Grant: CIHR Fellowship

Atherosclerosis is a chronic inflammatory disease characterized by the progressive buildup of plaques inside arteries. As these plaques rupture or erode, they can lead to heart attack and stroke. It is now known that a group of white blood cells, called monocytes, can worsen atherosclerosis if their recruitment from the bone marrow to the plaques is increased. Specifically, these monocytes are developed from blood stem cells in the bone marrow, and their increased production can enhance their exit from the bone marrow and traffic to the plaques. Therefore, my research focuses on determining the factors that increase monocyte production from blood stem cells. Recently, our group has shown that in atherosclerosis, a specific resident cell type in the bone marrow, called endothelial cells, increased the secretion of a factor that stimulated an excessive production of monocytes. However, it remains unclear if other resident cell types in the bone marrow also participate in this process. Therefore, in this study, I propose to analyze all resident cell types in the bone marrow with unbiased profiling, expecting to identify all cells that regulate monocyte production, and their altered functions, by the end of the study. To ensure my findings are physiologically relevant, I will analyze the bone marrow from mice and humans with atherosclerosis, comparing to controls without atherosclerosis. Overall, this is an important endeavor because after identifying the cells responsible for inducing monocyte overproduction, I can selectively silence their harmful activities by using a tool that our lab has developed, thus curbing atherosclerosis progression. To date, Health Canada has listed that atherosclerosis is the second leading cause of death in Canada. This reflects the urgency of developing novel effective therapeutics against atherosclerosis, and my proposed study has the translational potential to improve the overall well-being of Canadians diagnosed with atherosclerosis.