Molecular Mechanisms of Blood Cell Transfusion

血细胞输注的分子机制

• 批准号: 8289606
• 负责人: Leslie Eric Silberstein
• 金额: $ 205.14万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8289606
• 关键词: Animals; Blood; Blood Cells; Blood Transfusion; Bone Marrow; Cell Therapy; Cells; Clinical; Communicable Diseases; Development; Discipline; Engraftment; Event; Faculty; Flow Cytometry; Focal Adhesion Kinase 1; Goals; Hematopoietic; Hematopoietic Stem Cell Transplantation; Hematopoietic stem cells; Homeostasis; Immunotherapy; Investigation; Joints; Laboratories; Lead; Malignant Neoplasms; Medicine; Molecular; Organ; Pathway interactions; Performance; Population; Principal Investigator; Progenitor Cell Engraftment; Role; Serological; Services; Signal Transduction; Stem cells; Transcriptional Regulation; Transfusion; Translating; Transplantation; Zinc Fingers; granulocyte; improved; innovation; insight; medical schools; peripheral blood; programs; stem; therapy development; transcription factor

PROJECT SUMMARY (See instructions): Transfusion medicine has evolved from a laboratory-centered service with a focus on the serological investigation of blood to a clinical discipline that involves cellular therapies for hematopoietic stem cell transplantation and immunotherapy for infectious diseases and cancer. One of the greatest challenges of modern transfusion medicine is to improve the efficacy of cell therapies. We propose herein an extensive collaborative program entitled "Molecular mechanisms of blood cell transfusion". The long-term goal Of this new program is to better understand the pathways by which transfused bone marrow or peripheral blood derived cells migrate to their intended organs/ microenvironments and carry out their distinct functions. Our hypothesis is that the efficacy of blood transfusion can be improved via rnpdulating these pathways. The proposed program will consist of three projects and three cores. The principal investigator, project leaders and core leaders are all faculty of the Joint Program in Transfusion Medicine at Harvard Medical School. Project 1, Dr. Leslie Silberstein will study niche-induced signaling in hematopoietic stem/progenitor cell (HSC/P) transplantation. The goals of this project are to define Focal Adhesion Kinase (FAK) as a regulator of interactions between HSC/P and BM niche components, which are essential for HSC homeostasis and engraftment. Project 2, Dr. Li Chai will investigate transcriptional regulation in hematopoietic differentiation. This project will focus on the role of SALL4, a newly identified zinc-finger transcription factor, in differentiation of hematopoietic stem cells, which is a key factor for further development of ex vivo expansion of HSC and HPC cell populations and optimization of stem and progenitor cell engraftment. Project 3, Dr. Hongbo Luo will study ceil signaling in granulocyte transfusion. The ultimate goal is to identify cellular and molecular events that can improve granulocyte performance after transfusion. The three supporting cores are: Administrative Core, Animal Core, and a Flow Cytometry Core. Collectively, this program will yield significant insight and information that will directly translate into optimization of existing cell therapies and development of new ones.

项目总结（见说明）： 输血医学已经从以实验室为中心的服务，重点是血液的血清学研究，发展成为一门临床学科，涉及造血干细胞移植的细胞治疗和传染病和癌症的免疫治疗。现代输血医学的最大挑战之一是提高细胞疗法的疗效。我们在此提出了一个广泛的合作计划，题为“血液细胞输血的分子机制”。这项新计划的长期目标是更好地了解骨髓或外周血来源的细胞迁移到其预期器官/微环境并执行其独特功能的途径。我们的假设是，通过调节这些途径可以提高输血的疗效。拟议的计划将由三个项目和三个核心组成。主要研究者、项目负责人和核心领导人都是哈佛医学院输血医学联合项目的教员。项目1，Leslie Silberstein博士将研究造血干细胞/祖细胞（HSC/P）移植中的利基诱导信号传导。本项目的目标是将粘着斑激酶（FAK）定义为HSC/P和BM生态位组分之间相互作用的调节剂，这对HSC稳态和植入至关重要。项目二，柴力博士将研究造血分化中的转录调控。本项目将重点研究新发现的锌指转录因子SALL 4在造血干细胞分化中的作用，这是进一步开发HSC和HPC细胞群体外扩增和优化干细胞和祖细胞植入的关键因素。项目3，罗洪波博士将研究粒细胞输注中的细胞信号传导。最终目标是确定可以改善输血后粒细胞性能的细胞和分子事件。三个支持核心是：管理核心、动物核心和流式细胞术核心。总的来说，该计划将产生重要的见解和信息，这些见解和信息将直接转化为现有细胞疗法的优化和新疗法的开发。