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.

总体总结/摘要 这项名为“干细胞与衰老”的二期 COBRE 应用重点关注神经干细胞和造血干细胞 细胞及其微环境以及衰老、纤维化和衰老对其调节和作用的影响 演变为中枢神经系统和骨髓疾病。 COBRE 继续由 Dr. 领导。 Peter Quesenberry，但现在增加 John Sedivy 博士为副主任 两人都有悠久的资助历史 与本提案中的项目相关的领域的研究。导师们都很优秀，经验丰富 具有丰富指导经验和针对受训者的特定专业知识的研究人员。我们的两个 以前的项目负责人现在是导师。 EAC由4位最后的优秀科学家组成 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，我们看到 6 名研究人员中的 5 名在他们的研究方面取得了进展 职业生涯和 2 人获得了 R01 资助（3 个 R01）、一项重要的国防部资助、一名白血病资助 /淋巴瘤协会支持和另一项 K08 支持。我们的受资助者获得的外部支持总额 （不包括 COBRE 美元）所有年份的费用为 11,283,095 美元，出版物总数为 134 份。我们计划 采用增强的指标来支持有才华的研究人员并塑造他们的项目，以便他们 在获得独立的 NIH 支持方面具有竞争力。各个项目是 1.) Patrycja Dubielecka 博士 Abelson交互蛋白1在骨髓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。关于衰老微环境在正常造血中的作用， 定义关键的生态位细胞以及体内 SHIP 抑制在老年和白血病前期重建中的作用 微环境，3.) Jill Kreiling 博士，研究细胞衰老和逆转录转座子的作用 元素，以及 4.) Ashley Webb 博士，以确定 FOXO3 网络的变化是否是 神经干细胞的功能随衰老而变化。我们第一期 COBRE 的成功源于我们对 指导初级研究人员，但我们将通过专注于学术进步的新小组来加强这一点 和推广以及合作赠款。我们将坚持我们的方针，坚持让我们的初级员工 调查员参加每周一次的会议，我们在调查员之间轮流进行以下工作： 跟踪他们个人项目的进展。所有调查人员都受益于密切的关系 与他们的导师一起，这些将继续下去。我们的目标是成功的 R01 的后续开发 拨款申请。我们还意识到，调查人员的成长最终取决于他们的能力 成功完成晋升、保留和最终终身教职所需的学术里程碑。我们所有的 二期项目PI是助理教授，晋升副教授需要开会 布朗大学的里程碑，作为布朗大学指导活动的一部分，我们将确保实现这些里程碑。 我们的长期目标是建立一个专注于干细胞和衰老的研究所。