Karl Ekwall

Karl Ekwall

Professor
Telephone: +46852481039
Visiting address: Blickagången 16, 14151 Flemingsberg
Postal address: H7 Medicin, Huddinge, H7 GUT Ekwall, 171 77 Stockholm
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About me

  • Karl Ekwall is an expert on genetics, chromatin and epigenomic analyses, using primarily fission yeast (S. pombe) as a model organism. During his PhD at Uppsala university he performed pioneering genetic screens for position-effect variegation in S. pombe. As a post-doc in R. Allshire’s group at MRC Human Genetics (Edinburgh) he identified the Swi6 (HP1) protein as the first centromeric chromatin protein to be described in fission yeast (Ekwall et al Science, 1995). He also demonstrated that the control of epigenetic states at centromeres was governed by histone acetylation (Ekwall et al Cell, 1997).

    After starting his own laboratory at Karolinska Institute in 1999 Ekwall has made important contributions towards understanding the role of RNAi in heterochromatin assembly (PNAS, 2002; Genes & Dev, 2005). In fact, the ensemble of research on epigenetic regulation of centromeric heterochromatin has provided a universal paradigm for unraveling the chromosomal regulatory machinery that operates at the chromatin level to control gene expression (Ann. Rev. Genetics, 2007). Thus, Ekwall has since then taken a holistic approach towards understanding epigenetic regulation, unraveling mechanisms at work both in centromere and gene regulation. One such mechanism is histone deacetylation by HDAC enzymes. Ekwall developed a robust epigenomic methodology for S. pombe after a sabbatical in M. Grunstein’s laboratory at UCLA and used this for systematic study of the specificity and functions of HDACs (EMBO J 2005; EMBO J 2007). His team has determined the mechanistic in vivo and in vitro functions for Chd1 in nucleosome disassembly and spacing (EMBO J 2007; 2012). Chd1 is a key chromatin remodeler, recently implicated in mouse stem cell maintenance and control of pluripotency. The Ekwall group provided evidence for DNA topoisomerases and histone ubiquitination in chromatin regulation (EMBO J 2010; PloS Genetics 2013; Nature Struct Mol Biol 2010, 2014). Ekwall also developed clinical aspects of his research. He founded the Swedish Epigenetics network (2007) bridging basic and clinical research in epigenetics in Sweden. Ekwall’s group has investigated epigenetic control of human blood cell differentiation (Blood 2014; Nature 2014) and epigenetic changes in leukemia in collaboration with clinical research groups at KI (Blood 2010, 2014; Leukemia 2013).

Research

  • My group is carrying out both basic research in epigenetics and applied research in cancer epigenetics. We are studying yeast cells (S. pombe) and human cell lines for the basic research and we are using human blood cells as a model to study cell differentiation and cancer. Our current research is focused on characterizing the function of chromatin remodeling factors and histone modifications during cellular quiescence.

