Functional role of microRNA in acute myeloid leukemia stem cells and their normal

描述(由申请人提供)：这份为期5年的建议书描述了在实验病理学领域的职业发展的综合计划。这位首席研究员在斯坦福大学完成了解剖病理学住院医师和血液病理学研究员培训，并在过去两年里一直在磨练自己作为诊断血液病理学家的技能，同时将大部分时间花在培养技术和智力技能上，这将使他成为一名独立的研究员。 拟议的工作将在欧文·L·魏斯曼的实验室进行，他是干细胞生物学、癌症干细胞生物学和造血领域的国际公认领导者。考虑到智力和技术资源的广度和深度，魏斯曼博士的实验室代表着一个独特的环境，不仅是为了让极具创造性和创新性的项目取得成果，也是为了培训未来的独立调查人员。 鉴于越来越多的证据表明microRNAs在人类癌症的发展中发挥了作用，这一建议代表着对人类急性髓系白血病(AML)发病机制的及时研究。与传统的癌症生物学研究不同，拟议的研究将专注于AML的肿瘤启动或干细胞。由于白血病干细胞(LSC)的独特特性，包括在异种移植模型中启动肿瘤、自我更新和重复性疾病的能力，我们迫切需要了解AML LSC生物学特性的分子基础。由于与原始人类样本相关的独特实验挑战，已经并将继续投入大量时间来开发改进的模型，以研究microRNAs在人类急性髓细胞白血病中的作用。 斯坦福干细胞生物学和再生医学研究所是进行这些研究的理想场所。除了容纳癌症和干细胞生物学家社区外，还有许多机会通过跨学科项目与其他部门的成员合作，包括斯坦福综合癌症中心、免疫学项目和许多其他项目。鉴于斯坦福大学临床科室的实力(成人和儿童血液学/肿瘤学、骨髓移植、血液病理学)，有大量的组织接触以及与临床同事合作的机会。

DESCRIPTION (provided by applicant): This 5 year-proposal describes a comprehensive plan for the development of a career in experimental pathology. The principal investigator completed anatomic pathology residency and hematopathology fellowship training at Stanford University and has spent the past two years honing his skills as a diagnostic hematopathologist while spending the majority of his time developing the technical and intellectual skills that will allow him to become an independent investigator. The proposed work will take place in the laboratory of Irving L. Weissman, an internationally recognized leader in the field of stem cell biology, cancer stem cell biology, and hematopoiesis. Given the breadth and depth of intellectual and technological resources, Dr. Weissman's lab represents a unique environment, geared not only to allowing highly creative and innovative projects to come to fruition, but also to train future independent investigators. Given the growing evidence that microRNAs play a role in the development of human cancers, this proposal represents a timely investigation into the pathogenesis of human acute myeloid leukemia (AML). Unlike conventional cancer biology research, the proposed studies will focus on the tumor-initiating, or stem cells, of AML. Because of the unique properties of leukemia stem cells (LSC), including the capacity to initiate tumors, self-renew, and recapitulate disease in xenograft models, it is imperative that we understand the molecular basis of the AML LSC biologic properties. Because of the unique experimental challenges associated with working with primary human samples, a great deal of time has been, and will continue to be, invested in developing improved models to study the role of microRNAs in human AML. The Stanford Institute for Stem Cell Biology and Regenerative Medicine is an ideal setting for these studies. In addition to housing a community of cancer and stem cell biologists, there are numerous opportunities to collaborate with members of other departments through interdisciplinary programs including the Stanford Comprehensive Cancer Center, Immunology Program, and many others. Given the strength of Stanford's clinical divisions (adult and pediatric hematology/oncology, bone marrow transplant, hematopathology), there is significant tissue access as well as opportunities to work with clinical colleagues.