Biorepository of Human iPSCs for Studying Dilated and Hypertrophic Cardiomyopathy

用于研究扩张型和肥厚型心肌病的人类 iPSC 生物储存库

基本信息

批准号：
8608017
负责人：
ATUL J BUTTE
金额：
$ 166.04万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-04-15 至 2019-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8608017
关键词：
Academia Address Adult Area Biology Businesses Cardiac Cardiac Myocytes Cardiotoxicity Cardiovascular Diseases Cardiovascular system Cell Line Cells Childhood Clinic Clinical Trials Communities DNA Data Development Developmental Biology Dilated Cardiomyopathy Disease Drug Industry Familial Hypertrophic Cardiomyopathy Feedback Fibroblasts Friends Future Generations Genes Genomics Genotype Goals Grant Heart Diseases Human Hypertrophic Cardiomyopathy Individual Industry Inherited Laboratories Medicine Methods Mind Mission Modeling Molecular Monoclonal Antibody R24 Mutation National Heart, Lung, and Blood Institute Patient Recruitments Patients Pharmaceutical Preparations Phenotype Population Genetics Preclinical Drug Evaluation Regenerative Medicine Reproducibility Research Research Personnel Research Project Grants Resource Sharing Resources Safety Sampling Technology Testing Time United States National Institutes of Health Vision abstracting biobank biomedical informatics cell bank clinical phenotype cohort drug discovery drug market genetic variant genome sequencing improved induced pluripotent stem cell interest large-scale database member molecular phenotype multidisciplinary next generation sequencing novel outreach program repository screening stem cell biology transcriptome sequencing

项目摘要

DESCRIPTION (provided by applicant): Familial dilated cardiomyopathy (DCM) and familial hypertrophic cardiomyopathy (HOM) are considered the two most common causes of inherited cardiovascular diseases. Previously, it has been difficult to study these diseases in human models because of limited access to human cardiomyocytes and difficulty growing them. With the discovery of human induced pluripotent stem cells (iPSCs) and the increased efficiency and reproducibility of differentiating them into beating cardiomyocytes (iPSC-CMs), the landscape has dramatically changed. For the first time, it is now possible to create patient-specific and disease-specific cell lines to improve our understanding of the molecular mechanisms of DCM and HCM. Hence the major goals of this multidisciplinary R24 Resource-Related Research Project are (i) generation, (ii) characterization, (iii) sequencing, and (iv) distribution of cardiac iPSC lines. Over the next 5 years, we plan to create an iPSC bank of 600 lines derived from control individuals, HCM patients, and DCM patients. To accomplish these goals, we have assembled a truly collaborative team of investigators with expertise in cardiovascular medicine, iPSC biology, developmental biology, next generation sequencing (NGS) technology, population genetics, biomedical informatics, large-scale database repository, and business development. We propose the following 4 Specific Aims over the next 5 years: Aim 1: To generate 600 iPSC lines from controls, DCM, and HCM patients. Aim 2: To evaluate drug safety screening using iPSCs ("clinical trial in a petri dish"). Aim 3: To obtain genotype-phenotype information using DNA-seq and RNA-seq. Aim 4: To distribute IPSC lines and their genotype-phenotype data to academic community. In summary, we believe this R24 will address a national need and fulfill NHLBI's strategic vision of creating a novel biorepository (iPSC-genotype-phenotype) that is valuable to the broader scientific community. Given our expertise and track record, we are confident we can deliver on these milestones. (End of Abstract)

描述（由申请人提供）：家族性扩张的心肌病（DCM）和家族性肥厚性心肌病（HOM）被认为是遗传性心血管疾病的两个最常见原因。以前，由于获得人类心肌细胞的机会有限并难以生长，因此很难在人类模型中研究这些疾病。随着人类诱导的多能干细胞（IPSC）的发现，以及将它们区分为击败心肌细胞（IPSC-CMS）的效率和可重复性的提高，景观发生了巨大变化。现在，可以首次创建患者特异性和疾病特异性细胞系，以提高我们对DCM和HCM分子机制的理解。因此，该多学科R24资源相关的研究项目的主要目标是（i）（ii）（ii）表征，（iii）测序和（iv）心脏IPSC线的分布。在接下来的5年中，我们计划创建一家IPSC银行，该银行由对照个体，HCM患者和DCM患者衍生而来。为了实现这些目标，我们组建了一个真正的合作调查人员团队，具有心血管医学，IPSC生物学，发展生物学，下一代测序（NGS）技术，人群遗传学，生物医学信息学，大规模数据库存储库和业务发展的专业知识。我们在未来5年中提出以下4个特定目标：目标1：从对照，DCM和HCM患者中生成600条IPSC线。 AIM 2：使用IPSC评估药物安全筛查（“培养皿中的临床试验”）。目标3：使用DNA-SEQ和RNA-SEQ获取基因型 - 表型信息。目标4：将IPSC线条及其基因型 - 表型数据分发给学术界。总而言之，我们认为该R24将满足国家需求，并满足NHLBI创建一种新颖的生物座席（IPSC-Genotype-phenotype）的战略愿景，该构想对更广泛的科学界有价值。鉴于我们的专业知识和记录，我们有信心我们可以实现这些里程碑。（抽象的结尾）