Grant: Discovery Grants Program - Individual

The major goal of the research performed in my laboratory is to discover the mechanisms that control the process of blood vessel formation in skeletal muscle and fat tissues. Capillaries, the smallest type of blood vessel, distribute nutrients to all tissues in the body. All capillaries are composed of endothelial cells. These cells become activated by stimuli in the local environment to undergo the formation of new capillaries. Growth of new capillaries is a normal healthy response that enables our muscles and fat to adapt appropriately to varying energy demands, including the storage and use of dietary fats. To build a new capillary, endothelial cells must become activated and increase their numbers (proliferation), as well as to be motile (so they can form sprouts and move). Cells need a lot of energy and cellular supplies to support these functions, which they get by turning up a combination of possible metabolic pathways. However, there is much yet to learn about how this process is regulated. What are the factors that will determine how fast and effectively an endothelial cell reacts when it is stimulated to make a new blood vessel? I am particularly interested in variances between individuals based on sex and diet composition. The short-term goals of this research proposal are to define the influences of sex and sex hormones on endothelial cell metabolic processes and capacity to form new capillaries. We will examine the role of a regulator called ForkheadBoxO1, which we know is found in higher levels in female cells, as a mediator of differences between metabolism of female and male endothelial cells. We also will consider what happens to endothelial cells when they are exposed for a long time to a different type of nutrient as an energy source. How will they adapt to this alteration and will it affect their ability to form new blood vessels? A strength and uniqueness of this project is the combination of approaches that we will employ to examine sex differences in endothelial cells (both in mouse and cell culture models), which will allow us to uncover much information about the influence of sex and sex hormones on blood vessel growth. We will study the process of blood vessel growth in both skeletal muscle and fat tissues, so that we can gain valuable insight into potential differences in how endothelial cells behave in these two distinct tissues. Overall, this research will reveal sex and tissue distinct endothelial cell behaviours, which will build foundational knowledge of how blood vessel growth is controlled.