The importance of Lysyl Oxidase in Atherosclerosis

摘要 这个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，他是血管生物学和动脉粥样硬化领域的杰出少数族裔候选人。具体来说， 为Fernandes Stoyell-Conti博士提供了提高其实验室动手能力的可能性， 加强他的批判性思维和推进他在生物信息学和血管生物学的知识。他将 接受培训，同时研究赖氨酰氧化酶（LOX），铜依赖性胺氧化酶，在光滑 肌细胞（SMC）生物学和动脉粥样硬化。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的体内表型转换，2） 证明了LOX在SMC中的表达增加了高血脂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。他将联合收割机 动物模型，转录组学（RNA-seq）和分子生物学来证明LOX可以“关闭/打开”基因， 使其更易致动脉粥样硬化。总之，这些研究将促进他的知识， LOX在动脉粥样硬化中的作用，并促进他作为主要研究者的独立性， 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.