Midtveisevaluering - Titas Gladkauskas
Midtveisevaluering for ph.d.-graden ved Universitetet i Bergen for kandidat Titas Gladkauskas
Titas Gladkauskas er tilknyttet Klinisk institutt 1. Veiledere er Cecilie Bredrup og Eyvind Rødahl.
Disease-causing mechanisms and precision treatment of patients with mutations in PDGFRB
Platelet-derived growth factor receptor β (PDGFRB) is a cell-surface receptor tyrosine kinase that plays an essential role in cell proliferation, survival, differentiation, and blood vessel development. Several gain-of-function PDGFRB variants causing ligand-independent activation of the kinase have been reported. Such activation causes distinct conditions: Kosaki overgrowth syndrome, Infantile myofibromatosis, Penttinen syndrome, and Ocular Pterygium-Digital Keloid Dysplasia (OPDKD). Our research group focuses on hereditary forms of corneal vascularization and has identified several PDGFRB variants resulting in blindness early in life due to corneal overgrowth. Why and how these PDGFRB variants result in different clinical conditions and why the cornea is often involved remained to be explored. Studying these PDGFRB variants could offer insights into corneal vascularization in general and enable personalized treatment with tyrosine kinase inhibitors (TKI) for these patients.
The aim of this Ph.D. project is to describe the molecular consequences of these variants and also a novel PDGFRB variant causing blindness in childhood due to aggressive corneal vascularization. Particular focus has been on examining various corneal environmental factors and on identifying drugs that could be used in personalized medicine to treat these patients.