The public defence will be held as a video conference over Zoom.
The defence will follow regular procedure as far as possible, hence it will be open to the public and the audience can ask ex auditorio questions when invited to do so.
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Digital Trial Lecture - time and place
Adjudication committee
- First opponent: Professor Allan Sirsjö, School of Medicine, Örebro University, Sweden
- Second opponent: Associate Professor Vivian de Waard, Amsterdam UMC, The Netherlands
- Third member and chair of the evaluation committee: Associate Professor Thomas Sæther, Institute of Basic Medical Sciences, University of Oslo
Chair of defence
Professor Marit Inngjerdingen, Institute of Clinical Medicine, University of Oslo
Principal Supervisor
Filip Segers
Summary
Cardiovascular diseases are one of the top causes of mortality worldwide, and the main underlying cause is atherosclerosis. Atherosclerosis is a multifactorial and progressive arterial disease where lipid accumulation and a low-level inflammatory response are at play. This leads to the formation of a plaque, which upon rupture can trigger thrombosis and artery occlusion, causing myocardial infarction or stroke.
Numerous studies have shown that cells within atherosclerotic plaques, like vascular smooth muscle cells (VSMCs), accumulate DNA damage. If left unrepaired, DNA damage can promote plaque instability leading to the fatal consequences of atherosclerosis. NEIL3 is a canonical DNA glycosylase involved in oxidative stress-damaged DNA base lesion repair, which seems to have functions beyond DNA repair, e.g., in cell proliferation. Yet, the role of NEIL3 in atherosclerosis is not well understood. The aim of this thesis was to examine the role of NEIL3 deficiency in atherosclerosis with a focus on VSMCs, using mouse- and cell-based models. Our results show that NEIL3 could be a new player in atherosclerosis affecting VSMC phenotypic identity.
Moreover, epitranscriptomics has emerged as a novel research field investigating the role of post-transcriptional RNA modifications on gene expression. Epitranscriptomics is previously shown to function in diseases like cancer, but a possible role in atherosclerosis is not known. The aim of this thesis was also to explore the role of RNA modifications in human atherosclerosis. Our results show that the well-studied RNA modification N6-methyladenosine is decreased in human atherosclerotic lesions, with dysregulated levels of several RNA modification enzymes.
Overall, this work intends to refine the understanding of the molecular mechanisms involved in atherosclerosis, where targeting NEIL3 or RNA modification-related proteins could help creating new prognosis tools and treatment strategies.
Additional information
contact the Research Support staff