Training in Stem Cell Research

描述(由申请人提供)： 这份关于干细胞研究K18职业提升奖的提案描述了一项为期一年的培训计划，该计划将允许首席研究员(PI)在他的肝组织工程研究中适当地使用干细胞。这位名为马丁·雅穆什博士的医学博士是一名生物工程师，在过去的15年里，他一直在开发生物人工肝支持系统的关键技术。发展生物人工肝支持系统的一个关键问题是有限的大量分化的肝细胞所需的种子这些设备。作为解决这一问题的一种手段，PI已经被干细胞工程所吸引，特别是专注于引导胚胎干细胞分化为肝细胞。在一些经验性质的初步工作之后，PI寻求在发育和干细胞生物学方面进行更有针对性的培训。通过教学课程、研讨会和研究计划，PI将把他的努力集中在胚胎干细胞生物学上。国际公认的干细胞专家乔治·Q·戴利博士将担任赞助商。PI将非常熟悉戴利博士的实验室开发的许多与人类ES细胞的自我更新和分化相关的技术，然后将它们应用于将ES细胞定向为成熟的肝细胞。这项建议的研究重点是开发从胚胎干细胞(ES)体外获得成年肝细胞的技术。为了开发这项技术，并更好地了解基本的基础科学，将使用老鼠模型。这个项目的总体目标有两个：(1)开发一种方法，将患病成人肝细胞的时钟重新设置为祖细胞阶段，以及(2)了解祖细胞在增殖和分化之间切换的分子机制，以便在分化的肝细胞中表达更高水平的肝脏特异性功能。通过这项工作，我们希望生产出一种克隆的肝细胞来源，可以用于肝组织工程的各种应用，包括药物筛选、毒理学和生物人工肝辅助装置。波士顿儿童医院、麻省理工学院医学工程中心、哈佛干细胞研究所及其杰出的教师、跨学科的环境、配备齐全的核心设施以及广泛的协作互动将为PI提供实现其目标所需的一切。

DESCRIPTION (provided by applicant): This proposal for a K18 Career Enhancement Award for Stem Cell Research describes a one year training program which will allow the principal investigator (PI) to appropriately use stem cells in his research on Hepatic Tissue Engineering. The PI, Dr. Martin Yarmush, is an MD PhD bioengineer who for the past 15 years has been developing critical technologies for bioartificial liver support systems. A critical issue in the development of bioartificial liver support systems is the limited availability of large numbers of differentiated hepatocytes necessary to seed these devices. As a means of addressing this problem, the PI has gravitated towards stem cell engineering, specifically focusing on directing embryonic stem cell differentiation into hepatocytes. After some initial work of an empirical nature, the PI seeks more focused training in developmental and stem cell biology. Through a program of didactic coursework, seminars and research, the PI will focus his efforts on embryonic stem cell biology. Dr. George Q. Daly, an internationally recognized stem cell expert will serve as the sponsor. The PI will become intimately familiar with many of the techniques that Dr. Daley's lab has developed related to self-renewal and differentiation of human ES cells, and then apply them to directing ES cells to mature hepatocytes. The research focus in this proposal is to develop techniques to derive adult hepatocytes from embryonic stem (ES) cells in vitro. For the purpose of developing the technology and gaining a better understanding of the underlying basic science, a mouse model will be used. The overall goals of this project are two-fold: (1) to develop an approach to reset the clock of diseased adult hepatocytes to a progenitor stage, and (2) to understand the molecular mechanisms of switching between proliferation and differentiation in progenitor cells, so that higher levels of liver-specific functions can be expressed in the differentiated hepatocytes. Through this work, we hope to produce a clonal source of hepatocytes which could be used in various applications of hepatic tissue engineering, including drug screening, toxicology, and bioartificial liver assist devices. The Childrens Hospital Boston, the Center for Engineering in Medicine at MGH, the Harvard Stem Cell Institute with its distinguished faculty, interdisciplinary environment, well equipped core facilities, and extensive collaborative interactions will provide the PI with everything necessary to pursue his goals.