Our research focuses on understanding the biological processes that lead to abnormal usage of genetic information in disease, in particular via so-called 'epigenetic' mechanisms. Epigenetic means a modification of the DNA and associated chromatin that changes the expression pattern of genes without changing the DNA sequence of the genes. DNA methylation of cytosine residues at CpG dinucleotides is one example of epigenetic gene regulation. In addition, the packaging of the DNA into regions of active and silent chromatin is another example. These mechanisms are often deregulated in cancer leading to over-expression or silencing of critical genes. But also in many other diseases it has now become apparent that both genetic and epigenetic events are responsible for the observed phenotype.
Our area of interest can be divided into three main topics:
- Understanding epigenetic mechanisms and their deregulation in diseases.
- The interplay between genetics and epigenetics.
- The development of novel assays for epigenetic testing.
One of the ongoing projects in the group concerns epigenetic changes in prostate cancer where we identified that such changes can encompass large chromosomal regions resulting in silencing of many neighbouring genes ("Long Range Epigenetic Silencing" or LRES). Current work focuses around a further understanding of the underlying mechanism(s).
Marcel Coolen is leader of the workgroup Human Epigenetics, which is embedded within the Department of Human Genetics. With his team, he dissects epigenetic networks and mechanisms underlying human function and disease.
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