Jussi Taipale, Ph.D., Principal Investigator

Herchel Smith Professor of Biochemistry, Distinguished Professor (Rådsprofessor from Vetenskapsrådet) of Medical Systems Biology, Professor and Vice-Director of the Finnish Center of Excellence in Tumor Genetics

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. He currently holds professorships at University of Cambridge (as Herchel Smith Professor of Biochemistry), Karolinska Institutet (supported by a Distinguished Professor grant from the Swedish Research Council) and University of Helsinki, where he is also the vice director of the Finnish Center of Excellence in Tumor Genetics.

The Taipale labs consist of two co-PIs (in KI and Helsinki), as well as senior scientists, postdoctoral fellows, graduate students and supporting staff in the form of lab managers and a personal assistant. The work of the group is supported by an advanced automated high throughput laboratory in Cambridge as well as sequencers and other equipment in all three locations.

 

 

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Senior Scientists

Inderpreet Sur, PhD, (Co-PI, KI)

Petros Papadopoulos, PhD, (Co-PI, Helsinki)

Ekaterina Morgunova, PhD

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.

 

 

Daniela Ungureanu, PhD, Docent

My research interests focus on the molecular mechanisms associated with kinases signaling. Protein kinases play a key regulatory role in nearly every aspect of cell biology making protein phosphorylation the most exploited form of posttranslational modification. Protein phosphorylation can modulate enzyme activity and it can also alter other biological activities such as transcription and translation. Kinases, as well as pseudokinases, are often dysregulated in a variety of diseases, especially cancer. Beyond the basic question of how kinases/pseudokinases function in normal and pathogenic conditions, there is also a significant interest in developing approaches to inhibit them. However, the expected development of drug resistance for the majority of kinase-specific inhibitors in the treatment of neoplastic disorders requires new approaches to solve this therapeutic challenge. My focus is toward understanding of drug-resistance mechanisms and the development of new technologies such as PROTAC-chimeras for the therapeutic targeting of kinases/pseudokinases in cancer.

 

Kimmo Palin, PhD

I am a senior staff scientist working in Taipale and Aaltonen groups at the University of Helsinki.
My research is Bioinformatics and Computational Biology from genetics and functional regulatory genomics perspective.
I’m involved especially with genetic epidemiology and biobank research related projects and have special interest in functional genomics, gene regulation and functional understanding of non-coding genetic variation.

 

Päivi Pihlajamaa, PhD

I am interested in the regulation of cellular processes by transcription factors, and especially, how aberrant transcriptional pathways promote tumorigenesis.

My main project focuses on studying the transcriptional targets of the MYC oncogene and their role in regulating cell growth and proliferation.To this end, I am using modern experimental methods in mammalian cells, such as CRISPR/Cas9-based precision genome editing and genome-wide screening approaches, to study the functional relationship between transcription factor binding, gene expression, and cell proliferation.

 

Connor Rogerson, PhD

I’m a cancer biologist with an interest in the underlying regulatory chromatin landscape of human cancer types. Cancer chromatin environments are now being identified as equally important (if not more) as cancer driver mutations. The culprits that construct these chromatin landscapes are cell-specific transcription factors that shape, rewire and activate chromatin. A small subset of transcription factors, known as pioneer factors, can bind closed chromatin to induce its activation. My research in the Taipale lab will focus on the role of these pioneer factors in cancer and how they contribute to cancer initiation and progression. 

 

 

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Postdoctoral fellows

 

Jiayin Hong, PhD

Chromatin architecture is complex, dynamic, and crucial for gene regulation. I have a keen interest in studying the general principles governing gene expression, specifically, how the linear genomic sequence is projected to 3D conformation in nuclear space, and how the 3D organization of chromosomes contributes to control of gene expression. I am using next generation sequencing to reveal the landscape of chromatin accessibility. Additionally, I have a broad interest in applying machine learning and data mining techniques to help understand how transcriptional regulatory elements such as promoters and enhancers coordinate and dictate gene expression, in the hope of learning the sequence-to-expression rules.

