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

基本信息

批准号：
7302634
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
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-08-03 至 2012-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7302634
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 Cellular biology Chromosomal translocation Chronic Myeloid Leukemia Chronic Phase Clinical Commit Communities Comprehensive Cancer Center Crowding Culture Techniques Data Daughter Depth 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 Placement Play Polymerase Chain Reaction Population Principal Investigator Proliferating Property Protein Overexpression Proteins Proto-Oncogenes Regenerative Medicine Research Research Personnel Residencies Resources Retroviridae Role Sampling Staging Standards of Weights and Measures Stem cells System Techniques Testing Therapeutic Thinking 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 granulocyte improved in vitro Assay in vivo innovation insight knock-down leukemia leukemic stem cell leukemogenesis macrophage member mouse model novel progenitor prognostic programs research study self-renewal skills stem tool tumor

项目摘要

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）：这份为期 5 年的提案描述了实验病理学职业发展的综合计划。首席研究员在斯坦福大学完成了解剖病理学住院医师培训和血液病理学研究员培训，并在过去的两年里磨练了他作为诊断血液病理学家的技能，同时花费了大部分时间发展技术和智力技能，使他能够成为一名独立研究者。拟议的工作将在干细胞生物学、癌症干细胞生物学和造血领域国际公认的领导者 Irving L. Weissman 的实验室进行。鉴于智力和技术资源的广度和深度，韦斯曼博士的实验室代表了一个独特的环境，不仅旨在让高度创造性和创新的项目取得成果，而且还培养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着作用，该提案代表了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，拟议的研究将重点关注 AML 的肿瘤起始细胞或干细胞。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、自我更新和重现疾病的能力，因此我们必须了解 AML LSC 生物学特性的分子基础。由于与原始人类样本相关的独特实验挑战，我们已经并将继续投入大量时间来开发改进的模型来研究 microRNA 在人类 AML 中的作用。斯坦福干细胞生物学和再生医学研究所是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、免疫学项目等。鉴于斯坦福大学临床部门（成人和儿童血液学/肿瘤学、骨髓移植、血液病理学）的实力，有大量的组织接触机会以及与临床同事合作的机会。