Grant: Fellowship: Canada Impact+ Research Training Awards - Postdoctoral

"Damage to blood vessels in the brain is a leading cause of memory loss and dementia, particularly vascular cognitive impairment. This condition develops when the brain receives insufficient blood over time, often due to plaque buildup and chronic inflammation in the vessels. Although these factors are well recognized, the mechanisms by which vascular dysfunction limit the brain’s capacity for repair remain unclear. This project aims to investigate the ubiquitin system, a natural cellular pathway that regulates protein activity. Functioning like the cell’s cleanup and recycling service, the ubiquitin system removes proteins that are damaged or no longer needed. When this system is impaired, harmful signals can accumulate, promoting chronic inflammation and structural changes in blood vessels. The research will focus on three genes – EIF2A, TGFBR1, and NFKBIA—which regulate inflammation, support vascular integrity, and facilitate communication between the circulation and the brain. The Rayner lab identified these genes with altered activity in the hippocampus and aorta of mice with atherosclerosis compared to healthy controls. Although each gene has been associated with vascular disease or dementia, their regulation by the ubiquitin system is poorly understood, and how they cooperatively mediate cardiac and brain disease development is not known. Molecular and functional studies will explore how disruptions in protein regulation compromise blood flow to the brain. By clarifying how impaired protein control drives long-term vascular damage, this research aims to identify new biological pathways involved in cognitive decline. These findings could support the development of strategies to protect brain blood vessels, preserve cognitive function, and reduce dementia risk."