Ivan Radovanovic, MD, PhD

Brain arteriovenous malformations (BAVMs) are a tangle of large, abnormal blood vessels within the brain. The resulting high blood flow can cause these blood vessel malformations to rupture and bleed, which may lead to severe illness or even death. BAVMs are a leading cause of bleeding in the brains of children and young adults. We have identified spontaneous, non-inherited genetic mutations in a gene called KRAS in the majority of BAVM patients. These mutations occur in the cells that line blood vessels within BAVMs, but do not occur elsewhere in the patient. The KRAS gene codes for a protein that serves as an ON-OFF switch in blood vessel cells. When the KRAS gene is mutated, blood vessel cells are stuck in the ‘ON’ state and think that they are receiving cell growth and migration signals, even when they are not. Our research further aims to identify the defective genes in BAVMs that do not have mutations in KRAS, and to understand how KRAS mutations influence the formation of BAVMs. We also extensively study different vascular cell populations in BAVMs, in brain tumours as well as in normal adult and developing brains to understand how the normal vasculature is formed in the brain during development and how it fails in vascular malformations of the brain and other pathologies that depend on abnormal vasculature such as brain tumours. To do this we use advanced genomic and sequencing techniques that can sequence the genome and the genes expressed in single cells.

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Associate Professor, Department of Surgery, University of Toronto
Staff Neurosurgeon, Toronto Western Hospital, UHN