Midtveisevaluering - Eirik Tveit Solheim
Midtveisevaluering for ph.d.-graden ved Universitetet i Bergen for kandidat Eirik Tveit Solheim
Eirik Tveit Solheim er tilknyttet Klinisk institutt 1. Veiledere er Christian Vedeler og Cecilie Totland.
Characterizing the cerebellar degeneration-related proteins in cancer
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.