Training in Stem Cell Research

描述（由申请人提供）： K18干细胞研究职业提升奖的提案描述了一项为期一年的培训计划，该计划将允许主要研究者（PI）在其肝组织工程研究中适当使用干细胞。PI Martin Yarmush博士是一位医学博士生物工程师，在过去的15年里一直在开发生物人工肝支持系统的关键技术。生物人工肝支持系统开发中的一个关键问题是接种这些装置所需的大量分化肝细胞的有限可用性。作为解决这一问题的一种手段，PI已经倾向于干细胞工程，特别是专注于指导胚胎干细胞分化为肝细胞。经过一些经验性质的初步工作后，PI寻求在发育和干细胞生物学方面更有针对性的培训。通过教学课程，研讨会和研究计划，PI将专注于胚胎干细胞生物学。乔治博士。戴利，一个国际公认的干细胞专家将担任赞助商。PI将非常熟悉Daley博士实验室开发的与人类ES细胞自我更新和分化相关的许多技术，然后将其应用于将ES细胞定向为成熟肝细胞。本课题的研究重点是发展胚胎干细胞体外诱导分化成肝细胞的技术。为了开发该技术并更好地了解基础科学，将使用小鼠模型。该项目的总体目标有两个方面：（1）开发一种将患病成人肝细胞的时钟重置到祖细胞阶段的方法，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，我们希望产生一个克隆源的肝细胞，可用于各种应用的肝组织工程，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、麻省总医院医学工程中心、哈佛干细胞研究所及其杰出的教师、跨学科的环境、装备精良的核心设施和广泛的合作互动将为PI提供追求目标所需的一切。

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.