Lipid signaling in cardiac development and disease

项目总结 该提案包含一项详细的五年培训计划，用于指导职业生涯发展 在生物医学研究中代表不足的少数群体，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，并提议 专门设计的研究方向，旨在为他向 独立的学术研究生涯。通过这项提案中包含的职业和科学计划， 申请者的目标是利用他之前在干细胞生物学和心脏开发方面的培训，最近获得了 掌握基于质谱学的脂类组学、大数据集分析、高含量筛选和 在结构良好和有指导的科学环境中建立心血管疾病模型，以便 了解心脏发育和疾病过程中心肌细胞内二十烷类化合物的变化。一个 华盛顿大学内科专家兼科学家莫希特·贾恩博士建立了联合导师关系 加州圣地亚哥，拥有代谢组学、系统分析和基因组学方面的专业知识，陈菊博士，一位 干细胞生物学、心脏生理学和疾病方面的世界专家，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者提供良好的环境， 拥有最先进的基础设施、分析技能和无数资源，以获得必要的 训练。Jain博士和Chen博士都有良好的导师记录，包括年轻的研究人员 过渡到教员职位或作为独立研究人员。申请者已经汇集了一位专家 加州大学圣地亚哥分校杰出科学家和临床医生及外部研究学术咨询委员会 社区之间相互指导和补充科学专门知识。此外，申请人亦已 获得加州大学圣迭戈分校的Mark Lawson博士的咨询支持，以进行公平和整合方面的培训 少数群体在生物医学科学中的代表性不足。这项提案的中心目标是：1)调查 在心脏干细胞分化和心脏发育过程中二十烷类途径的激活，2)鉴定 促进心肌细胞分化的特定二十烷基类化合物，以及3)探讨 二十烷类信号通路在心力衰竭中的作用。申请者将利用一种创新的质谱学- 基于二十烷类化合物图谱平台，配以体外高含量分析工具，系统分析，状态- ART干细胞分化技术和体内小鼠心脏发育和心脏模型 疾病。这些目标将有助于整合发现方法和假设驱动的研究。这个 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生涯。

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.