Digital Public Defence: Charlotte Larsen Ness
MD Charlotte Larsen Ness at Institute of Clinical Medicine will be defending the thesis Uveal Melanoma: Genetic and Epigenetic Characterisation for the degree of PhD (Philosophiae Doctor).
Photo: Harald Hjellum
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.
Due to copyright reasons, an electronic copy of the thesis must be ordered from the faculty. In order for the faculty to have time to process the order, it must be received by the faculty no later than 2 days prior to the public defence. Orders received later than 2 days before the defence will not be processed. Inquiries regarding the thesis after the public defence must be addressed to the candidate.
Digital Trial Lecture – time and place
- First opponent: Associate Research Fellow Sanna Barrand, Deakin University, Australia
- Second opponent: Professor Jørgen Krohn, University of Bergen
- Third member and chair of the evaluation committee: Professor II Eirik Helseth, University of Oslo
Chair of the Defence
Professor II Jon Berg-Johnsen, University of Oslo
Professor II Morten Carstens Moe, University of Oslo
Uveal melanoma (UM) is the most common primary intraocular tumour and has a high propensity for liver metastasis. The mechanisms that drive metastatic spread and drug resistance are largely unknown. The doctoral thesis consists of three separate papers investigating basic mechanisms in UM, thus outlining potential future treatment strategies.
The first paper sheds light on potential adaptive mechanisms in UM during cancer dissemination by exploring the effect of cell culture conditions (biopsies vs adherent cultures vs tumoursphere cultures) on gene expression. The tumoursphere cultures displayed traits associated with anoikis resistance, a shift towards a lipogenic profile and an upregulation of synovial sarcoma X breakpoint proteins (SSXs), known targets for immunotherapy in several cancers.
The second paper investigated differential DNA methylation in archived formalin-fixed paraffin-embedded UM specimens. DNA methylation profiling showed differential clustering of samples according to chromosome 3 status. Integrated differential DNA methylation and gene expression of two subsets of samples identified genes associated with early metastasis and poor prognosis.
The third paper investigated the expression of Connexin 43 (Cx43) in UM vs uveal melanocyte controls, and explored the effect of an Enhancer of Zeste homolog 2 (EZH2)-inhibitor on Cx43 expression. UM displayed decreased expression of Cx43. Furthermore, reduced membrane staining and diffuse cytoplasmic localisation of Cx43 were observed in UM. Inhibition of EZH2 in UM cell lines did not alter Cx43 expression, though a reduction of the histone modification H3K27me3 regardless of BRCA1- Associated Protein 1 (BAP1) status was evident.
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