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Genome, genome regulation and expression

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About this project

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In progress

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Jonas Halfvarson

Research Subject

In year 2006 I established the Swedish National Programme for genetics in IBD (SNP-IBD) in collaboration with Prof. Johan Söderholm, Linköping University, Prof. Tom Öresland, Sahlgrenska Academy and Associate Prof. Leif Törkvist, Karolinska Institute. Shortly thereafter Geneticists, Professor Mauro D´Amato, KI was attached to the group. Our research group has provided several genetic and functional studies of individual susceptibility genes. During recent years a tremendous progress has been made in the identification of genetic risk variants through genome-wide association studies (GWAs). Results from these studies have provided major insights into the pathogenic pathways of IBD and chronic intestinal inflammation, highlighting the importance of interaction between innate mucosal immunity and gut microbiota, activation of adaptive immunity, maintenance of gut epithelial barrier, as well as regulatory pathways such as autophagy. As a member of the management committee of the International IBD Genetic Consortium (IIBDGC), my group actively contribute to the collaborative efforts of the consortium.

 
Although there has been a great progress within in the field of genetics, the data has not gained any clinical benefit in daily clinical practice. Within the IIBDGC we are therefore trying to elucidate whether any loci can predict clinical outcome. Three pharmacogenomic pilot projects have recently been launched, where we are responsible for the project on response to infliximab.
In the last decade evidence has been accumulating that epigenetic modifications of DNA and histones can have a primary role in phenotypic outcomes, including human disease. To explore this we are collaborating with Professor Arturas Petronis, Toronto. We published (Nature Genetics 2009) a lower epigenetic concordance, based on DNA methylation, in dizygotic twin pairs than in monozygotic pairs, suggesting that the molecular mechanisms of heritability may not be limited to DNA sequence differences only. At present we are exploring the role of epigenetics in IBD.

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