Hematopoietic Stem Cells for Transplantation

描述(由申请者提供)：这项资助提案集中了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，以扩展对正常组织特异性干细胞和癌症干细胞的令人兴奋的新研究。PPG的研究人员期待着发现有关癌症干细胞定义特征的关键信息。这一知识将使我们能够开发新的方法，更好地鉴定和分离这些稀有细胞，以便进一步研究。此外，这项PPG旨在加深对癌症干细胞的病理生理机制的了解，特别是这些细胞持续生存和其他恶性行为所依赖的信号通路。这些基本信息将建议新的临床癌症干细胞靶点，我们将继续通过药理学和生物学方法进行攻击。无论是在项目内部还是在项目和核心之间的互动中，临床研究和实验室调查都将并行进行，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、紧密结合的翻译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疗法。 相关性：越来越多的证据表明，许多癌症起源于早期(干细胞或祖细胞)细胞，而成熟的癌症继续由干细胞-祖细胞层次结构维持。我们的团队提供了重要的证据，证明在人类疾病中存在离散的癌症干细胞群体，我们的结果支持这样的预测，即尽管成熟癌细胞的主要群体大幅减少，但化疗后患者的癌症复发可能是由于未能根除罕见的、持续的癌症干细胞群体。PPG的研究人员期待着发现有关癌症干细胞的定义特征和分子机制的关键信息，这些信息将为识别和攻击癌症干细胞提供新的治疗方法。

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.