Comparative Biology of Tissue Repair, Regeneration and Aging

总体项目摘要 在人类和其他哺乳动物中，受损和丢失组织的再生是有限的。然而，鲁棒 再生是许多不同的无脊椎动物和低等脊椎动物的常态。COBRE第一阶段， 组织修复、再生和衰老的比较生物学，在建立和 凯瑟琳·W戴维斯再生生物学和医学中心（Davis Center for Regenerative Biology and Medicine） 生物实验室（MDIBL）和显着改善该机构的研究环境。戴维斯 该中心成立的指导原则是，研究不同的动物模型将导致一个详细的， 组织和器官再生的细胞和分子机制的预测性理解，以及 了解为什么这些过程在大多数人体组织中活性很差，以及为什么它们随着时间的推移而下降。 疾病和衰老。这反过来又会为再生医学的发展奠定合理的基础 治疗，特别是能够刺激组织再生和减缓组织再生的小分子候选药物， 或逆转患者的衰老引起的退行性变化。 COBRE第一阶段支持了四名职业生涯早期的项目领导人和一名职业生涯中期的项目领导人。所有 五名项目领导人在独立赠款支持下从第一阶段毕业。的平均时间 四名早期职业生涯项目负责人的毕业时间为2.8年。第一阶段项目负责人还实现了 其他多项成功，包括发表重要的同行评审论文， 财产，收到基金会和R21赠款和重要的同行认可。其他值得注意的成就 包括MSI-1436的进一步开发和专利，MSI-1436是已知的唯一一种刺激 心脏病发作后成年哺乳动物心脏的再生，发现两种小分子 有可能逆转化疗引起的周围神经损伤， 模型和研究工具，并形成一个不断增长的IDEA计划/缅因州州政府合作伙伴关系， 允许MDIBL获得300万美元的选民批准的国家债券资金，以扩大研究基础设施。 COBRE二期将继续支持戴维斯中心的成长和发展， 建立一个自我维持的调查员临界质量。三位新的早期科学家，萨姆·贝克博士， James Godwin和Jarod Rollins被聘为第二阶段项目负责人。招募第四名 戴维斯中心的教员正在进行中。第二阶段项目负责人的研究计划是高度 与戴维斯中心协同并为戴维斯中心带来新的科学专长。基本服务和资源将 通过继续比较研究，向项目负责人和更大的科学界提供 功能基因组学核心和比较动物模型核心。COBRE第二阶段将大大提高 戴维斯中心和MDIBL的发展，这反过来又将有助于继续加强 缅因州医学研究环境。

OVERALL PROJECT SUMMARY Regeneration of damaged and lost tissues is limited in humans and other mammals. However, robust regeneration is the norm for numerous diverse invertebrates and lower vertebrates. COBRE Phase I, Comparative Biology of Tissue Repair, Regeneration and Aging, played a central role in establishing and growing the Kathryn W. Davis Center for Regenerative Biology and Medicine (Davis Center) at the MDI Biological Laboratory (MDIBL) and in dramatically improving the institution’s research environment. The Davis Center was founded on the guiding principle that studying diverse animal models would lead to a detailed and predictive understanding of the cellular and molecular mechanisms of tissue and organ regeneration, and an understanding of why these processes are poorly active in most human tissues and of why they decline with disease and aging. This in turn would lead to a rational foundation for development of regenerative medicine therapies, particularly small molecule drug candidates capable of stimulating tissue regeneration and slowing or reversing aging-induced degenerative changes in patients. COBRE Phase I supported four early-career Project Leaders and one mid-career Project Leader. All five Project Leaders graduated from Phase I with independent grant support. The average time for graduation of the four early-career Project Leaders was 2.8 years. Phase I Project Leaders also achieved multiple other successes including publication of significant peer-reviewed papers, creation of intellectual property, receipt of foundation and R21 grants and significant peer recognition. Other noteworthy successes include further development and patenting of MSI-1436, the only small molecule known to stimulate regeneration of the adult mammalian heart following a heart attack, discovery of two small molecules with potential to reverse chemotherapy-induced peripheral nerve damage, development of new disease models and research tools, and formation of a growing IDeA program/Maine state government partnership that allowed MDIBL to obtain $3M in voter-approved state bond funding to expand research infrastructure. COBRE Phase II will continue to support the growth and development of the Davis Center in order to establish a self-sustaining critical mass of investigators. Three new early-career scientists, Drs. Sam Beck, James Godwin and Jarod Rollins, have been recruited as Phase II Project Leaders. Recruitment of a fourth Davis Center faculty member is underway. Research programs of Phase II Project Leaders are highly synergistic with and bring new scientific expertise to the Davis Center. Essential services and resources will be provided to the Project Leaders and larger scientific community by continuation of the Comparative Functional Genomics Core and Comparative Animal Models Core. COBRE Phase II will greatly enhance the development of the Davis Center and MDIBL, which in turn will contribute to the continued enhancement of the biomedical research environment in Maine.