CAREER: The molecular mechanisms governing fate decisions of human embryonic stem cells

该职业计划旨在将PI在人类胚胎干细胞（hESCs）方面的研究与创建新的本科课程、培养下一代科学家、社区外展以及与研究界和公众分享hESCs的知识和最新信息相结合。智力优势：hESCs已被公认为是用于治疗目的的分化人类细胞的来源，但其在理解人类发育和许多基本生物学问题方面的巨大潜力却被严重低估和探索不足。本研究的目标是探索hESCs作为一个发育系统的潜力，并定义控制hESCs命运决定的分子程序。基于基因组学和化学筛选的发现，PI建议采用多学科结合的方法，包括细胞生物学、基因组学、蛋白质组学和化学遗传学，来破译控制多能性和分化的信号网络。这项研究如果成功，将大大提高我们对早期人类发育分子基础的认识。此外，本研究的结果将有助于全面了解细胞的生长、分化和可塑性。更广泛的影响：hESCs的研究引起了广泛的兴趣和公众的争论。随着科学技术的不断进步，围绕这些发展的伦理观点也在不断发展。缺乏对hESC的整体和技术理解严重阻碍了hESC的研究。PI计划在倡导、教育和探索科学和伦理问题方面发挥积极作用。在教育和推广工作上投入一些时间将有助于改变人们对hESCs的理解，减轻他们的担忧，并激发他们的兴趣。这反过来又将对这一新兴的、有前途的研究领域的发展产生非常积极的影响。

This CAREER proposal aims to integrate the PI's research in human embryonic stem cells (hESCs) with the creation a new undergraduate course, training of next generation of scientists, community outreach and sharing knowledge and current information of hESCs with the research community and the general public.Intellectual Merit: hESCs have been well recognized as a source for derivation of differentiated human cells for therapeutic purposes, but their enormous potential for understanding human development and many fundamental biological questions have been severely under-appreciated and under-explored. The goal of the proposed research is to explore the potential of hESCs as a developmental system and define the molecular programs that govern fate decisions in hESCs. Based on the findings from genomic and chemical screens, the PI proposes to apply a combined multidisciplinary approach including cell biology, genomics, proteomics and chemical genetics to decipher the signaling networks underlying the control of pluripotency and differentiation. The proposed research, if successful, will significantly improve our knowledge of the molecular basis of early human development. In addition, the results from this proposed research will contribute to the overall knowledge of cell growth, differentiation and plasticity.Broader Impacts: Research on hESCs has generated much interest and public debate. As science and technology continue to advance, so do ethical viewpoints surrounding these developments. The lack of overall and technological understanding of hESCs has severely hindered hESC studies. The PI plans to play an active role in advocating, educating and exploring the issues, both scientifically and ethically. The investment of some time in educational and outreach efforts will help to transform people's understanding of hESCs, alleviate their concerns, and stimulate their interest. This in turn will impact very positively on the advancement of this nascent and promising research field.