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Midway evaluation

Midway evaluation - Eirik Tveit Solheim

Midway evaluation for the PhD degree at the University of Bergen for candidate Eirik Tveit Solheim

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Eirik Tveit Solheim is affiliated with the Department of Clinical Medicine. Supervisors are Christian Vedeler and Cecilie Totland.

Project

Characterizing the cerebellar degeneration-related proteins in cancer

Abstract

Paraneoplastic cerebellar degeneration (PCD) is a rare, autoimmune disease in which ectopic tumour expression of neural proteins triggers an autoimmune response targeting both cancer cells and the neurons endogenously expressing these proteins, causing neurodegeneration. PCD is characterized by severe pancerebellar dysfunction, which presents clinically with truncal ataxia, nystagmus, vertigo, dysarthria and diplopia. PCD is often seen in association with anti-Yo antibodies in a small subgroup of women with breast or ovarian cancer. Anti-Yo antibodies recognize three proteins expressed by Purkinje cells in the cerebellum called cerebellar degeneration related proteins, namely CDR1, CDR2, and CDR2L. These proteins are also expressed by the cancer, but the functional consequence of this is unknown.

This PhD project aims to characterize the CDR proteins in cancer. Using knockout cells and a multi-omics approach, novel pathways and molecular processes impacted by the CDR proteins in ovarian cancer have been identified.

CDR1 antisense RNA has been shown to be differentially expressed in ovarian tumors. The project explores whether this differential expression is reflected in the serum exosomes of the patients, and the potential value of using exosomal RNA as a novel biomarker in ovarian cancer and PCD.