The Role of Glycosyl Ceramides in Heart Failure and Recovery

项目摘要/摘要 候选人：Eleni Tseliou，医学博士，盐湖城犹他大学(UU)心脏病学研究员 医生科学家培训计划(PSTP)的成员，目前是Dr.Drakos实验室的T32研究员 在诺拉·埃克尔斯·哈里森心血管研究和培训研究所(CVRTI)工作。Tseliou博士的研究 该项目的重点是脂肪酸(FA)代谢对心脏重构和心肌恢复的影响。 Tseliou博士的长期目标是独立领导一个由外部资助的实验室，专注于研究 关于影响心力衰竭(HF)和康复的代谢机制。职业发展：该奖项 将在Tseliou博士现有的心血管(CV)健康培训的基础上，支持她的职业发展 和疾病。Tseliou博士将接受关于调查研究的计划和执行的广泛培训 人、动物模型和体外心肌FA代谢的研究。职业发展计划概述了 协调努力，对候选人进行包括基于质谱学的脂组和代谢组学方面的培训 心力衰竭患者血清和组织的评估；心力衰竭转基因动物模型的建立和表型鉴定。手- 在学习和指导机会方面，将通过在当前主题上进行更广泛的培训来赞扬定期 参加教学课程(研究培训、研究互动、职业指导、出版物、研究 伦理学和奖助金撰写)分子心脏病学研讨会和会议。环境：犹他大学 是Tseliou博士职业发展的理想环境。CVRTI是一个独立的研究机构 位于UU健康科学中心，长期致力于促进和进步 简历生物学领域的早期研究人员。CVRTI的教职员工资金充裕，成绩优异。 指导初级内科科学家成为独立调查人员的记录。这个环境有一个 在基础和翻译简历研究方面有着悠久而丰富的历史，将为Tseliou博士提供 跨不同专业的协作机会以及完成建议的 学习。此外，UU和Dr.Drakos整合的基础科学和临床研究团队将为Dr. Tseliou有独特的机会对有和没有左心室辅助装置(LVAD)的患者进行表型 心肌恢复，谁是宝贵的连续人体心肌组织和血清的来源 治疗性干预。研究：该项目的中心假设是降低心脏特异性 UGCG(UDP-葡萄糖神经酰胺糖基转移酶)的表达 神经酰胺)导致FA代谢紊乱，易患心力衰竭。我们试图理解 造成这些现象的机制。虽然FA代谢的几种机制一直是 我们认为，有一些未知的途径受到神经酰胺改变的影响：GlcCer平衡为 它们与简历的健康和疾病有关。具体地说，我们假设UGCG在HF中的过度表达可能会有所帮助 逆转心肌肥厚和心室扩张，改善心功能，恢复心血管健康。

PROJECT SUMMARY/ABSTRACT Candidate: Eleni Tseliou, MD, PhD is cardiology fellow at the University of Utah (UU) in Salt Lake City as part of the Physician Scientist Training Program (PSTP) and currently a T32 research fellow at Dr. Drakos laboratory at the Nora Eccles Harrison Cardiovascular Research and Training Institute (CVRTI). Dr. Tseliou’s research project is focused on the impact of fatty acid (FA) metabolism on cardiac remodeling and myocardial recovery. Dr. Tseliou’s long-term goal is to independently direct an extramurally funded laboratory with research focused on metabolic mechanisms that affect cardiac heart failure (HF) and recovery. Career Development: This award will support Dr. Tseliou’s career development by building on her existing training in cardiovascular (CV) health and disease. Dr. Tseliou will receive extensive training in the planning and execution of studies investigating myocardial FA metabolism in humans, animal models and in vitro. The career development plan outlines a coordinated effort to train the candidate in areas including mass-spectrometry based lipidomic and metabolomic assessment of serum and tissue in HF; development and phenotyping of animal transgenic models of HF. Hands- on learning and mentoring opportunities will be complimented by broader training in current topics by regular attendance of didactic courses (research training, research interactions, career guidance, publications, research ethics and grant writing) molecular cardiology seminars and conferences. Environment: The University of Utah is an ideal environment for Dr. Tseliou’s career development. The CVRTI is a freestanding research institute located at the UU Health Sciences Center with a long-standing commitment to the promotion and advancement of early-career investigators in the field of CV biology. CVRTI faculty is well-funded and have excellent track records in mentoring junior physician-scientists to become independent investigators. This environment has a long and very rich history of excellence in basic and translational CV research and will provide Dr. Tseliou with the opportunity of collaboration across different specialties and the resources needed to complete the proposed studies. Moreover, the UU and Dr. Drakos integrated basic science and clinical research team will provide Dr. Tseliou with the unique opportunity to phenotype left ventricular assist devices (LVAD) patients with and without myocardial recovery, who are the source of precious serial human myocardial tissue and serum before and after the therapeutic intervention. Research: The central hypothesis of this project is that reduced cardiac specific expression of UGCG (UDP-glucose ceramide glucosyltransferase, a gene that catalyzes the glycosylation of ceramide) leads to the deregulation of FA metabolism and predisposes to HF. We seek to understand the mechanisms responsible for these phenomena. While several mechanisms of FA metabolism have been described, we contend that there are unexplored pathways influenced by altered ceramide:GlcCer balance as they relate to CV health and disease. Specifically, we hypothesize that UGCG overexpression in HF may help reverse cardiac hypertrophy and ventricular dilation, improve cardiac function and restore CV health.