NIH Director's Pioneer Award

这项研究有两个相辅相成的目标。第一个目标是 阐明更新人体组织的成体干细胞的生物学特性。这个 第二是将人类ASC的发现转化为细胞医学的进步。几十年来， 缺乏对ASCs的批判性知识一直是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构成了这堵墙。方法 由于缺乏对ASCs的准确鉴定，ASCs很难大量生产， 因此，ASCs的重要生物学特征仍然不清楚。要解决这些问题 在过去14年担任首席调查员期间，申请人承诺 对转基因小鼠细胞进行的研究，这种细胞模拟了 ASCS。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。申请者S实验室成立的一系列报告 利用小鼠ASC模型所做的发现与啮齿动物体内ASCs的相关性。这些 这些发现为识别ASCs奠定了创新基础，在 培养，并研究ASC的细胞和分子特性。借助NDPA支持， 申请者将改变他的研究计划的方向，由啮齿动物ASC研究组成，以 重点关注人类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、胰腺和头发的ASCs将是研究的重点 目标是开发细胞医学的临床前和临床应用。这个 申请者？S研究项目与来自不同国家的多个实验室合作 科学学科和技术领域，包括数学、染色体生物学、 质谱学、生物信息学、基因组学、电气工程、计算机科学和 电池产品行业。这些互动将补充研究，以扩大选定的 人类ASCs，开发工具准确识别它们，并将ASCs发展为有效的细胞 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.