Genomics and Metagenomics in Inflammatory Disorders (Hov Group)

 

Johannes E.R. Hov
Group Leader

 

The projects in the genomics and metagenomics group aim to characterize and understand how alterations in the human genome and the gut microbial flora influence primary sclerosing cholangitis (PSC) susceptibility and cholangiocarcinoma development. We do this by applying modern genotyping and sequencing technologies in cross-sectional and interventional study designs.

Genetic factors are likely to play an important role in PSC development, as shown by an increased risk of disease in first degree relatives of patients with PSC. By studying disease genes and their function, the mechanisms by which PSC develop and eventually may be treated can be defined. Since many of the patients with PSC have concurrent inflammatory diseases (mainly inflammatory bowel disease, but also prototypical autoimmune diseases like type 1 diabetes and rheumatoid arthritis), these diseases are studied in parallel.

The gut microbiota is an important human organ comprising ten times more cells than the body itself, and likely plays a major role in human disease. Ongoing studies aim to characterize how the gut microbial community composition in patients with PSC interacts with immune regulation, bile acid metabolism and drugs. An important part of the activities is the standardization of methods related to key challenges in the field; study designs, sample collection and preparation, sequencing technology and bioinformatics. 

Lifetime risk of cancer of the bile ducts in patients with PSC is 10-20%. Few inflammatory conditions have an equally high risk of cancer development, and determining the genetic and epigenetic alterations responsible for this is of great importance. In addition to understanding the pathogenesis of cholangiocarcinoma, cancer genetics and epigenetics may serve as diagnostic and prognostic markers. 

Financial support and collaboration

The experimental projects are funded by the Norwegian PSC Research Center and the K.G. Jebsen Inflammatory Research Center (JIRC). Important collaborators include Andre Franke and John Baines (Christian-Albrechts university, Kiel), Rolf Berge (University of Bergen), Hanns-Ulrich Marschall (University of Gothenburg) and the inflammation groups at Research Institute of Internal Medicine at Oslo University Hospital (Pål Aukrust).

The research is performed in tight collaboration with the Norwegian PSC Research Center (NoPSC) 

 

Photo Øystein H. Horgmo, University of Oslo

From front and to the left: Silje Jørgensen, Johannes R. Hov, Cristiane Mayerhofer, Martin Kummen, Amandeep Kaur Dhillon, Gupta Udatha, Christopher Storm-Larsen, Kristian Holm and Liv Wenche Thorbjørnsen