Engineering Embryonic Stem Cell Differentiation into Hepatocytes

描述(由申请人提供)： 这份研究职业奖提案描述了一项为期五年的培训计划，旨在发展作为医生-科学家和生物医学工程师的学术生涯。首席研究员(PI)接受过内科和工程师培训，在迈阿密大学/杰克逊纪念医院完成了内科住院医师资格，并在马萨诸塞州综合医院(MGH)/哈佛医学院获得了研究奖学金。他的职业目标是建立一个专注于肝脏组织工程和生物人工肝(BAL)开发的尖端研究项目。 通过讲授课程和指导计划，PI将专注于胚胎干细胞生物学的研究。马丁·雅穆什博士是一位公认的组织工程和新陈代谢工程专家，他将在整个项目过程中担任公共图书馆的导师。他是麻省理工学院外科教授和医学工程中心主任。他曾指导过许多生物医学工程方面的博士后研究员和研究生。麻省理工学院医学系副教授、干细胞生物学权威大卫·斯卡登博士将担任该项目的共同导师。他曾指导过许多博士后研究员和医学生。由杰出的医生、科学家和工程师组成的研究咨询委员会将为PI提供科学和职业指导。 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。其具体目标是：(1)开发用于高通量鉴定胚胎干细胞向肝细胞分化的微流控生物反应器；(2)利用固定化和可溶性因子调节胚胎干细胞向成熟肝细胞的分化；(3)利用代谢工程原理鉴定分化的细胞群并优化其器官特异性功能的表达。这些研究将提供基础知识和技术，使PI能够为BAL设备开发稳定的肝细胞来源。 麻省理工学院外科的医学工程中心和哈佛医学院社区提供了一个良好的环境来促进PI的职业生涯。杰出的教员、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提供追求和启动其职业目标所需的一切。

DESCRIPTION (provided by applicant): This Research Career Award proposal describes a five year training program for the development of an academic career as a physician-scientist and biomedical engineer. The principal investigator (PI), with training as a physician and engineer, completed residency in Internal Medicine at University of Miami/Jackson Memorial Hospital and a research fellowship at Massachusetts General Hospital (MGH)/Harvard Medical School. His career goal is to establish a cutting edge research program focusing on hepatic tissue engineering and bioartificial liver (BAL) development. Through a program of didactic coursework and mentorship, the PI will focus his research efforts on embryonic stem cell biology. Dr. Martin Yarmush, a recognized expert in tissue engineering and metabolic engineering, will serve as the Pl's mentor throughout the course of this project. He is Professor in the Department of Surgery at MGH and the director of the Center for Engineering in Medicine. He has supervised numerous postdoctoral fellows and graduate students in biomedical engineering. Dr. David Scadden, Associate Professor in the Department of Medicine at MGH, and an authority on stem cell biology, will serve as a co-mentor on this project. He has supervised numerous postdoctoral fellows and medical students. A research advisory committee, composed of distinguished physicians, scientists, and engineers, will provide scientific and career guidance to the PI. 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 specific aims are: (1) To develop a microfluidic bioreactor for high throughput characterization of embryonic stem cell differentiation into hepatocytes; (2) To regulate embryonic stem cell differentiation into mature hepatocytes using immobilized and soluble factors; (3) To characterize the differentiated cell populations and optimize their expression of organ specific functions using principles of metabolic engineering. These studies will provide the basic knowledge and technologies enabling the PI to develop a steady source of hepatocytes for BAL devices. The Center for Engineering in Medicine in the Department of Surgery at MGH, and the Harvard Medical School community provide an excellent environment in which to foster the career of the PI. The distinguished faculty, interdisciplinary environment, well equipped core facilities, and extensive collaborative interactions will provide the PI with everything necessary to pursue and launch his career goals.