Malhotra Lab

Research Interests

The Malhotra Lab studies the molecular mechanisms by which atherosclerosis, vascular calcification, and arterial stiffness develop. Atherosclerosis and its downstream clinical consequences including myocardial infarction (MI), stroke, and peripheral vascular disease that affect more than 40 million people in the United States and is the number one cause of morbidity and mortality worldwide. Although treatments exist that target risk factors for cardiovascular disease, there is currently no treatment to directly prevent or reverse vascular calcification. Dr. Malhotra’s research program focuses on the role of multiple signaling pathways including histone deacetylases (HDACs), sulfatases, and bone morphogenetic proteins (BMPs) in the pathogenesis of vascular calcification and atherosclerosis. His laboratory has identified polymorphisms in the HDAC9 and ARSL loci that confer increased risk of vascular calcification in humans and has identified the mechanisms by which HDAC9 and ARSL promote calcification using both in vitro and in vivo approaches. Furthermore, his laboratory has demonstrated that pharmacologic inhibition of BMP signaling reduces the burden of vascular calcification, at least in part through inhibition of endothelial-to-mesenchymal transition. Additionally, his laboratory studies the biology and physiologic associations of iron homeostasis and the master regulator hepcidin (a downstream target of BMP signaling) in patients with cardiovascular disease. In a pipeline approach, Dr. Malhotra’s laboratory is also developing gene and small molecule therapies to treat vascular diseases.