Sleep controls hematopoiesis and regulates atherosclerosis: a novel neuro-immune axis

Humans spend one third of their life asleep. Despite its importance, we know surprisingly little about why we sleep and what impact it has on disease. Today, largely due to advances in electronic devices and instant communication systems, busy modern lifestyles promote work and social demands at the expense of rest and sleep. In this proposal we will study how sleep impacts the immune system and the risk of developing cardiovascular disease (CVD). Recent clinical studies have demonstrated that people with poor or insufficient sleep have a higher risk of CVD compared to those with a healthy sleep pattern. The reasons for this correlation have not been studied. We have established two innovative mouse models of sleep disruption. Our preliminary data suggest that sleep disruption activates the stem cells in the bone marrow that give rise to white blood cells. This results in an increase in the number of white blood cells in the sleep disturbed mice and an overall increase in inflammation. These white blood cells enter the walls of arteries which gives rise to fatty plaques, CVD and eventually heart attacks. We will study how sleep alters the biology of stem cells and white blood cells in detail. Using innovative mouse models and sophisticated genetic techniques we will track stem cell activation, function and movement. In addition, we will study how stem cells and white blood cells from sleep disturbed mice alter CVD progression and healing of the heart after a heart attack. This work will be conducted in collaboration with a team of renowned scientists and doctors at the Massachusetts General Hospital and Harvard Medical School. Our work will not only identify novel biological functions and new targets for CVD therapeutics but will also influence public policy. Governments and organizations can use our data as evidence to promote a healthy lifestyle that includes sufficient sleep.