Molecular Mechanismcs of Blood Cell Transfusion

输血医学已经从以实验室为中心的服务演变为专注于血清学的服务 对涉及造血干细胞细胞治疗的临床学科的血液调查 传染病和癌症的移植和免疫治疗。最大的挑战之一是 现代输血医学是为了提高细胞疗法的疗效。我们在此提议广泛的 题为“血细胞输注的分子机制”的合作项目。这样做的长期目标是 新的计划是更好地了解输注骨髓或外周血的途径 衍生细胞迁移到其预定的器官/微环境，并执行其不同的功能。我们的 假说是，通过调节这些途径可以提高输血的效率。这个 拟议的计划将包括三个项目和三个核心。首席调查员、项目负责人 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博士将研究在造血干/祖细胞中利基诱导的信号传递 (HSC/P)移植。该项目的目标是将焦点黏附蛋白激酶(FAK)定义为一种调节因子 HSC/P和BM生态位成分之间的相互作用，这是HSC动态平衡和 嫁接。项目2，李柴博士将研究造血分化过程中的转录调控。 本项目将重点研究新发现的锌指转录因子SALL4在分化过程中的作用 这是进一步发展HSC和HPC细胞群体体外扩增以及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。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： 行政核心、动物核心和流式细胞术核心。总而言之，该计划将产生重要的见解和信息，将直接转化为现有细胞疗法的优化和新疗法的开发。

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 factorforfurtherdevelopment 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.