Articles

All other publications

Grants

  • Swedish Research Council
    1 January 2022 - 31 December 2024
  • Swedish Research Council
    1 January 2019 - 31 December 2021
  • Epigenetics, chromatin transformation and cancer
    Swedish Cancer Society
    1 January 2018
    Epigenetic regulation is based on various types of modifications of the genome (chromatin) that are needed for the same DNA sequence to be read in different ways in the> 250 different cell types that exist and this is a prerequisite for normal development and the body's function. The human 'epigenom' is a map of all these modifications and the map looks different depending on which cell type and tissue it comes from. A relatively newly discovered form of epigenetic regulation called 'nucleosome remodeling' is involved in this regulation that is done using SWI2 / SNF2 'chromatin transformation enzymes'. SWI2 / SNF2 enzymes are of central importance for epigenetic regulation and can thus control the epigenetic states of the cells by influencing the positions of the 'nucleosomes'. Nucleosomes are the cylindrical protein / DNA structures that pack the DNA into the chromosomes and which simultaneously carry the majority of the epigenetic modifications. The chromatin converting enzymes can turn off and turn on gene expression by moving on nucleosomes and thereby making the DNA sequence available for reading via transcription factors and RNA polymerase. The clinical benefit of the project is partly an increased basic understanding of epigenetic regulation with regard to the function of certain chromatin converting enzymes and the protein complex Paf1. This is a knowledge base that can be used to understand the mechanism of diseases with altered epigenetic states. In the longer term, these studies can lead to improved diagnostics, prognosis and treatment based on epigenetic mechanisms. The work on inhibitors directed against chromatin transformation enzymes can directly lead to new epigenetic treatments, for example in leukemia and prostate cancer.
  • Chromatin transformation enzymes, cell differentiation and new strategies for epigenetic cancer treatment
    Swedish Cancer Society
    1 January 2017
    All human cells contain the same DNA sequence. Despite this, the DNA sequence can be used in different ways in the> 250 different cell types that exist and this is a prerequisite for normal development and the body's function. Epigenetic regulation is based on various types of modifications of the genome (chromatin) that are needed for the DNA sequence to be read correctly. The human "epigenom" is a map of all these modifications and the map looks different depending on which cell type and tissue it comes from. One important question is how an epigenetic condition can change as cells differentiate (mature). A relatively newly discovered form of epigenetic regulation called "nucleosome remodeling" is involved in this regulation that is done with the help of "chrominoma conversion enzymes". These SWI2 / SNF2 enzymes are of central importance for epigenetic regulation and can thus control the epigenetic states of the cells by influencing the positions of the nucleosomes. Nucleosomes are the cylindrical protein / DNA structures in which the DNA is packaged in the chromosomes and which at the same time carries the majority of the epigenetic modifications. The chromatin converting enzymes can turn off and turn on gene expression by making the DNA sequence available for reading. We want to understand the role of the SWI2 / SNF2 enzymes in epigenetically programming the cells during differentiation. The work is important to understand the background to acute myeloid leukemia (AML). AML is caused by an epigenetic error programming where the SWI2 / SNF2 enzymes play an important role. In the slightly longer term, the work can give new hope for better diagnosis and treatment of acute myeloid leukemia and other blood disorders with epigenetic interference. We are also looking for new future drugs that can inhibit the activity of SWI2 / SNF2 enzymes. Our goal is to find new strategies for epigenetic cancer treatment.
  • Swedish Research Council
    1 January 2017 - 31 December 2018
  • Chromatin transformation enzymes, cell differentiation and new strategies for epigenetic cancer treatment
    Swedish Cancer Society
    1 January 2016
    All human cells contain the same DNA sequence. Despite this, the DNA sequence can be used in different ways in the> 250 different cell types that exist and this is a prerequisite for normal development and the body's function. Epigenetic regulation is based on various types of modifications of the genome (chromatin) that are needed for the DNA sequence to be read correctly. The human "epigenom" is a map of all these modifications and the map looks different depending on which cell type and tissue it comes from. One important question is how an epigenetic condition can change as cells differentiate (mature). A relatively newly discovered form of epigenetic regulation called "nucleosome remodeling" is involved in this regulation that is done with the help of "chrominoma conversion enzymes". These SWI2 / SNF2 enzymes are of central importance for epigenetic regulation and can thus control the epigenetic states of the cells by influencing the positions of the nucleosomes. Nucleosomes are the cylindrical protein / DNA structures in which the DNA is packaged in the chromosomes and which at the same time carries the majority of the epigenetic modifications. The chromatin converting enzymes can turn off and turn on gene expression by making the DNA sequence available for reading. We want to understand the role of the SWI2 / SNF2 enzymes in epigenetically programming the cells during differentiation. The work is important to understand the background to acute myeloid leukemia (AML). AML is caused by an epigenetic error programming where the SWI2 / SNF2 enzymes play an important role. In the slightly longer term, the work can give new hope for better diagnosis and treatment of acute myeloid leukemia and other blood disorders with epigenetic interference. We are also looking for new future drugs that can inhibit the activity of SWI2 / SNF2 enzymes. Our goal is to find new strategies for epigenetic cancer treatment.
