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

microRNA在急性髓系白血病干细胞及其正常状态中的功能作用

• 批准号: 7666098
• 负责人: CHRISTOPHER Y PARK
• 金额: $ 13.75万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-03 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7666098
• 关键词: Accounting; Acute Myelocytic Leukemia; Adult; Anatomy; Antibody Therapy; Apoptosis; Biological Assay; Blast Cell; Bone Marrow Transplantation; Cancer Biology; Cell physiology; Cell surface; Cells; Chromosomal translocation; Chronic Myeloid Leukemia; Chronic Phase; Clinical; Commit; Communities; Comprehensive Cancer Center; Crowding; Culture Techniques; Data; Daughter; Development; Development Plans; Developmental Process; Diagnosis; Diagnostic; Disease; Engraftment; Environment; Epigenetic Process; Event; Exhibits; Experimental Pathology; Fellowship; Figs - dietary; Future; Gene Fusion; Gene Mutation; Gene Targeting; Genes; Genetic; Genome Stability; Goals; Hematopathology; Hematopoiesis; Hematopoietic; Hematopoietic stem cells; Housing; Human; Human Development; Immune; Immunology; Immunophenotyping; In Vitro; Institutes; Investigation; Laboratories; Lead; Lesion; Libraries; Malignant Neoplasms; Malignant lymphoid neoplasm; Methylcellulose; MicroRNAs; Modeling; Molecular; Molecular Profiling; Molecular Target; Mus; Myeloid Leukemia; Oncogenes; Pathogenesis; Pathology; Pathway interactions; Patients; Pediatric Hematology/Oncology; Pharmaceutical Preparations; Phenotype; Play; Population; Principal Investigator; Proliferating; Property; Proteins; Proto-Oncogenes; Regenerative Medicine; Research; Research Personnel; Residencies; Resources; Retroviridae; Role; Sampling; Staging; Stem cells; System; Techniques; Testing; Therapeutic; Time; Tissues; Tort; Training; Transplantation; Triage; Tumor Suppressor Genes; Tumor Suppressor Proteins; Universities; Work; Xenograft Model; Xenograft procedure; base; c-myc Genes; cancer stem cell; carcinogenesis; career; daughter cell; design; effective therapy; granulocyte; improved; in vitro Assay; in vivo; innovation; insight; knock-down; leukemia; leukemic stem cell; leukemogenesis; macrophage; member; mouse model; novel; overexpression; progenitor; prognostic; programs; research study; self-renewal; skills; stem; stem cell biology; stem cell population; tool; tumor; Accounting; Acute Myelocytic Leukemia; Adult; Anatomy; Antibody Therapy; Apoptosis; Biological Assay; Blast Cell; Bone Marrow Transplantation; Cancer Biology; Cell physiology; Cell surface; Cells; Chromosomal translocation; Chronic Myeloid Leukemia; Chronic Phase; Clinical; Commit; Communities; Comprehensive Cancer Center; Crowding; Culture Techniques; Data; Daughter; Development; Development Plans; Developmental Process; Diagnosis; Diagnostic; Disease; Engraftment; Environment; Epigenetic Process; Event; Exhibits; Experimental Pathology; Fellowship; Figs - dietary; Future; Gene Fusion; Gene Mutation; Gene Targeting; Genes; Genetic; Genome Stability; Goals; Hematopathology; Hematopoiesis; Hematopoietic; Hematopoietic stem cells; Housing; Human; Human Development; Immune; Immunology; Immunophenotyping; In Vitro; Institutes; Investigation; Laboratories; Lead; Lesion; Libraries; Malignant Neoplasms; Malignant lymphoid neoplasm; Methylcellulose; MicroRNAs; Modeling; Molecular; Molecular Profiling; Molecular Target; Mus; Myeloid Leukemia; Oncogenes; Pathogenesis; Pathology; Pathway interactions; Patients; Pediatric Hematology/Oncology; Pharmaceutical Preparations; Phenotype; Play; Population; Principal Investigator; Proliferating; Property; Proteins; Proto-Oncogenes; Regenerative Medicine; Research; Research Personnel; Residencies; Resources; Retroviridae; Role; Sampling; Staging; Stem cells; System; Techniques; Testing; Therapeutic; Time; Tissues; Tort; Training; Transplantation; Triage; Tumor Suppressor Genes; Tumor Suppressor Proteins; Universities; Work; Xenograft Model; Xenograft procedure; base; c-myc Genes; cancer stem cell; carcinogenesis; career; daughter cell; design; effective therapy; granulocyte; improved; in vitro Assay; in vivo; innovation; insight; knock-down; leukemia; leukemic stem cell; leukemogenesis; macrophage; member; mouse model; novel; overexpression; progenitor; prognostic; programs; research study; self-renewal; skills; stem; stem cell biology; stem cell population; tool; tumor

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.

描述（由申请人提供）：这项5年的宣传描述了一项实验病理事业发展的综合计划。首席研究人员在斯坦福大学完成了解剖病理学和血液病理学奖学金培训，并在过去的两年中磨练了他作为诊断性血管病医生的技能，同时花费了大部分时间发展他的技术和智力技能，使他能够成为一名独立研究员。 拟议的工作将在欧文·韦斯曼（Irving L. Weissman）的实验室中进行，欧文·韦斯曼（Irving L.鉴于智力和技术资源的广度和深度，魏斯曼博士的实验室代表了一个独特的环境，不仅旨在允许高度创造性和创新的项目实现，而且还培训未来的独立研究人员。 鉴于越来越多的证据表明microRNA在人类癌症的发展中发挥作用，该提议代表了对人急性髓样白血病（AML）发病机理的及时研究。与常规的癌症生物学研究不同，拟议的研究将重点放在AML的肿瘤发射或干细胞上。由于白血病干细胞（LSC）具有独特的特性，包括在异种移植模型中启动肿瘤，自我更新和概括疾病的能力，因此我们必须了解AML LSC生物学特性的分子基础。由于与主要人类样本一起工作的独特实验挑战，因此已经并且将继续投入大量时间来开发改进的模型来研究microRNAS在人类AML中的作用。 斯坦福大学干细胞生物学和再生医学研究所是这些研究的理想环境。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计划与其他部门的成员合作，包括斯坦福大学综合癌症中心，免疫学计划等。鉴于斯坦福大学的临床部门（成人和小儿血液学/肿瘤学，骨髓移植，血液病理学）的强度，有重要的组织进入以及与临床同事合作的机会。