Vincent Dion, SNF Professor

Vincent Dion started his scientific career in 1999 as a summer student in Stanley L. Miller’s laboratory at UCSD (USA). He also spent time as an undergraduate in the laboratory of David H. Evans at the University of Guelph (Canada), where he got a B.Sc. with honours in 2002. In 2007, he obtained his PhD from Baylor College of Medicine (USA), under the supervision of John H. Wilson, for defining the role of DNMT1, a DNA methyltransferase, in preventing disease-causing CAG/CTG repeat expansions. As a postdoc with Susan M. Gasser at the Friedrich Miescher Institute (Switzerland), he discovered a novel role for chromatin remodeling enzymes in the repair of deleterious DNA double-strand breaks. He joined the CIG in 2013 as an assistant professor with the support of a professorship from the Swiss National Science Foundation. Since then, his lab has made key contributions towards the development of gene editing approaches to correct mutations that cause 14 different neurological, neuromuscular, and neurodegenerative diseases, which all remain without a cure. 

Keywords: DNA repair, chromatin, genome stability, neurodegenerative diseases, nuclear organization.

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Research summary

Because we breathe oxygen and that most of our body is made of water, our DNA is being damaged at a rate of about 100 000 lesions per cell per day. This enormous amount of damage must be repaired efficiently and accurately if the genetic information contained in the genome is to be maintained. This fundamental process of DNA repair is the focus of the laboratory.

Mutations in several DNA repair genes greatly increase cancer predisposition and the malfunction of several caretakers of the genome lead to neurological disorders (1). These observations highlight the importance of maintaining genome stability for human health.

Each and every cell in our body contains 2 meters worth of DNA that needs to be packaged into a nucleus of about 20 to 50 micron in diameter. To put this in perspective, a micron is 1/1’000’000 of a meter and a human hair is about 100 microns wide. To achieve this packaging, DNA is wrapped around histone octamers to form nucleosomes and higher-order chromatin structures. Chromatin therefore helps to package the genome. Additionally, it provides great opportunities for the regulation of DNA-based events since nucleosomes can mask the binding site of many DNA binding proteins. This interplay between chromatin structure and DNA metabolism has been extensively studied in the context of transcription, but much less is known about its impact on DNA repair.


To study how chromatin affects DNA repair events, our laboratory focuses on tandem repeats composed of pure stretches of CAG or CTG trinucleotides. These loci are hotspots for genome instability and the size of the repeat can expand greatly, in some cases reaching thousands of trinucleotides at a single locus. The instability depends primarily on the normal activity of DNA repair on an unusual DNA sequence. As the repeat tract gets longer, it becomes more unstable and adopts chromatin configurations that bear many of the hallmarks of dense heterochromatin (2). These characteristics make trinucleotide repeats an ideal paradigm to explore the relationship between genome stability and chromatin structure at endogenous loci. We use a combination of cutting-edge molecular biology, genetics, and genomics in human cells, including patient-derived induced pluripotent stem cells, to identify new players in trinucleotide repeat instability and to study the effects of chromatin structure and organization on DNA repair. Specifically, we have projects asking the following questions:

  1. Do chromatin modifiers affect repeat instability directly by changing the local structure of the expanded repeat tract? Many chromatin modifying enzymes have been implicated in repeat instability but their exact role is unclear. This is because every study conducted so far includes loss of function experiments that do not permit the differentiation a local effect on chromatin structure or indirect causes, such as changes in transcription genome-wide. Here we have designed novel molecular assays to address the roles of chromatin modifying enzymes in repeat instability.
  2. What is the impact of nuclear organization on trinucleotide repeat instability? Here we aim to determine whether expanded trinucleotide repeats impact their 3D organization in the nucleus and whether this organization in turn influences their repair and thus their instability.
  3. Can we induce CAG repeat contractions without also inducing expansions? This project is especially relevant to human health. Indeed, the expansion of trinucleotide repeats cause a number of neurological and neuromuscular disorders, including Huntington disease, myotonic dystrophy, as well as several spinocerebellar ataxias. All of these disorders remain without a cure. Inducing contractions would, in theory, remove the underlying cause of the disease and provide a therapeutic avenue. This project is focused on finding conditions or treatments that specifically contract the repeat tracts and that would therefore alleviate the molecular symptoms. We have recently shown (3) that the CRISPR-Cas9 nickase can be targeted to the expanded repeat tract and induces almost exclusively contractions (Fig. 1), which is an exciting first step towards the development of gene editing approaches for therapeutic purposes.


A long-term goal of our research is to understand the mechanism of trinucleotide repeat instability to such an extent that we can manipulate it at will and induce repeat contractions in patients. We are especially interested in being able to manipulate local chromatin structure to change the bias in repeat expansion usually seen in human patients.


  1. Dion, V. (2014) Tissue specificity in DNA repair: lessons from trinucleotide repeat instability. Trends Genet, 30, 220-229.
  2. Dion, V. and Wilson, J.H. (2009) Instability and chromatin structure of expanded trinucleotide repeats. Trends Genet, 25, 288-297.
  3. Cinesi, C., Aeschbach, L., Yang, B. and Dion, V. (2016) Contracting CAG/CTG repeats using the CRISPR-Cas9 nickase. Nat Commun, 7, 13272.

For a full list of publications, see the ‘publications’ section of this webpage

Public Outreach

Dec 2017

Interview (The ALS Research Forum) about using CRISPR-Cas9 to treat neurological diseases (in English).

Sept 2017

Newspaper interview (Allez-Savoir) interview about CRISPR-Cas9 (in French).

June 2017

Radio interview (RTS – la première) for the CQFD program as part of a 1hr special on CRISPR-Cas9 (in French).

Nov 2016

Radio interview (RTS- la première) for the CQFD program on how to use CRISPR to treat expanded trinucleotide repeat diseases (in French).


Twitter: @VDion_and_Lab



Vincent Dion

Tel: +41 21 692 3901


Administrative assistant

Nathalie Clerc
Tel: +41 21 692 3920

Génopode - CH-1015 Lausanne
Tel. +41 21 692 22 00
Fax +41 21 692 22 11