The prevalence of cardiovascular disease continues to increase, despite the addition of nearly 30 FDA-approved drugs with cardiovascular disease indications since 2010. In 2015 deaths from cardiovascular disease topped 17 million and totaled more than $316 billion in healthcare costs and lost productivity. By 2030, more than 23 million deaths annually are predicted. Besides modifiable lifestyle factors, the mainstay of pharmacotherapy for cardiovascular disease is lipid-lowering agents. Wnt signaling has been shown to be important in the pathogenesis of cardiovascular disease, yet NO THERAPY targeting this pathway currently exists. We have data showing that small molecule Wnt inhibition can substantially improve cardiovascular disease, specifically atherosclerosis through lipid-lowering effects as well as through mitigation of inflammatory cytokines and restoration of endothelial cell fuel preference defects, which represent 2 novel mechanistic approaches. With a patent in hand that allows for the use of Wnt inhbitiors as a novel therapy for cardiovascular disease, my goal is to develop new molecules which would represent a first-in-class therapuetic approach to the leading cause of mortality worldwide.