  • Chromatin transformation enzymes, cell differentiation and new strategies for epigenetic cancer treatment
    Swedish Cancer Society
    1 January 2015
    All human cells contain the same DNA sequence. Despite this, the DNA sequence can be used in different ways in the> 250 different cell types that exist and this is a prerequisite for normal development and the body's function. Epigenetic regulation is based on various types of modifications of the genome (chromatin) that are needed for the DNA sequence to be read correctly. The human "epigenom" is a map of all these modifications and the map looks different depending on which cell type and tissue it comes from. One important question is how an epigenetic condition can change as cells differentiate (mature). A relatively newly discovered form of epigenetic regulation called "nucleosome remodeling" is involved in this regulation that is done with the help of "chrominoma conversion enzymes". These SWI2 / SNF2 enzymes are of central importance for epigenetic regulation and can thus control the epigenetic states of the cells by influencing the positions of the nucleosomes. Nucleosomes are the cylindrical protein / DNA structures in which the DNA is packaged in the chromosomes and which at the same time carries the majority of the epigenetic modifications. The chromatin converting enzymes can turn off and turn on gene expression by making the DNA sequence available for reading. We want to understand the role of the SWI2 / SNF2 enzymes in epigenetically programming the cells during differentiation. The work is important to understand the background to acute myeloid leukemia (AML). AML is caused by an epigenetic error programming where the SWI2 / SNF2 enzymes play an important role. In the slightly longer term, the work can give new hope for better diagnosis and treatment of acute myeloid leukemia and other blood disorders with epigenetic interference. We are also looking for new future drugs that can inhibit the activity of SWI2 / SNF2 enzymes. Our goal is to find new strategies for epigenetic cancer treatment.
  • Swedish Research Council
    1 January 2015 - 31 December 2018
  • 'SNF2' chromatin transformation enzymes and cell differentiation
    Swedish Cancer Society
    1 January 2014
    Epigenetics was introduced as a theory in developmental biology in the 1970s and has evolved into a hot molecular biology research area. Epigenetics is about the hereditary properties of the cells that can be altered without changing the genetic information (the DNA sequence). Epigenetic regulation is based on various types of modifications of the genome (chromatin). So-called "nucleosomes" can be modified epigenetically. Nucleosomes are the cylindrical protein / DNA structures in which the DNA is packaged in the chromosomes. A newly discovered and exciting epigenetic regulation is called 'nucleosome remodeling' and is done using 'SNF2' enzymes. The project has two parts. In the first, we study so-called "SNF2" chromatin transformation enzymes in a model system to define their different basic functional mechanisms which are not yet known in detail. In man, there are no less than 53 different SNF2 chromatin converting enzymes and because of this great complexity we use a simpler cellular model system. Fission yeast has only 20 different SNF2 enzymes, which means that we can systematically study these with "genomic-wide" methodology. In the second part of the project, we study human SNF2 enzymes and, in particular, those involved in blood cell formation (hematopoiesis). To create a knowledge base regarding the function of SNF2 enzymes. To develop cancer epigenetics as a new area of research. To map the role of SNF2 enzymes in normal blood cell formation in humans. The goal is to understand their role in epigenetically programming the cells as they mature (differentiate). This work is important in understanding the background to acute myeloid leukemia (AML). AML is caused by an epigenetic error programming where the SNF2 enzymes play an important role. In the slightly longer term, the work can give new hope for better diagnosis and treatment of acute myeloid leukemia and other blood disorders with epigenetic interference.
  • Swedish Research Council
    1 January 2014 - 31 December 2016
  • Knut and Alice Wallenberg Foundation
    1 January 2011 - 1 January 2016
  • Swedish Research Council
    1 January 2011 - 31 December 2014

Employments

  • Professor, Department of Medicine, Huddinge, Karolinska Institutet, 2024-

Degrees and Education

  • Professor-competent in Molecular Biology, Södertörn University, 2007
  • Docent, Karolinska Institutet, 1999
  • Doctor of Philosophy (Molecular Biology), Uppsala University, 1994
  • Bachelor of Microbiology, Microbiology, Uppsala University, 1988

Distinction and awards

  • The Göran Gustafsson Prize in Molecular Biology, Göran Gustafsson Foundation, 2009
  • Royal Swedish Academy of Sciences (KVA) Research Fellow, Royal Swedish Academy of Sciences, 2007
  • Associate Professor, Södertörn University, 2000
  • Appointed as Assistant Professor (Swedish Medical Research Council position ‘MFR’), Karolinska Institutet, 1997

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