The importance of Lysyl Oxidase in Atherosclerosis

摘要 这项F32奖学金旨在促进Filipe Fernandes Stoyell博士的培训和职业过渡- 孔蒂博士，杰出的少数族裔候选人，研究血管生物学和动脉粥样硬化。具体地说，赠款 向费尔南德斯·斯托耶尔-孔蒂博士提出了在实验室提高他的动手技能的可能性， 加强批判性思维，推进生物信息学和血管生物学知识。他会的 接受培训，同时研究赖氨酰氧化酶(LOX)，一种铜依赖的胺氧化酶在平滑中的作用 肌细胞生物学与动脉粥样硬化。Fernandes Stoyell-Conti博士的研究假设是LOX 在动脉粥样硬化形成过程中促进SMC细胞迁移、炎症和泡沫细胞的形成。在三个具体目标中， 他将：1)研究SMC中LOX的失活是否会影响SMC体内的表型转换，2) 证明LOX在SMC中的表达增加了高脂血症小鼠的动脉粥样硬化，以及3)检查 LOX改变SMC基因表达的分子机制。他将结合最先进的技术 动物模型、转录学(RNA-seq)和分子生物学证明LOX可以“关闭/开启”基因 在SMC中转录，使它们更容易导致动脉粥样硬化。总而言之，这些研究将促进他对 LOX在动脉粥样硬化中的作用，并促进他向独立的过渡，成为 血管生物学和心血管疾病领域。

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.