addition, I have been involved in a collaboration searching for novel mutations from colorectal cancer patients by sequencing and overseeing that our next generation sequencers, two illumina HiSeqs, are working 24/7.

Post-docs

  • PhD Kashyap Dave
Kashyap

Understanding the gene regulation by transcriptional factors requires clear knowledge of exact binding sequence for transcriptional factors (TFs) in genome, variations in this sequence and its association with other proteins/factors. In my study I seek out genome wide precise binding site for TFs in colorectal cancer cell lines through the CHIP-Exo (chromatin immunoprecipitation followed by exonuclease treatment and sequencing) method. Further challenge would be to identify TFs associated with each predicted gene and its role in altered gene expression during pathological conditions. Working on one such model, we are pursuing the analysis of enhancer elements upstream of the c-Myc gene in mice and their role in carcinogenesis.

  • PhD Project Manager/Researcher Åsa Kolterud
asa_webpage

EU Project manager/researcher

Since November 2012 I have been managing EU projects for the Taipale Group.

I also develop in vivo models for functional analyses of a number of regulatory elements identified in regions correlated to increased risk of multiple types of cancers. The aim is to explore how these regulatory elements contribute to cancer cell growth and their potential as targets for treatment.

  • PhD Yimeng Yin
Yimeng

Recently, we have reported DNA-Binding specificities of most human transcription factors (TFs) using a high-throughput SELEX (HT-SELEX). Actually, TFs typically bind to only a small subset of their potential target sites in vivo, which is partly due to the co-operation among transcription factors. To analyze the effects of cooperation on DNA-Binding specificities of human TFs, Arttu Jolma has established a heterodimer HT-SELEX. In this method, two sequence specific DNA binding proteins, one that has a SBP (streptavidin binding peptide) and the other one that has a 3FLAG epitope, will be mixed together and then allowed to find their target sites from a pool of DNA ligands that contain a 40 base long randomized region. After purified from the pools through tandem purification by first SBP and then 3FLAG tagged protein, bound dsDNA ligands are subjected to Illumina sequencing. I will run heterodimer HT-SELEX together with Arttu for the foreseeable future.

  • PhD Ning (Nina) Wang
NINA webpage

I achieved my Ph.D. in January 2014 at Karolinska Institutet working on genetics of primary immunodeficiency disorders. I joined Taipale group as a new postdoctoral researcher in September 2014; my main research interests are enhancer elements and DNA (de)methylation. Using advanced technologies (e.g. whole genome bisulfite sequencing and the CRISPR/Cas9 system) and well-established data analyzing pipelines, hopefully we can open up new ways of understanding the mechanism of cancer development.

  • PhD Fangjie Zhu
Fangjie webpage

We have reported that transcription factor binding occurs in dense clusters. Since these clusters are enriched by known in vitro TF motifs, it is possible to predict the location of these clusters using motif matches. The accuracy of the prediction was found to be intimately related to the stringency level used. In order to optimise the stringency level for each TF, and in turn to make a better prediction for the location of the clusters, I hope to quantify the TFs in living cells and improve ChIP-Seq by using identical affinity tags for the different TFs.

  • PhD Eevi Kaasinen
Eevi Kaasinen. // Kuva: Markus Sommers, 18.3.2015, Helsinki, Biomedicum 1

I previously worked in the Tumor Genomics group / Center of Excellence in Cancer Genetics led by Professor Lauri Aaltonen at the University of Helsinki , and defended my PhD thesis in September 2014. In May of 2015 I moved to the Taipale group at Karolinska Institutet to work as a postdoctoral researcher. My specialty is genome-scale data analyses and high-throughput sequencing. The focus of my research in Aaltonen group was to identify genetic changes underlying hereditary diseases and uterine leiomyomas. Currently, my main interest is to model tumor development based on the ever increasing data from germline polymorphisms, somatic mutations, epigenetic changes, gene expression, transcription factor binding sites and in silico predicted regulatory elements.

  • PhD Sandeep Botla
IMG_0568 (2)

Tumors don’t follow a specific set of rules but they follow a theme “There is no one way of doing things”. That is, every tumor type plausibly even the sub clone within a single tumor uses different tools (genes/pathways) to attain a same phenotype: uncontrolled proliferation. This complicates the biology of cancer and makes it extremely difficult to design therapeutic strategies. Fortunately for us the focal points of many genes/pathways are the transcription factors (TF’s), which are fewer than the number of mutated genes in cancer therefore realistic targets for therapeutic options.

TF’s respond to the extracellular signal and transcribe genes needed for tumor cell maintenance and propagation. In cancerous cells the TF’s need to cope with the high rates of transcription to support fast dividing cells. This is where the DNA Cis-regulatory elements such as the enhancers play a crucial role.

Therefore my interest is to identify essential (without which a tumor cell cannot survive) transcription factors, functionally characterize, map their regulatory loci in the genome of multiple cancer types and use this information to design therapeutic strategies to combat cancer.

