The importance of Lysyl Oxidase in Atherosclerosis

摘要

Abstract This F32 fellowship award aims to facilitate the training and career transition of Dr. Filipe Fernandes Stoyell- Conti, Ph.D., an outstanding minority candidate, in vascular biology and atherosclerosis. Specifically, the grant offers to Dr. Fernandes Stoyell-Conti the possibility of improving his hands-on skills in the laboratory, strengthening his critical thinking and advancing his knowledge in bioinformatics and vascular biology. He will receive training while investigating the role of lysyl oxidase (LOX), a copper-dependent amine oxidase, in smooth muscle cells (SMCs) biology and atherosclerosis. Dr. Fernandes Stoyell-Conti research hypothesis is that LOX facilitates SMC cell migration, inflammation, and foam cell formation during atherogenesis. In three specific aims, he will: 1) investigate whether inactivation of LOX in SMCs compromises in vivo phenotypic switch of SMC, 2) demonstrate that expression of LOX in SMC increases atherosclerosis in hyperlipidemic mice, and 3) examine the molecular mechanisms by which LOX changes gene expression in SMCs. He will combine state of the art animal models, transcriptomics (RNA-seq) and molecular biology to demonstrate that LOX can “turn off/on” gene transcription in SMCs to make them more atherogenic. Together, these studies will advance his knowledge about LOX's role in atherosclerosis and facilitate his transition towards independence as principal investigator in the field of vascular biology and cardiovascular disease.