Grant: Project Grant

Atherosclerosis, or hardening of the arteries, is a disease that is responsible for the majority of heart attacks and strokes. Understanding how the disease develops will give us insight into biochemical pathways that we can target in developing new treatments or drugs aimed at combatting this disease. Atherosclerosis involves the activation of the inflammatory system. Our objective is to understand how a key receptor molecule that coordinates metabolic and inflammatory responses of a variety of cells may be involved in atherosclerosis. That molecule is called interleukin-15 receptor alpha (IL-15RA). As part of this objective, we will perform proof of principle studies using genetically altered mice as a model system to test if IL-15RA might be a good target for combating atherosclerosis. We will also use genetic and molecular approaches to decipher how IL-15RA exerts its impacts on atherosclerosis development. Important preliminary evidence we have strongly suggests that IL15RA's influence driving atherosclerosis is separate from its protective role in inflammation. Understanding this separation will allow us to develop new drug candidates to selectively block IL15RA from driving atherosclerosis without interfering with its important role in protecting from infection. Development of such drugs will improve our tools to fight against atherosclerosis.