Stem Cells and Aging

干细胞与衰老

• 批准号: 10210266
• 负责人: PETER J. QUESENBERRY
• 金额: $ 189.93万
• 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 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10210266
• 关键词: Achievement; Advisory Committees; Aging; American; American Society of Hematology; Americas; Applications Grants; Area; Attention; Biology; Bone Marrow; Cell Aging; 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; Oncology; Phase; Pilot Projects; Program Research Project Grants; Proteins; Publications; Pulmonary Hypertension; Recording of previous events; Regulation; Research; Research Personnel; Rhode Island; Role; Science; Scientist; Societies; Stem Cell Development; 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; professor; programs; reconstitution; recruit; relating to nervous system; senescence; stem cell aging; stem cell function; stem cells; 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.

总体摘要/摘要 这项名为“干细胞与衰老”的第二阶段Cobre应用侧重于神经和造血干细胞。 细胞、它们的微环境以及衰老、纤维化和衰老对它们的调节和 进化为中枢神经系统和骨髓疾病。科布雷博士继续领导着科布雷博士。 Peter Quesenberry，但现在增加了John Sedivy博士作为副主任，两人都有很长的资助历史 在与本提案中的项目相关的领域进行研究。导师都是杰出的，经验丰富的 调查人员具有丰富的指导经验和对其被指导者的专门知识。我们的两个人 以前的项目负责人现在是导师。EAC由4名优秀的科学家组成，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，在这一阶段中，我们看到6名调查人员中的5名在他们的 职业和2名个人获得了R01资金(3个R01)，1个重要的国防部资金，1个白血病 /淋巴瘤协会支持和另一个K08支持。我们的基金获得的全部校外支持 (不包括科布雷的美元)所有年份的收入为11,283,095美元，出版总数为134份。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，使他们 在获得独立的NIH支持方面具有竞争力。单个项目为1个。)帕特里加·杜比埃莱卡博士 Abelson相互作用蛋白-1在髓系发育中的作用及其对微环境的影响 随年龄增长的肿瘤，2.)梁奥林博士。论老年微环境在正常造血中的作用 确定关键的生态位细胞和体内SHIP抑制在老年和白血病前期重建中的作用 微环境，3。)Jill Kreling博士对细胞衰老及逆转座子作用的研究 元素，以及4.)Ashley Webb博士确定FOX03网络的变化是否是导致 神经干细胞的功能随着年龄的增长而变化。我们第一期Cobre的成功源于我们对 指导初级调查人员，但我们将通过关注学术进步的新小组来加强这一点 和推广以及关于合作助学金。我们将保持我们的做法，我们坚持我们的初级 调查人员参加每周一次的会议，在这些会议上，我们从一个调查员轮流到另一个调查员，就以下方面 跟踪各自项目的进展情况。所有调查人员都从密切的关系中受益 与他们的导师一起，这些将继续下去。我们在这里的目标是成功地开发R01 批准申请。我们还认识到，我们调查人员的成长最终取决于他们的能力 成功完成晋升、留任和最终终身教职所需的学术里程碑。我们所有的人 第二阶段项目主管是助理教授，因此他们晋升为副教授需要开会 棕色里程碑，作为我们布朗指导活动的一部分，我们将确保实现这些里程碑。 我们的长期目标将是发展一个专注于干细胞和衰老的研究所。