 

Shreya Saha, PhD

Gene expression is a complex phenomenon. The first step of gene expression involved binding transcription factors (TF) to the DNA element.Despite the discovery of many TFs, the determinants of TF binding and gene expression are still less understood. The binding of transcription factors involves many parameters, from small point mutations to significant structural changes.   I received my Ph.D. in November 2020 from the University of Helsinki. I joined the Taipale group as a postdoctoral research associate at the University of Cambridge in June 2021. I am interested to understand the binding specificities of TFs in free and nucleosomal DNA. Using different SELEX methods, I target to identify composite TF-TF motifs and understand the effect of CpG methylation and chromatin modification in TF binding. I am also interested in exploring the non-coding DNA elements that control differential gene expressions between healthy and cancer cells.  For this purpose, I aim to use the high throughput STARR -seq analysis and ATI assay facilities established in the Taipale group to fetch the active non-coding elements from random promoter libraries and cancer-specific promoter libraries. The broad moto of my research to understand gene expression in different cancer cells will potentially treat cancer and other multigenic disorders.

 

Tianyun Hou, PhD

I joined Taipale group as a Postdoctoral Research Associate in Cambridge on May 2021. My research interests are uncovering the regulatory mechanisms of gene expression by transcription factors (TFs), and systematically understanding how their dysregulation contributes to cancer development. To achieve these, I am using state-of-the-art techniques including CRISPR/Cas9 and CUT & RUN and high-throughput sequencing etc., to characterize the functional relationship between TFs, super-enhancers, epigenetics and cancer cells proliferation.  Based on this, it could help to identify potential factors conferring drug resistance and improving treatment sensitivity and even to screen novel therapeutic targets.

 

 Ilya Sokolov, PhD

I joined Jussi Taipale group in July 2021 as a postdoctoral researcher. My previous experience is rather diverse, combining experimental work in the field of cellular and molecular biology (including using animal models), and computational projects on developing artificial neural networks. The aim of my current projects is to solve global and fundamental “sequence-to-expression” problem by investigating novel transcription factors, analysing their interactions, and modifying standard SELEX protocol. In these studies, the key research approach comprises high-throughput experimental techniques followed by data analysis with the use of machine learning methods. This strategy allows fast screening, helps to achieve deeper understanding of the transcription mechanisms in general and to establish promising therapeutic targets.

 

Yujiao Wu, PhD

I am very interested in how the physical and chemical information written on DNA is accessed, selectively unfolded in different time and space and translated to be different ‘readable’ functional phenotypes which facilitate the so called ‘life’ to be life. My main project in Taipale Lab is to further develop the active TF identification (ATI) assay and apply this method in multiple diseases. Transcription factors (TFs) locate in the most inner layer of the transcription regulatory machineries and directly communicate with DNA, playing an essential role in gene regulatory network. ATI assay provides genome-wide measurement of all TF-binding activity in cell or tissue extracts. With this method, we can better understand the transcriptional regulatory landscape in certain physiological or pathological states and hopefully can have clues on how to rewrite the cell fate.

 

Rong Yu, PhD

I received my PhD in 2019 from Karolinska Institutet, and joined Taipale group in Stockholm in June 2021.Cancer causes the uncontrolled growth of abnormal cells and dynamic altering in the genome. Chemotherapy is the mainstay of treatment for numerous cancers. However, chemotherapeutic resistance occurs frequently and appears as a serious problem with most urgent challenge in the field of cancer. My research aim is to identify the regulatory processes that cause chemotherapy resistance of cancer cells and uncover potential novel biomarkers for clinical response. I am mapping the gene expression profile through a single-cell resolution to discover how different drug-responses are regulated by distinct clonal subpopulations within a tumor, thereby defining the alterations associated with drug-resistance.

 

Maria Osmala, PhD

I am a bioinformatician and computational biologist. I apply and develop computational, statistical and machine learning methods to understand biological phenomena. My research interests include multi-omics high-throughput sequence data analysis, epigenetics, functional genomics, system’s biology, non-coding regulatory elements, sequence determinants of regulatory elements, and cancer.

