Lipid signaling in cardiac development and disease

心脏发育和疾病中的脂质信号传导

• 批准号: 9229453
• 负责人: Aitor Aguirre
• 金额: $ 18.15万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-15 至 2021-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9229453
• 关键词: Achievement; Adult; Advisory Committees; Anabolism; Arachidonic Acids; Automobile Driving; Biochemistry; Biomedical Research; California; Cardiac; Cardiac Myocytes; Cardiac development; Cardiovascular Diseases; Cardiovascular Models; Cardiovascular system; Cause of Death; Cell model; Communities; Complement; Cues; Data; Data Set; Development; Disease; Disease model; Echocardiography; Eicosanoid Production; Eicosanoids; Elements; Endothelin-1; Environment; Enzymes; Faculty; Family; Fostering; Funding; Gene Expression; Gene Expression Profile; Gene Silencing; Genes; Genomics; Goals; Grant; Growth; Growth and Development function; Heart; Heart Diseases; Heart Hypertrophy; Heart failure; Histologic; Human; Hypertrophy; In Vitro; Inflammation; Joints; K-Series Research Career Programs; Laboratories; Link; Lipids; Mass Spectrum Analysis; Measurement; Mediating; Mediator of activation protein; Mentors; Mentorship; Methods; Molecular; Molecular Profiling; Mus; National Heart, Lung, and Blood Institute; Pathway interactions; Pharmacology; Phospholipids; Physicians; Physiology; Play; Positioning Attribute; Process; Regulator Genes; Research; Research Infrastructure; Research Personnel; Resources; Role; Science; Scientist; Signal Pathway; Signal Transduction; Stem cells; Structure; Systems Analysis; Techniques; Technology; Time; Training; Training Programs; Underrepresented Minority; Universities; Up-Regulation; autocrine; base; cardiogenesis; career; career development; constriction; design; enzyme biosynthesis; experience; fetal; heart cell; in vivo; in vivo Model; induced pluripotent stem cell; innovation; insight; interest; lipid mediator; liquid chromatography mass spectrometry; metabolomics; minority investigator; mortality; mouse model; novel; novel therapeutic intervention; overexpression; paracrine; pressure; programs; screening; secondary analysis; skills; stem cell biology; stem cell differentiation; tool; transcription factor

PROJECT SUMMARY This proposal contains a detailed five-year training program for mentored career development of a underrepresented minority in biomedical research, with a focus on cardiovascular disease and lipid signaling. The Applicant has completed training in cardiovascular development and stem cell biology and is proposing a research direction specifically designed to provide additional essential training for his transition towards an independent academic research career. Through the career and scientific plans contained in this proposal, the Applicant aims to leverage his prior training in stem cell biology and cardiac development, with newly acquired skills in mass spectrometry-based lipidomics, large-dataset analysis, high-content screening and cardiovascular disease models within a well-structured and mentored scientific environment, in order to understand the eicosanoid changes that occur in cardiomyocytes during heart development and disease. A joint mentorship has been established between Dr. Mohit Jain, an expert physician-scientist at the University of California San Diego with expertise in metabolomics, systems analysis and genomics, and Dr. Ju Chen, a world expert in stem cell biology, cardiac physiology and disease, to foster the Applicant's scientific and career development. Dr. Jain's and Dr. Chen's laboratories will provide an excellent environment for the applicant, with state-of-the-art infrastructure, analytical skills and innumerable resources required to obtain the necessary training. Both Dr. Jain and Dr. Chen have a proven track record of mentorship, including young investigators transitioning to faculty positions or as independent researchers. The Applicant has put together an expert academic advisory committee of distinguished scientists and clinicians from UCSD and external research communities to guide and complement each other's scientific expertise. Furthermore, the Applicant has also enlisted the advisory support of Dr. Mark Lawson, from UCSD, for training in equity and integration of minorities underrepresented in biomedical sciences. The central goals of this proposal are to 1) investigate activation of the eicosanoid pathway during cardiac stem cell differentiation and heart development, 2) identify specific eicosanoid species that drive cardiomyocyte differentiation, and 3) explore the contribution of eicosanoid signaling pathways in heart failure. The Applicant will utilize an innovative mass spectrometry- based eicosanoid profiling platform, together with in vitro high-content analysis tools, systems analysis, state- of-the art stem cell differentiation techniques and in vivo mouse models of heart development and cardiac disease. These aims will serve to integrate discovery approaches and hypothesis-driven research. The experience obtained from the proposed training and career development will serve as the basis for the Applicant's independent career as scientist.

项目摘要 该提案包含一个详细的五年培训计划， 在生物医学研究中，少数人的代表性不足，重点是心血管疾病和脂质信号。 申请人已完成心血管发育和干细胞生物学方面的培训， 研究方向专门设计，以提供额外的必要培训，他向一个 独立的学术研究生涯。通过本提案所载的职业和科学计划， 申请人旨在利用他先前在干细胞生物学和心脏发育方面的培训， 在基于质谱的脂质组学，大数据集分析，高内容筛选和 心血管疾病模型在一个良好的结构和指导的科学环境，以 了解在心脏发育和疾病过程中心肌细胞中发生的类花生酸变化。一 联合指导已经建立之间的Mohit Jain博士，一个专家医生，科学家在大学 加州圣地亚哥的代谢组学，系统分析和基因组学的专业知识，和朱陈博士， 世界干细胞生物学，心脏生理学和疾病专家，以促进申请人的科学和职业生涯 发展Jain博士和Chen博士的实验室将为申请人提供良好的环境， 拥有最先进的基础设施、分析技能和无数资源， 训练贾恩博士和陈博士都有良好的指导记录，包括年轻的研究人员 过渡到教师职位或作为独立的研究人员。申请人已召集专家 来自UCSD和外部研究的杰出科学家和临床医生的学术咨询委员会 社区指导和补充彼此的科学专业知识。此外，申请人还 获得了加州大学圣地亚哥分校马克·劳森博士的咨询支持，进行平等和融合的培训。 少数群体在生物医学科学领域的代表性不足。该提案的主要目标是：1）调查 在心脏干细胞分化和心脏发育过程中类花生酸途径的激活，2）鉴定 驱动心肌细胞分化的特定类花生酸种类，以及3）探索 类花生酸信号通路在心力衰竭中的作用申请人将利用创新的质谱法- 基于类花生酸分析平台，连同体外高含量分析工具，系统分析，状态分析， 现有技术的干细胞分化技术和心脏发育和心脏发育的体内小鼠模型 疾病这些目标将有助于整合发现方法和假设驱动的研究。的 从拟议的培训和职业发展中获得的经验将作为 申请人作为科学家的独立职业。