The Effect of Saturated Fat Ingestion on the HDL Proteome

描述（由申请人提供）：饱和脂肪摄入对高密度脂蛋白蛋白质组的影响候选人：Hussein Yassine在凯斯西储大学完成了他的住院医师培训，并在John Kirwan博士的施瓦茨代谢中心进行了运动生理学的额外研究培训。随后，他加入了亚利桑那大学的内分泌学项目，并在Serrine Lau博士的指导下接受了蛋白质组学研究的培训。Yassine博士对转化研究有浓厚的兴趣。他目前是亚利桑那大学的助理教授。职业目标：亚辛博士的职业目标是成为一名杰出的内科科学家。目标是通过推进心血管研究，为科学社会做出贡献并提供优质的患者护理来实现。机构：亚利桑那大学拥有最先进的蛋白质组学联盟和实验室。Serrine Lau博士是世界知名的毒理学家和亚利桑那蛋白质组学协会的主任，对使用最先进的蛋白质组学技术发现生物标志物有浓厚的兴趣。指导团队和教师角色：Dr. Serrine Lau是申请人的主要导师，并将在奖励阶段负责推进申请人的职业发展。刘博士培养了一大批目前活跃、独立、成功的科学家。Drs。George Tsaprailis和Linda Breci（蛋白质组学核心）将通过课程和实践研讨会提供蛋白质组学方面的培训。内分泌学主任兼氧化应激专家Craig Stump博士和脂质紊乱专家Stanley Goldberg博士将在临床研究中提供指导，并将确保Yassine博士拥有发展成为独立内科科学家的资源。迪恩·比尔海默博士是生物标志物发现的生物统计学专家，他致力于通过正式会议、讲习班和研讨会来发展亚辛博士的生物统计学背景。申请人将向Peter Reaven博士咨询临床队列设计、炎症和心血管疾病。一个由成功获得资助的科学家（博士）组成的顾问小组。Price, Funk, Vercelli)的成立是为了评估研究进展并向独立过渡。项目描述：高密度脂蛋白，或好胆固醇，被认为是预测死亡、心脏病发作和中风最重要的血液指标之一。HDL预防动脉粥样硬化和心血管疾病的机制尚不清楚。HDL由一个脂质核心和一系列与炎症和血凝块形成有关的附着蛋白组成。饮食中摄入饱和脂肪会增加患心血管疾病的风险，高密度脂蛋白胆固醇浓度会适度增加，但对高密度脂蛋白附着蛋白的影响尚不清楚。我们假设患有糖尿病和心血管疾病的受试者具有富含炎症和血栓形成前蛋白的HDL，并且饱和脂肪饮食产生富含炎症蛋白的HDL颗粒。亚利桑那大学拥有世界著名的蛋白质组学研究设施，可以发现非常低浓度的蛋白质。我们的第一个目标是利用蛋白质组学技术鉴定有或没有糖尿病和心血管疾病的受试者的HDL蛋白质组表型。我们的第二个目标是确定摄入一杯浓奶油后高密度脂蛋白的变化。这一发现可以帮助我们了解心血管疾病中HDL的组成变化，并作为开发旨在减轻心血管疾病负担的新疗法的标志。

DESCRIPTION (provided by applicant): The Effect of Saturated Fat Ingestion on the HDL Proteome The candidate: Hussein Yassine completed his residency at Case Western Reserve University with additional research training in exercise physiology at Schwartz Center of Metabolism by Dr. John Kirwan. He then joined the endocrinology program at the University of Arizona and trained in proteomics research under the supervision of Dr. Serrine Lau. Dr. Yassine has a strong interest in translational research. He is currently an Assistant Professor at the University of Arizona. Career Goals: Dr. Yassine's career goal is to be an outstanding physician-scientist. The goal is achieved by advancing cardiovascular research, contributing to the scientific society and providing excellent patient care. Institution: The University of Arizona has a state-of-the-art proteomics consortium and laboratory. Dr. Serrine Lau is a world renowned toxicologist and the director of the Arizona Proteomics Consortium with a strong interest in biomarker discovery using state-of-the art proteomic technology. Mentoring Team and Faculty Roles: Dr. Serrine Lau is the applicant's primary mentor, and will be responsible for advancing the applicant's career during the award phase. Dr. Lau has trained a large number of currently active, independent and successful scientists. Drs. George Tsaprailis and Linda Breci (proteomics core) will provide training in proteomics through courses, and hands on workshops. Dr. Craig Stump, Chief of Endocrinology and an expert in oxidative stress, and Dr. Stanley Goldberg, an expert in lipid disorders, will provide mentorship in clinical research, and will ensure that Dr. Yassine will have the resources to develop into an independent physician-scientist. Dr. Dean Billheimer, an expert in biostatistics for biomarker discovery, is committed to developing Dr. Yassine's biostatistics background through formal meetings, workshops and seminars. The applicant will consult with Dr. Peter Reaven on clinical cohort design, inflammation and cardiovascular disease. An advisory team of successfully funded scientists (Drs. Price, Funk, Vercelli) is formed to assess research progress and transitioning into independence. Project description: HDL, or good cholesterol, is considered one of the most important blood measures in predicting death, heart attacks and strokes. The mechanism of how HDL protects against atherosclerosis and cardiovascular disease is poorly understood. HDL consists of a lipid core and a wide array of attached proteins involved in inflammation and blood clot formation. Saturated fat intake in the diet increases the risk of cardiovascular disease with modest increases in HDL cholesterol concentrations, but its effect on HDL attached proteins is not known. We hypothesize that subjects with diabetes and cardiovascular disease have HDL enriched with inflammatory and prothrombotic proteins, and that a saturated fatty diet generates an HDL particle enriched in inflammatory proteins. The University of Arizona possesses a world- renowned proteomics research facility that discovers proteins at very low concentrations. Our first aim is to employ proteomic technologies to identify HDL proteome phenotypes in subjects with and without diabetes and cardiovascular disease. Our second aim is to identify the changes of the HDL protein cargo after ingesting a cup of heavy whipped cream. This discovery could help us understand the composition changes of HDL involved in cardiovascular disease, and serve as a marker to develop novel therapies aimed at decreasing the cardiovascular disease burden.