Graduate Students

  • Grad student Bei Wei
Bei_2

My scientific interest is mainly about the mechanisms of cell fate determination, especially in stem cells and cancer cells. I am curious about how the potency of differentiation is maintained in stem cells and what factors play major roles in particular cell lines. In order to fulfill this goal, quite a few technologies will be utilized such as SELEX-seq, ChIP-Seq, RNA-Seq, DNase I hypersensitivity assays and so on. With the help of these high throughput methods in the lab, I will study the interactions between transcription factors and the gene regulatory regions within the genome, trying to decipher the master transcription factors crucial for different cell fates. Furthermore, by looking through the results, we should understand the plasticity of the genome in the cells at a molecular level and finally we can obtain a clearer picture of the mechanisms of cell fate determination.

  • Grad student Jilin Zhang
Jilin

Gene expression is a complex dynamic process regulated by many distinct regulatory molecules, including DNA, RNA and proteins. To date, our understanding regarding the mechanism of gene regulation is limited due to insufficient knowledge of regulatory elements, even though sequencing technology has greatly broadened our horizons concerning the gene expression pattern alternation. My interest is to decipher the functional role of non-coding regions (or their products) in the gene regulation process, especially those regulatory elements associated with human diseases. To elucidate their roles may help to explain, at least partly, the mechanism by which gene expression is precisely controlled.

Lab Managers

  • PhD, Lab Technician Lijuan Hu
Lijuan

As one of the three lab managers, my responsibilities include running and maintaining two Illumina HiSeq 2000 next generation DNA sequencing instruments. I am also involved in high throughput siRNA screens of human cell cycle regulators, where we have targeted approx 23,000 human genes in order to find those that have an effect on the cell cycle. I also perform several other biology assays, for example cell culture, DNA- and protein purification, DNA- and protein gel analysis, PCR, qPCR and various DNA quantification techniques. The job also includes taking care of the day-to-day operation of the laboratory, such as ordering supplies and accepting shipments.

Karolinska High Throughput Center

  • PhD, Lab Manager KHTC Jianping Liu
Jianping

My job is to: 1) Oversee and manage the facility, equipment and diverse libraries at KHTC. 2) Attract screening project within and outside Karolinska Institute. 3) Provide guidance, training and expertise to the customers. 4) Help the director of KHTC with report writing and grant application. 5) Carry out high throughput siRNA/miRNA/small molecule screening to identify genes, microRNAs and chemical compounds which are linked to colorectal cancer.

Alumni

  • PhD Arttu Jolma
artto

Since completing his PhD in 2015, Arttu has moved to Hughes Lab at the University of Toronto, Canada.

Whilst in Taipale Group we developed a SELEX based assay for high throughput analysis of transcription factor binding specificities, which allowed efficient and economical generation of high quality models for these DNA-protein interactions. Our method utilized epitope tagged proteins to select their specific target sequences from partially randomized dsDNA sequences. We subsequently ran through extensive collections of full length TF and DNA binding domains that are mostly of mammalian origin, and  generated hundreds of binding specificity models. For further information see: “Multiplexed massively parallel SELEX for characterization of human transcription factor binding specificities” and “DNA-Binding Specificities of Human Transcription Factors“.

  • PhD Kazuhiro Nitta
Kazuhiro

Kazuhiro (Kaz) Nitta is a Japanese researcher with a background in animal development.

His main interests are involved with Gene transcription, namely how genes are regulated by each other and how these gene transcription machineries are conserved and diversified across species. In order to understand gene transcription, the characterization of up to a thousand transcription factors was necessary. By using our well established high throughput SELEX platform, Kaz determined the recognition sequence of transcription factors of human and fruit fly, Drosophila melanogaster, and evaluated to what extent they are conserved.

He has now joined the Transcriptome Technology Team in RIKEN, Japan.

  • PhD Jian Yan
Jian

After completing my five year graduate studies and a one year postdoc in Taipale lab focusing on deciphering the transcriptional regulation network, I started my visit to Prof. Bing Ren’s lab at Ludwig Institute for Cancer Research in San Diego, USA. With financial support from the International Postdoc Fellowship awarded by the Swedish Research Council, during my proposed three year visit my primary task will be to disclose the molecular determinants behind the organization of chromosome 3D structure.

The 3 Gb mammalian genome is highly compacted into chromosomes within a nucleus that is few microns in size. It has recently been found that the chromosome is subdivided into thousands of megabase sized topologically associating domains (TADs) which are highly conserved and play an important role in the regulation of gene expression. Some structural proteins, such as cohesin, CTCF and mediators have been associated with functions related to the maintenance of TAD structure. However, it remains unclear how these factors specifically implement their roles, whether/which other factors are also participating in waiving 3D chromosomes, and how the DNA sequence itself is regulating the domain structure. Understanding the hidden mechanisms would greatly advance our knowledge of gene regulation, which is the key question of many health problems such as diabetes, obesity and cancer.

  • PhD Fan Zhong
Fanzhong

After a 2 year scholarship in the Taipale Group, Fan Zhong has now returned to China and is an Associate Researcher in Bioinformatics at the Laboratory of Systems Biology, Institute of Biomedical Sciences, Fudan University.

