Stem Cells and Aging

干细胞与衰老

• 批准号: 9356954
• 负责人: PETER J. QUESENBERRY
• 金额: $ 203.96万
• 依托单位: RHODE ISLAND HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9356954
• 关键词: Achievement; Advisory Committees; Aging; American; American Society of Hematology; Americas; Applications Grants; Area; Attention; Biology; Bone Marrow; Cell Aging; Cell physiology; Cells; Centers of Research Excellence; Central Nervous System Diseases; Chromatin; Collaborations; Complement; Development; Disease; Doctor of Philosophy; Educational workshop; Elements; Ensure; Evolution; Extramural Activities; FOXO3A gene; Faculty; Fibrosis; Focus Groups; Fostering; Foundations; Funding; Gerontology; Goals; Grant; Growth; Hematopoiesis; Hematopoietic; Hematopoietic stem cells; Hospitals; Individual; Institutes; International; Medical; Mentors; Myelogenous; Neoplasms; Phase; Pilot Projects; Program Research Project Grants; Proteins; Publications; Pulmonary Hypertension; Recording of previous events; Recruitment Activity; Regulation; Research; Research Personnel; Rhode Island; Role; Science; Scientist; Societies; Stem Cell Development; Stem cells; System; Talents; United States National Institutes of Health; Universities; Work; aged; career; career development; design; experience; extracellular vesicles; health economics; in vivo; interest; leukemia/lymphoma; meetings; member; mid-career faculty; multidisciplinary; nerve stem cell; oncology; professor; programs; reconstitution; relating to nervous system; senescence; success; symposium

Overall Summary/Abstract This Phase II COBRE application entitled “Stem Cells and Aging” focuses on neural and hematopoietic stem cells, their microenvironments and the impact of aging, fibrosis, and senescence on their regulation and evolution to diseases of the central nervous system and bone marrow. The COBRE continues to be led by Dr. Peter Quesenberry, but now adds Dr. John Sedivy as Associate Director Both have a long history of funded research in areas relevant to the projects in this proposal. The mentors are all outstanding and experienced investigators with significant mentoring experience and specific expertise for their mentees. Two of our previous project leaders are now mentors. The EAC consists of 4 excellent scientists who were on the last EAC and one new member focused on aging and chromatin biology. There are 4 related projects and 2 Cores. We will build on the success of our Phase I COBRE in which we saw 5 of our 6 investigators progress in their careers and 2 individuals obtained R01 funding (3 R01s), one significant DOD funding, one Leukemia /Lymphoma Society support and one other K08 support. Total extramural support obtained by our fundees (not counting COBRE dollars) for all years was $11,283,095 and total publications were 134. We plan to employ enhanced metrics to support talented investigators and sculpt their projects so that they are competitive for garnering independent NIH support. The individual projects are 1.) Patrycja Dubielecka PhD on the role of Abelson interactive protein-1 and its effect on the microenvironment in the development of myeloid neoplasia with aging, 2.) Olin Liang PhD. on the role of aged microenvironment in normal hematopoiesis, defining the critical niche cells and the role of SHIP inhibition in vivo in reconstitution of aged and preleukemic microenvironment, 3.) Jill Kreiling PhD on the study of cellular senescence and role of retrotransposable elements, and 4.) Ashley Webb PhD to determine whether changes in the FOXO3 network underlies decline of neural stem cell function with aging. The success of our PHASE I COBRE derives from our attention to mentoring junior investigators but we will enhance this with new groups focused on Academic Advancement and Promotion and on Collaborative Grants. We will maintain our approach where we insist that our junior investigators participate in weekly meetings where we rotate from investigator to investigator in terms of keeping track of progress of their individual projects. All investigators have benefited from a close relationship with their mentors, and these will continue. Our goal here is the sequential development of successful R01 grant applications. We also realize that the growth of our investigators ultimately depends upon their ability to successfully complete academic milestones necessary for promotion, retention and eventual tenure. All of our Phase II project PIs are Assistant Professors, thus their promotion to Associate Professor will require meeting Brown milestones and as part of our Brown mentoring activities we will ensure that these milestones are met. Our long-term goal will be the development of an Institute focused on stem cells and aging.

摘要/Abstract 这第二阶段COBRE申请题为“干细胞和衰老”的重点是神经和造血干细胞 细胞，它们的微环境以及衰老，纤维化和衰老对其调节的影响， 发展为中枢神经系统和骨髓疾病。COBRE继续由博士领导。 彼得Quesenberry，但现在增加了博士约翰Sedivy作为副主任都有悠久的历史，资助 与本建议书项目有关的领域的研究。导师们都很优秀，经验丰富 调查员具有丰富的辅导经验和对学员的具体专门知识。我们的两 以前的项目领导人现在是导师。EAC由4位优秀的科学家组成，他们在最后一次 EAC和一名新成员专注于衰老和染色质生物学。有4个相关项目和2个核心。 我们将在第一阶段COBRE的成功基础上再接再厉，在第一阶段，我们看到6名研究人员中有5名在其 职业和2个人获得R 01资金（3个R 01），一个重要的国防部资金，一个白血病 /淋巴瘤协会的支持和另一个K 08支持。我们的资助者获得的校外支持总额 (not计算COBRE美元）为11，283，095美元，出版物总数为134。我们计划 采用增强的指标来支持有才华的调查人员，并塑造他们的项目， 获得独立的NIH支持。个别项目为1.）Patrycja Dubielecka博士 Abelson相互作用蛋白-1在髓系细胞发育中的作用及其对微环境的影响 肿瘤与衰老，2.）Olin Liang博士老年微环境在正常造血中的作用， 确定关键的小生境细胞和SHIP抑制在体内老年和白血病前期细胞重建中的作用 微环境，3.）Jill Kreiling博士研究细胞衰老和逆转录转座因子的作用 元素，4）。阿什利韦伯博士确定FOXO 3网络的变化是否是 神经干细胞功能与衰老的关系我们第一阶段COBRE的成功源于我们对以下方面的关注： 指导初级研究人员，但我们将通过专注于学术进步的新团队加强这一点 以及合作赠款。我们将坚持我们的方法，我们坚持我们的初级 研究者参加每周一次的会议，在会议上，我们在研究者之间进行轮换， 跟踪其个别项目的进展情况。所有调查人员都受益于密切的关系 和他们的导师在一起，这些将继续下去。我们的目标是成功的R 01的顺序开发 补助金申请。我们也意识到，我们的调查人员的成长最终取决于他们的能力， 成功完成晋升、保留和最终任期所需的学术里程碑。我们所有的 第二阶段项目的主要研究员是助理教授，因此他们晋升为副教授需要与 布朗的里程碑，作为我们布朗指导活动的一部分，我们将确保这些里程碑得到满足。 我们的长期目标将是建立一个专注于干细胞和衰老的研究所。