The Role of Glycosyl Ceramides in Heart Failure and Recovery

糖基神经酰胺在心力衰竭和恢复中的作用

基本信息

批准号：
10644874
负责人：
Eleni Tseliou
金额：
$ 17.93万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-01 至 2028-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10644874
关键词：
Address Adult Affect Amino Acids Animal Model Apoptosis Area Attention Award Basic Science Binding Sites Biochemical Biology Carbohydrates Cardiac Cardiac Myocytes Cardiology Cardiomyopathies Cardiovascular Diseases Cardiovascular system Cause of Death Cell Aging Cell Proliferation Cell physiology Cellular biology Ceramide glucosyltransferase Ceramides Cities Clinical Clinical Research Collaborations Coupled Data Dependovirus Development Development Plans Devices Disease Doctor of Philosophy Endocytosis Environment Equilibrium Evaluation Extramural Activities Faculty Fatty Acids Fibrosis Funding Gene Expression Genes Genetic Models Glycolysis Goals Health Sciences Heart Hypertrophy Heart failure Histology Human Hypertrophy Impairment In Vitro Inflammation Insulin Resistance Intracellular Transport Junior Physician Laboratories Link Lipids Liver Mass Spectrum Analysis Mediating Mentors Metabolic Metabolism Modeling Molecular Morbidity - disease rate Mus Myocardial Myocardial tissue Myocardium Oxidative Phosphorylation Pathogenesis Pathologic Pathway interactions Patients Phenotype Play Population Production Publications Pump RXR Recording of previous events Records Recovery Reporting Research Research Ethics Research Institute Research Personnel Research Project Grants Research Training Resources Role Scientist Serum Sodium Chloride Source Sphingolipids Sphingomyelins Sphingosine Structure Subgroup Testing Therapeutic Intervention Time Tissues Training Transcription Alteration Transcriptional Regulation Transgenic Animals Transgenic Model Universities Utah Ventricular Vocational Guidance Writing cardiovascular health career career development cell growth cell motility cohort coping economic impact fatty acid metabolism flexibility functional improvement gene conservation glycosylation hands-on learning heart function implantation improved improved outcome insight left ventricular assist device lipidomics medical specialties metabolic phenotype metabolomics mortality mouse model novel novel therapeutic intervention novel therapeutics overexpression personalized medicine physician-scientist training program prevent promoter response symposium transcription factor transcriptomics

项目摘要

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.

项目摘要/摘要候选人：医学博士Eleni Tseliou是盐湖城犹他大学（UU）的心脏病学研究员医师科学家培训计划（PSTP），目前是Drakos博士实验室的T32研究员在Nora Eccles Harrison心血管研究与培训研究所（CVRTI）。 Tseliou博士的研究项目的重点是脂肪酸（FA）代谢对心脏重塑和心肌恢复的影响。 Tseliou博士的长期目标是独立指导一个以研究为重点的实验室的实验室关于影响心脏心力衰竭（HF）和恢复的代谢机制。职业发展：这个奖项将通过在心血管（CV）Health中进行现有培训来支持Tseliou博士的职业发展和疾病。 Tseliou博士将在计划和执行研究的计划和执行方面接受广泛的培训人类，动物模型和体外的心肌FA代谢。职业发展计划概述了协调训练候选人在包括质谱基脂肪组和代谢组在内的领域的训练评估HF中的血清和组织； HF动物转基因模型的开发和表型。 hands 在学习和心理机会方面，将通过常规主题进行更广泛的培训来补充教学课程的出席（研究培训，研究互动，职业指导，出版物，研究伦理和授予写作）分子心脏病学的半手和会议。环境：犹他大学是Tseliou博士职业发展的理想环境。 CVRTI是一家独立研究所位于UU健康科学中心，对晋升和晋升有长期的承诺 CV生物学领域的早期研究人员的研究人员。 CVRTI教职员工资金充足，轨道很棒心理少年身体科学家成为独立研究人员的记录。这个环境有一个长期且非常丰富的基础和翻译简历研究卓越历史，并将为Tseliou博士提供跨不同专业的合作机会以及完成建议的资源研究。此外，UU和Drakos博士综合基础科学和临床研究团队将为博士提供。 tseliou有独特的机会左心室辅助设备（LVAD）患者有或没有心肌恢复，是珍贵的人类心肌组织和血清之前和之后的血清的来源治疗干预。研究：该项目的中心假设是减少心脏特异性 UGCG的表达（UDP-葡萄糖神经酰胺葡萄糖基转移酶，该基因催化促糖基化的基因神经酰胺导致FA代谢并易于HF。我们试图了解负责这些现象的机制。虽然已经有几种FA代谢的机制描述的是，我们认为存在着改变神经酰胺的意外途径：Glccer平衡为它们与简历健康和疾病有关。具体而言，我们假设HF中的UGCG过表达可能有助于反向心脏肥大和心室扩张，改善心脏功能并恢复简历健康。