High-throughput and high-dimensional Genome Wide Data (GWD) is an essential route for a more comprehensive and deeper understanding of the mechanisms underlying many biological processes. Next-Generation Sequencing (NGS) technology is a powerful tool to carry out nucleotide sequence based biological inquiries. As a bioinformatician, when I was in the Taipale Group I focused on integrating and mining NGS-centric GWD with other omics. My major interest is cell fate determination, which I approach by studying cancer related genes and their regulatory and encoding regions to discover the functional elements of these genes. I am also looking at how CpG methylation patterns affect these cancer related genes in tumor genesis (colorectal cancer), progression and metastasis and in normal cell cycle.

 

  • Post-doc Dr. Mikael Björklund

Regulation of cell growth in multicellular organisms. PI at College of Life Sciences, University of Dundee, Dundee

 Bjorklund Group

  • Post-doc Dr. Gonghong Wei

Regulatory Genomics and Functional Cancer Genetics. PI at Biocenter Oulu and Faculty of Biochemistry and Molecular Medicine, University of Oulu

http://www.oulu.fi/biocenter/groups/wei

  • Post-doc Dr. Anna Vähärautio

PI at University of Helsinki, Finland

  • Grad student Dr. Markku Varjosalo
Former Members

  • Lab Manager Sandra Augsten
Sandra

After 9 years in Sweden our family has now returned to Germany. We are starting our new life in Heidelberg and I started working as a Research Technician in Hennig Group at EMBL in January 2016.

In Taipale group, together with the other Lab Managers , I shared the responsibility for the organization of the sequencing unit. This job included the maintenance of two Illumina HiSeq 2000 next generation DNA sequencing instruments in addition to sequencing different libraries for our scientists and for KHTC customers. My job also included the day-to-day laboratory operations, performing various molecular biology assays and performing large-scale purification of recombinant proteins for different binding studies and X-ray crystallography.

 

  • PhD , Lab Manager KHTC Anders Eriksson
Anders

I joined the lab in Jan 2013 and worked at the Karolinska High Throughput Center (KHTC), which is located within the research division of Functional Genomics. KHTC is a core facility within Karolinska Institutet and affiliated with Science for Life Lab. It provides access for Swedish researchers to state-of-the-art and high-throughput equipment e.g. for the screening of large libraries of chemical compounds and siRNAs, in addition to instrumentation for next-generation sequencing. Whilst at KHTC, I  oversaw and managed the facility and was involved mainly in the planning phase and coordination of the various projects. Furthermore, I was responsible for the development of the facility, budget, grant applications and contact with researchers and potential customers at universities and other affiliations.

  • Lab Manager Anna Zetterlund
Anna-Zetterlund

As a lab manager in a molecular biology laboratory one of my responsibilities is to run and maintain two Illumina HiSeq 2000 next generation DNA sequencing instrument. I am also doing several molecular biology assays, e.g. protein purification, DNA- and protein gel analysis, PCR, qPCR and different DNA quantification techniques such as transformation and genotyping. The job also includes taking care of the day-to-day operation of the laboratory, like ordering supplies and accepting shipments.

  • Grad student Estefania Mondragon
Estefania

My research interest focuses on structural and functional aspects of ribonucleic acid (RNA). RNA is one of the three major biological macromolecules in the cell. Unlike deoxyribonucleic acid (DNA), well known for being the blueprint of the cell, RNA has a broader range of functions and structures.

As part of my doctoral thesis, I seek to understand how RNA molecules are recognized by proteins in order to explore the possibility of using RNA as a tool for artificial gene regulation. To accomplish this we are using an in vitro selection approach to find specific small RNA aptamers from a random library of RNAs that bind to the target protein with high affinity. This in vitro selection technique is called the systematic evolution of ligands by exponential enrichment (SELEX). As a PhD candidate in biomedical sciences at Mayo Graduate School, I have been collaborating with the Taipale lab since 2012. Through this collaboration we have adapted a standard multi-round RNA-SELEX protocol devised by the Maher lab to the High-Throughput technology of the Taipale lab. Our aim is to collect a large amount of data from the selected RNAs to understand sequence patterns and motifs that are recognized by DNA and RNA binding proteins. The information provided by these studies will allow us to better understand how proteins recognize nucleic acids. We believe that revealing these patterns will shed light into the possibility of making artificial RNA aptamer gene inhibitors and better prediction tools for RNA sequence specificity.

  • PhD, Research Engineer Natalia Nekhotiaeva
Natalia webpage

I am a highly experienced Senior Scientist with a proven track record of success leading and managing different projects within the Life Science sector with a focus on drug discovery. I have previous experience in academia and biotech industry designing and developing innovative biochemical and cell-based assays for high throughput screening, compound optimization and target validation. At KHTC I am responsible for HTS assays, assay development and optimization, and automation.

  • PhD Alexander Minidis
Alex

As a result of some of the mechanistic studies in Taipale Lab on tumor proliferation, we have a multitude of highly interesting oncogenes available. My aim is to perform small molecule based testing of these targets, which could potentially allow for the development of anti-cancer drugs.

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