Understanding Appendage Regeneration in Mice

描述（由申请人提供）：生物学中最大的谜团之一是某些动物如何在受到创伤后再生失去的身体部位。哺乳动物中组织再生的例子很少，非哺乳动物物种的组织再生研究由于缺乏分子工具而受到限制。本研究计划旨在阐明哺乳动物组织再生如何在基因定义的小鼠组织再生模型中展开。目标1将利用发育生物学、谱系追踪和条件小鼠遗传学来确定组织再生的细胞基础。目的2将确定在组织再生过程中特定蛋白在调节基因表达和染色质可及性中的作用。Aim #2将利用定量mRNA测序（RNA-Seq）和足迹染色质可及性（ATAC-Seq）的新技术。成功完成上述目标将极大地推进我们对哺乳动物组织再生机制的理解，这一知识可能为如何触发人类组织再生提供见解，并影响再生医学的未来策略。该奖项将使首席研究员，一位受过皮肤科训练的内科科学家，接受皮肤生物学、发育生物学和基因组学方面的强化培训，并制定一个独立的研究计划。此外，梁博士将完成结构化的职业发展，包括教学课程、道德行为培训和实验室管理培训。斯坦福大学正在为他提供全面的制度支持、广泛的资源以及与该领域专家合作的机会。斯坦福大学皮肤学系在指导皮肤科医生和科学家担任独立职位方面有着良好的记录。该奖项将帮助梁博士过渡到全职学术终身职位，他将把90%的时间用于研究，10%用于临床活动。

DESCRIPTION (provided by applicant): One of the great mysteries in biology is how do certain animals regenerate lost body parts in response to trauma. Few examples of tissue regeneration exist in mammals, and studies of tissue regeneration in non- mammalian species are limited by a lack of molecular tools. This research plan aims to elucidate how mammalian tissue regeneration unfolds in a genetically defined mouse model of tissue regeneration. Aim #1 will determine the cellular basis of tissue regeneration utilizing developmental biology, lineage tracing, and conditional mouse genetics. Aim #2 will determine the role of a specific protein in regulating gene expression and chromatin accessibility during tissue regeneration. Aim #2 will utilize quantitative mRNA sequencing (RNA-Seq) and a new technique to footprint chromatin accessibility (ATAC-Seq). Successful completion of the proposed aims will greatly advance our understanding of how mammalian tissue regeneration unfolds, and this knowledge may offer insights on how to trigger tissue regeneration in humans and impact future strategies in regenerative medicine. This award will enable the principle investigator, a dermatology trained physician-scientist, to receive intensive training in skin biology, developmental biology, and genomics, and to develop an independent research program. Additionally, Dr. Leung will complete structured career development including didactic sessions, training in ethical conduct, and training in laboratory management. Stanford University is providing him full institutional support, extensive resources, and opportunity for collaborations with experts in the field. The Stanford Department of Dermatology has a strong track record in mentoring dermatology physician-scientists to independent positions. This award will help Dr. Leung transition to a full-time academic tenure-track position where he will spend 90% of his time on research and 10% on clinical activities.