Hematopoietic Stem Cells for Transplantation

描述（由申请人提供）：这项拨款提案集中于我们在动物和人类干细胞生物学和白血病方面的持续实验室和临床研究经验，以扩展正常组织特异性和癌症干细胞的令人兴奋的新研究。该PPG的研究人员期待发现有关癌症干细胞定义特征的关键信息。这些知识将使我们能够开发新的方法来更好地鉴定和分离这些稀有细胞，以供进一步研究。此外，本PPG旨在增加对癌症干细胞病理生理机制的理解，特别是这些细胞依赖于其持久性和其他恶性行为的信号通路。这些基本信息将提示新的临床肿瘤干细胞靶点，我们将通过药理学和生物学方法进行攻击。在项目内部以及项目和核心之间的互动中，临床研究和实验室调查将并行进行，以便在一个领域产生的见解将转化为并促进另一个领域的进展。我们相信，我们高度互动，紧密结合，翻译的方法是确定正常和恶性干细胞生物学机制的最佳途径，同时开发利用正常干细胞和针对人类疾病的恶性干细胞的新治疗方法。

DESCRIPTION (provided by applicant): This grant proposal focuses our sustained laboratory and clinical research experience in animal and human stem cell biology and leukemia to extend exciting new investigations on normal tissue-specific and cancer stem cells. The investigators in this PPG look forward to discovering key information about the defining characteristics of cancer stem cells. This knowledge will enable us to develop new methods to better identify and isolate these rare cells for further study. In addition, this PPG seeks increased understanding of the pathophysiologic mechanisms of cancer stem cells, particularly the signaling pathways that these cells depend on for their persistence and other malignant behavior. This basic information will suggest new clinical cancer stem cell targets, which we will proceed to attack via pharmacologic and biologic approaches. Both within the Projects and in interactions among the Projects and Cores, clinical research and laboratory inquiries will proceed in parallel, so that insights generated in one sphere will translate to, and promote progress in the other. We believe that our highly interactive, closely integrated, translational approach is the best way to determine mechanisms of normal and malignant stem cell biology, and simultaneously to develop new treatments utilizing normal stem cells and targeting malignant stem cells in human diseases. Relevance: There is growing evidence suggesting that many cancers originate in early (stem or progenitor) cells and that the mature cancers continue to be maintained by a stem-progenitor cell hierarchy. Our group has provided important evidence demonstrating the existence of discrete populations of cancer stem cells in human diseases, and our results support the prediction that cancer recurrence in patients after chemotherapy may be due to failure to eradicate the rare, sustaining cancer stem cell population, despite massive reduction of the predominant bulk population of mature cancer cells. The investigators in this PPG look forward to discovering key information about the defining characteristics and molecular mechanisms of cancer stem cells that will provide new ways to identify and attack cancer stem cells therapeutically.