The Laboratory of Rajeev Malhotra, MD, MS

About the Lab

The Malhotra Lab, led by Rajeev Malhotra, MD, MS, as part of the Anesthesia Center for Critical Care Research, studies the molecular mechanisms by which atherosclerosis and calcification develop in the vessel wall in the hopes of uncovering novel targets for the development of new disease treatments.

Atherosclerosis and its downstream clinical consequences including myocardial infarction (MI), stroke and peripheral vascular disease affect more than 40 million people in the United States and is the number one cause of morbidity and mortality worldwide. Atherosclerotic plaques build up on the walls of blood vessels and consist of lipids and calcium deposits. Although treatments exist that target risk factors for cardiovascular disease (such as dyslipidemia or anti-hypertensives), there is currently no treatment to directly prevent or reverse vascular calcification.

Dr. Malhotra’s research program focuses on the role of histone deacetylases (HDACs), autophagy, matrix Gla protein and bone morphogenetic proteins (BMPs) in the pathogenesis of vascular calcification and atherosclerosis. His laboratory has identified polymorphisms in the HDAC9 locus that confer increased risk of vascular calcification, MI and stroke in humans and have demonstrated that HDAC9 promotes vascular calcification using both in vitro and in vivo models. Furthermore, his laboratory has demonstrated that pharmacologic inhibition of BMP signaling reduces the burden of vascular calcification, likely through inhibition of endothelial-to-mesenchymal transition. More recently, Dr. Malhotra’s laboratory has identified an essential role for matrix Gla protein in regulating arterial stiffness. Using a combination of human genetic and biomarker approaches, vascular smooth muscle cell and endothelial cell assays, and in vivo models, Dr. Malhotra’s laboratory aims to identify novel genetic and molecular mechanisms of cardiovascular disease.