Research in my lab focuses on the role of the BMP/TGFβ signaling pathway in the maintenance of vascular homeostasis, control of vascular remodeling, and pathogenesis of vascular proliferative diseases, including idiopathic pulmonary arterial hypertension (IPAH), restenosis, and atherosclerosis. Our objective is to understand the molecular pathogenesis of vascular proliferative diseases as a result of deregulation of the signaling pathways which are critical for a control of vascular smooth muscle cells (vSMCs) phenotype and vascular remodeling. We are currently focusing on the following three projects.
#1: To understand the mechanism of regulation of miRNA biosynthesis by Smad proteins. We are investigating the mechanism of regulation of miRNA biosynthesis by TGFβs and BMPs, a process crucial to a more general understanding of the TGFβ/BMP-mediated phenotype switch underlying the pathogenesis of IPAH.
#2: To examine the role of miRNAs in the regulation of vSMC phenotype. We are exploring the potential in vivo role of miRNAs regulated by BMP/TGFβ or PDGF pathway in vascular remodeling in response to vascular injury, such as angioplasty.
#3: To understand the expression of miRNAs in peripheral blood in patients with cardiovascular diseases. It has been reported that miRNAs can be exported from cells in an exosome-dependent manner, stabilized, and hence detected in peripheral blood. More interestingly, serum or plasma samples from cancer patients exhibit a specific miRNA expression pattern different from serum samples from healthy individuals, suggesting that miRNA expression in peripheral blood might serve as a molecular signature of human disease and could be used as a diagnostic marker. In collaboration with Navin Kapur at Tufts Medical Center in Boston, we are investigating miRNA expression profile using serum samples from hypertrophic cardiomyopathy (HCM) patients, heart failure (HF) patients without HCM, patients with acute myocardial infarction (MI) as well as healthy donors.