 

 

Tushar Warrier, PhD

A myriad of factors contribute to regulating the intricate processes of transcription and gene expression regulation. Therefore a detailed understanding of these complex factors and their interplay with their drivers and regulators can contribute to a comprehensive understanding of the molecular events that dictate each single cell’s fate and function.

I joined the Cambridge Taipale laboratory as a postdoctoral researcher in September 2022. I wish to delineate putative/consensus motifs for other classes of cellular determinants such as chromatin modifiers and histone modifiers, which are commonly indirectly associated with DNA through other factors, using the expertise of the Taipale lab in methods such as  CUT&RUN and SELEX. Additionally, I am piqued by the process of motif evolution and the contributions of viral elements of the genome to the same.  I would like to probe these questions and interface them with areas of my expertise such as epigenetics and genome topology to eventually develop translatable platforms for cell fate transformation, enhanced biomarker discovery and therapeutics, diagnostics.

 

Otto Kauko, MD, PhD

Growth signals are transmitted by diverse and redundant mechanisms. This redundancy is needed for tissue specific regulation of cell growth, but also makes it challenging to block growth signalling in cancer cells. 

Although signal transduction has been studied a lot, it is inadequately understood how the growth signal pathways interface with conserved processes of cell growth.

My aim is to identify and characterize common dependencies of proliferating cancer cells. To achieve this, I am manipulating proliferation and pathway usage in different cancer cell types, and collecting data using phosphoproteomics, thermal proteome profiling, single-cell RNAseq, and targeted genome editing based dropout screens.

 

Eevi Kaasinen, PhD, part time post-doc

My particular role in the Center of Excellence in Tumor genetics lies in processing and integration of DNA methylation, ChIP-seq, ATAC-seq, HiChIP and MNase-seq functional high-throughput sequencing data. I’m interested in deciphering epigenetic and chromatin alterations in diseases.

 

 

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PhD students

Tianyi Xiao

Gene expression is a complex process regulated in multiple levels. Histone modifications are post-translational modifications that occurs on histone tail proteins which change nucleosome stability, and thus regulate gene expression. 

I am interested in the relationships between transcription factors, histone modifications and chromatin accessibility. I am using SELEX and Cryo-EM to study the pattern of transcription factors’ interactions with histone modifying enzymes and nucleosomes.

 

Yinan Chen

The in vitro binding motifs of human transcription factors have been extensively analysed in recent years. However, how the higher-order chromatin architecture affects the binding pattern of transcription factors remains unclear. To tackle with this problem, we use SELEX approach to profile the binding landscape of transcription factors in the presence of various chromatin remodellers. These studies may extend our understanding of how the transcription factor binding dynamics contribute to gene transcription.

 

Yepeng Du

I am a PhD student working on molecular mechanisms associated with cancer development. Tumorigenesis  is associated with infinite cell division due to imbalance between proliferation and apoptosis, which is caused by transcriptional disorder. My interests is to use gene editing tool CRISPR/Cas9 to study the regulatory function of transcription factor Myc that modulates the expression of approximate 10% of all genes, especially those that are related to cell growth and proliferation.

 

 

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Lab managers

Margareta Kling Pilström, Stockholm

I joined the KI lab in February 2018, in time to move the lab into our current premises in Biomedicum in Solna.

Today I work with various molecular biology assays, including sample purification, gel analysis, PCR, immunohistochemistry etc. helping the researchers in the lab with various tasks.

I also take care of the day-to-day operation of the lab such as ordering of supplies, maintenance of instruments, handling inventories of instruments and chemicals etc., along with administrative tasks such as handling invoices and travels amongst other things.

 

 

 

 

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Administration

 

 

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Alumni

Former senior scientists and postdoctoral fellows

Gonghong Wei, PhD, Professor at Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, China

Emma Haapaniemi, PhD, PI Precision pediatrics and gene editing group,
Centre for Molecular Medicine, Norway.

