Understanding Appendage Regeneration in Mice

了解小鼠附肢再生

• 批准号: 9414125
• 负责人: Thomas H. Leung
• 金额: $ 0.1万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9414125
• 关键词: Active Sites; Adult; Aging; Alpha Cell; Animals; Architecture; Automobile Driving; Award; Biological Assay; Biology; Blood Vessels; Body part; Cartilage; Cell Aging; Cell Cycle; Cell Cycle Arrest; Cell Lineage; Cells; Chromatin; Clinical; Collaborations; Complement; Cyclin-Dependent Kinase Inhibitor; DNA Repair; Data; Dermatologic; Dermatology; Developmental Biology; Ear; Enhancers; Ethics; Exhibits; Fluorescence-Activated Cell Sorting; Future; GADD45A gene; Gene Expression; Genetic; Genomics; Germ Layers; Hair; Harvest; Human; Invertebrates; Knockout Mice; Knowledge; Laboratories; Mammals; Measures; Mediating; Mediator of activation protein; Mentors; Messenger RNA; Modeling; Molecular; Molecular Biology; Multipotent Stem Cells; Mus; Natural regeneration; Organism; Pathway interactions; Physicians; Population; Positioning Attribute; Process; Proteins; Regenerative Medicine; Regulator Genes; Research; Research Personnel; Resources; Role; Salamander; Scientist; Site; Skin; Stem cells; Structure; TP53 gene; Techniques; Testing; Time; Tissues; Training; Translating; Transposase; Trauma; Undifferentiated; Universities; Work; appendage; blastema; career development; cell behavior; cell type; experimental study; healing; in vivo; induced pluripotent stem cell; insight; keratinocyte; limb regeneration; mouse model; multipotent cell; progenitor; programs; promoter; public health relevance; response; self-renewal; stem cell biology; tenure track; tissue regeneration; tool; transcriptome sequencing; wound

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.

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因创伤而再生失去的身体部位。哺乳动物中几乎没有组织再生的例子，并且非哺乳动物物种中组织再生的研究因缺乏分子工具而受到限制。该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确定组织再生的细胞基础。目标#2 将确定特定蛋白质在组织再生过程中调节基因表达和染色质可及性的作用。目标 #2 将利用定量 mRNA 测序 (RNA-Seq) 和足迹染色质可及性新技术 (ATAC-Seq)。成功完成所提出的目标将极大地增进我们对哺乳动物组织再生如何展开的理解，并且这些知识可能会为如何触发人类组织再生并影响再生医学的未来策略提供见解。该奖项将使首席研究员（一位受过皮肤病学培训的医师科学家）能够接受皮肤生物学、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。斯坦福大学为他提供全面的机构支持、广泛的资源以及与该领域专家合作的机会。斯坦福大学皮肤科在指导皮肤科医师科学家担任独立职位方面拥有良好的记录。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。