NIH Director's Pioneer Award

这项研究有两个互补的目标。第一个目标是 阐明更新人体组织的成体干细胞（ASC）的生物学特性。的 第二是将人类ASC的发现转化为细胞医学的进步。几十年来， 缺乏关于ASC的关键知识一直是ASC前沿的一堵可怕的墙 研究和细胞医学。三个棘手的研究挑战形成了这堵墙。方法 缺乏对ASC的精确鉴定，ASC难以大量生产， 因此，ASC的重要生物学特征仍不清楚。解决这些 挑战，在过去的14年中，作为主要研究者，申请人承诺 用基因工程小鼠细胞进行的研究， ASC。这些特性是不对称的自我更新和不朽的DNA链共分离， ASCs的两个定义特征。申请人的一系列报告？实验室成立 用小鼠ASC模型发现的与啮齿动物体内ASC的相关性。这些 这些发现为识别ASC奠定了创新基础， 培养，并研究ASC的细胞和分子特性。通过NDPA支持， 申请人将改变他的研究计划的方向，与啮齿动物ASC研究锻造， 专注于人类ASCs及其向胚胎干细胞（ESC）样细胞的转化。人类 负责肝脏、造血细胞、胰腺、毛发的ASC将成为研究重点 其目标是开发细胞医学的临床前和临床应用。的 申请人？的研究计划享有与来自不同的几个实验室合作 科学学科和技术领域，包括数学，染色体生物学， 质谱、生物信息学、基因组学、电子工程、计算机科学，以及 电池产品行业。这些互动将补充研究，以扩大选定的 人ASC，开发用于其精确鉴定工具，并将ASC作为有效的细胞 治疗人类疾病的药物。

The research proposed has two complementary goals. The first goal is to elucidate the biological properties of adult stem cells (ASCs) that renew human tissues. The second is to translate human ASC discoveries into advances in cellular medicine. For decades, lack of critical knowledge about ASCs has been a formidable wall at the frontier of ASC research and cellular medicine. Three intractable research challenges form this wall. Methods for exact identification of ASCs are lacking, ASCs are difficult to produce in large quantities, and, therefore, important biological features of ASCs remain obscure. To address these challenges, during the past 14 years as a principal investigator, the applicant undertook research with genetically-engineered mouse cells that modeled essential unique properties of ASCs. These properties are asymmetric self-renewal and immortal DNA strand co-segregation, two defining features of ASCs. A series of reports from the applicant?s laboratory established the relevance of discoveries made with the mouse ASC models to rodent ASCs in vivo. These discoveries established an innovative foundation for identifying ASCs, expanding ASCs in culture, and investigating ASC cellular and molecular properties. With NDPA support, the applicant will change the direction of his research program, forged with rodent ASC studies, to focus on human ASCs and their conversion into embryonic stem cell (ESC)-like cells. Human ASCs responsible for liver, hematopoietic cells, pancreas, and hair will be the focus of research with the goal of developing both pre-clinical and clinical applications for cellular medicine. The applicant?s research program enjoys collaborations with several laboratories from diverse scientific disciplines and technological fields, including mathematics, chromosome biology, mass spectrometry, bioinformatics, genomics, electrical engineering, computer sciences, and the cell products industry. These interactions will complement research to expand selected human ASCs, develop tools for their exact identification, and advance ASCs as effective cellular medicines for human disease.