Defence: Tor Espen Stav-Noraas
MSc Tor Espen Stav-Noraas at Institute of Clinical Medicine will be defending the thesis "Interleukin-33 and Notch signaling in antiviral defense and inflammation" for the degree of PhD.
Foto: Hanne Kathrine Stav-Noraas
Trial Lecture - time and place
See Trial Lecture.
- 1st opponent: Professor Daniel Pinschewer, University of Basel
- 2nd opponent: Resident dermatologist/Senior researcher Øystein Sandanger, Oslo University Hospital
- Committee Chair: Adjunct Professor Tom Eirik Mollnes, University of Oslo
Chair of the Defence
Professor Svein Olav Kolset
Group Leader Guttorm Haraldsen
An extensive network of blood vessels in the human body is formed by endothelial cells. These cells are central players in early defense against pathogenic bacteria, viruses or parasites, and they are involved in recruitment of leukocytes. Endothelial cells are activated in response to pathogens, damage or by inflammatory signals, leading to an inflammatory response. In this context, the inflammatory cytokine interleukin-33 (IL-33) is widely expressed by endothelial cells and acts as an activator of lymphocytes in response to viral infections. Furthermore, cell-to cell Notch signaling modulates the response of the endothelial cells by regulating IL-33 expression and inflammatory target genes.
The doctoral work focused on studying the interplay between endothelial cells, inflammation and viruses in the context of IL-33 and Notch signaling.
First, we investigated the response of endothelial cells after recognizing non-replicative adenovirus. Endothelial cell DNA damage sensors (associated with repair of double stranded DNA) recognized adenovirus, leading to increased expression of IL-33. Second, infection with the replicative (wild type) version of adenovirus prevented expression of IL-33, implying a functional role of IL-33 in an anti-viral response that is counteracted by the wild type virus. To this end, reducing endothelial IL-33 partially prevented activation of the DNA damage machinery. Finally, endothelial Notch signaling promoted inflammation in a mouse model. We made this conclusion based on our demonstration that endothelial Notch signaling promotes inflammation by facilitating Histone 3 acetylation of lysine 27 (H3K27ac) of a unique set of inflammatory enhancer regions.
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