Yimeng Yin, PhD, PI, School of Medicine at Tongji University, China

Anna Vähärautio, PhD, Academy Research Fellow, PI, University of Helsinki, Finland
Single-cell transcriptomics of cancer lab

Martin Enge, PhD, Assistant Professor at the Department of Oncology and Pathology at Karolinska Institutet and Karolinska universitetssjukhuset Solna, Sweden, https://ki.se/en/onkpat/research-team-martin-enge

Bernhard Schmierer, PhD, Director and Head of Facility, High Throughput Genome Engineering, Karolinska Genome Engineering, SciLifeLab, Dept. of Medical Biochemistry and Biophysics, Karolinska Institutet, Sweden

Biswajyoti Sahu, PhD, PI, Docent in Molecular Genetics, Applied Tumor Genomics Program, Research Programs Unit, Faculty of Medicine, University of Helsinki, Finland

Mikael Björklund, PhD, Associate Professor and Principal Investigator, Zhejiang University – University of Edinburgh Institute, China

Kazuhiro Nitta, PhD, Lecturer, Juntendo University, Graduate School of Medicine Diagnostics and Therapeutics of Intractable Diseases Intractable Disease Research, Japan

Song-Ping Li, PhD, Senior Researcher, Institute of Biomedicine, University of Turku, Finland

Sandeep Botla, PhD, Senior Scientist, Discovery Sciences, AstraZeneca, Sweden

Kashyap Dave, PhD, Senior Research Scientist at iCellate Medical AB,  Sweden

Fan Zhong, PhD, Associate Researcher in Bioinformatics at the Laboratory of Systems Biology, Institute of Biomedical Sciences, Fudan University, China

Ning (Nina) Wang, PhD, Tech Lead at Cepheid AB, Sweden

Alexander Minidis, PhD, Chemist and Project Leader at RISE Research Institutes of Sweden, Sweden

Fangjie Zhu, PhD, Professor at Haixia Institute of Science and Technology, Fujian Agriculture and Forestry University, China

Teemu Kivioja, PhD, University Researcher, Institute of Biotechnology, University of Helsinki, Finland

Minna Taipale, PhD, Senior Scientist, Cambridge Epigenetix, UK

Norman Zielke, PhD

Former graduate students

Tuomo Hartonen, Post-doctoral researcher at the Data Science and Genetic Epidemiology lab (https://www.dsgelab.org/), Institute for Molecular Medicine Finland.

Jilin Zhang, PhD, Assistant Professor at City University of Hong Kong https://www.cityu.edu.hk/bms/profile/jilinzhang.htm

Jian Yan, PhD, Assistant Professor at City University of Hong Kong https://www.cityu.edu.hk/bms/profile/jianyan.htm

Markku Varjosalo, PhD, PI Systems Biology/Pathology Research Group, University of Helsinki, Finland

Arttu Jolma Sidhu, PhD, Postdoc in the Laboratory of Timothy R. Hughes, University of Toronto, Toronto, Ontario, Canada.

Outi Hallikas, PhD, Post-doctoral fellow in Jukka Jernvall group at University of Helsinki, Finland

Mikko Turunen, PhD, Associate Research Scientist, Department of Systems Biology, Columbia University, USA

Bei Wei, PhD, Post-doctoral researcher in William Greenleaf lab, Stanford University, School of Medicine, USA

 

Former Karolinska High Throughput Center (KHTC) members

Anders Eriksson, PhD, Manager of Karolinska High Throughput Center.

Jianping Liu, PhD, Manager of Karolinska High Throughput Center.

Natalia Nekhotiaeva, PhD, Research Engineer of Karolinska High Throughput Center.

 

Former members

Biplu Prajapati, M.Sc., lab manager

Hyunju Park, former PA to professor Taipale

Katariina Sarin, lab manager

John Davies, PhD, lab manager

Jane Arnold, former PA to professor Taipale

Emma Inns, former PA to professor Taipale

Åsa Kolterud, PhD, Previously coordinated Syscol EU projects within the group. Currently Research coordinator with Prof Lauri Aaltonen at KI.

Sini Miettinen, B.Ls., lab manager

Sandra Augsten, lab manager

Maria Hoh, lab manager

Lijuan Hu, PhD, lab manager

Anna Zetterlund, lab manager

Estefania Mondragon, visiting graduate student