Unravelling the Complex Epigenetics of Human T-cell Biology

DNA methylation is one of many epigenetic systems controlling gene expression in human cells.

A functioning DNA methylation system is essential for normal human development and is often disrupted in disease, especially cancer. DNA methylation involves the addition of a molecule, called a methyl group, to the DNA, which results in silencing of gene expression. Precisely how ‘painting’ with DNA methylation regulates gene expression patterns is still unclear. Even more unclear is how DNA methylation contributes to complex diseases, such as cancer, in which it is often disrupted. Understanding the function of DNA methylation in normal human biology, will allow us to understand its role in disease, with the ultimate goal of developing new drugs that target DNA methylation.

DNA methylation

My group studies DNA methylation mechanisms in CD4+ T-cells, a type of white blood cell that orchestrates the immune response to external threats such as bacteria and parasites and internal threats, such as cancer. In order to respond to such challenges CD4+ T-cells rapidly change into one of several different cell-types, each with specific but very different roles to play in the immune response. During this process, called differentiation, the CD4+ T-cells change the DNA methylation patterns across the entire genome. How T-cells achieve this feat is unclear, but it is key to their function.

 Lab work, DNA methylation

Using state of the art gene-editing approaches combined with genomics analysis we have begun to understand the function of DNA methylation in human T-cell biology. We then use this information to shed light on why DNA methylation is targeted for disruption in many cancers, focusing on the childhood cancer, T-cell acute lymphoblastic leukaemia (T-ALL).

Importantly, as many of the enzymes that control DNA methylation can be targeted with drugs and nutraceuticals (i.e. vitamin C), it is our ultimate aim to use our improved understanding of DNA methylation to guide the use of such compounds in the treatment of T-ALL and other malignancies.

Publications
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Selected publications

Colm Nestor, Raffaele Ottaviano, James Reddington, Duncan Sproul, Diana Reinhardt, Donncha Dunican, Elad Katz, J Michael Dixon, David J Harrison, Richard R Meehan (2012)

Genome Research , Vol.22 , s.467-477 Continue to DOI

Colm E Nestor, Raffaele Ottaviano, Diana Reinhardt, Hazel A Cruickshanks, Heidi K Mjoseng, Rhoanne C McPherson, Antonio Lentini, John P Thomson, Donncha S Dunican, Sari Pennings, Stephen M Anderton, Mikael Benson, Richard R Meehan (2015)

Genome Biology , Vol.16 , s.11- Continue to DOI

Colm Nestor, Antonio Lentini, Cathrine Hägg Nilsson, Danuta Gawel, Mika Gustafsson, Lina Mattson, Hui Wang, Olof Rundquist, Richard R. Meehan, Bernward Klocke, Martin Seifert, Stefanie M. Hauck, Helmut Laumen, Huan Zhang, Mikael Benson (2016)

Cell reports , Vol.16 , s.559-570 Continue to DOI

Publications in DiVA

2020

Danuta Gawel, Jordi Serra I Musach, Sandra Lilja, Jesper Aagesen, Alex Arenas, Bengt Asking, Malin Bengner, Janne Bjorkander, Sophie Biggs, Jan Ernerudh, Henrik Hjortswang, Jan-Erik Karlsson, Mattias Köpsen, Eun Jung Jung Lee, Antonio Lentini, Xinxiu Li, Mattias Magnusson, David Martinez, Andreas Matussek, Colm Nestor, Samuel Schäfer, Oliver Seifert, Ceylan Sonmez, Henrik Stjernman, Andreas Tjärnberg, Simon Wu, Karin Åkesson, Alex K. Shalek, Margaretha Stenmarker, Huan Zhang, Mika Gustafsson, Mikael Benson (2020) Correction: A validated single-cell-based strategy to identify diagnostic and therapeutic targets in complex diseases (vol 11, 47, 2019) Genome Medicine , Vol. 12 Continue to DOI

Research
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Flaw discovered in epigenetics research method

An error in one of the most widely used methods in epigenetics, DIP-seq, can cause misleading results, researchers at Linköping University, Sweden, have shown. This may have major significance in the research field, where “big data” and advanced methods of DNA analysis are used to study vast amounts of epigenetic data.

News and articles
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About me
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CV

  • 2016 Assistant Lecturer, Linköping University, Sweden
  • 2012 Post-doc, Linköping University, Sweden
  • 2008 Post-doc, University of Edinburgh, UK
  • 2003 Ph.D., University of Glasgow, UK
  • 2001 Bioinformatics Specialist, DeCODE Genetics Inc., Reykjavik, Iceland
  • 2001 Database developer, LION Biosciences GmbH, Cambridge, UK
  • 2000 Master of Bioinformatics, University of York, UK
  • 1999 Master of Computer Science, University of Cork, Ireland
  • 1995 B.A. Natural Sciences, Trinity College Dublin, Ireland

Network/assignment

  • Chair, Junior Faculty Club, Medical Faculty, Linköping University
  • Co-Chair, Centre for Personalised Medicine, Linköping University
  • Member, Academic Employment Board, Medical Faculty, Linköping University
  • Assistant Director, Department of Cell Biology, Linköping University

Program teaching activities

  • Medical Program
  • Masters in Experimental Biosciences
  • B.Sc. in Medical Bioscience
  • Ph.D. level courses

Organisation
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