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The importance of Lysyl Oxidase in Atherosclerosis

赖氨酰氧化酶在动脉粥样硬化中的重要性

基本信息

批准号：
10543402
负责人：
Filipe Fernandes Stoyell-Conti
金额：
$ 8.09万
依托单位：
UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-02-01 至 2025-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10543402
关键词：
Adult Affect American Animal Model Animals Area Arterial Occlusive Diseases Arteries Atherosclerosis Award Belief Bioinformatics Biology Blood Vessels Breeding Cardiovascular Diseases Career Mobility Cause of Death Cell Nucleus Cells Cellular biology Collagen Complex Confocal Microscopy Copper Coronary Arteriosclerosis Critical Thinking Data Analyses Deposition Development Disease Doctor of Philosophy Elastin Enzymes Extracellular Matrix Fellowship Foam Cells Gene Expression Gene Silencing Genes Genetic Transcription Goals Grant Histology Immunofluorescence Immunologic In Vitro Inflammation Knock-in Mouse Knowledge Label Laboratories Lesion Lipids Location Mentors Microdissection Minority Molecular Molecular Biology Molecular Biology Techniques Molecular Cloning Mus Mutagenesis Peripheral arterial disease Phenotype Principal Investigator Protein-Lysine 6-Oxidase Research Risk Risk Reduction Role Rupture Smooth Muscle Myocytes Systems Biology Tamoxifen Testing Time Training Transgenic Mice Western World amine oxidase atherogenesis cell dedifferentiation cell motility cerebrovascular crosslink disability effective therapy gain of function healing improved in vivo lentivirally transduced loss of function migration monomer mouse model novel novel therapeutics overexpression prevent skills thrombotic transcriptome sequencing transcriptomics ultrasound microscopy

项目摘要

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.

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。