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; 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.

总体摘要/摘要 此II期cobre应用标题为“干细胞和衰老”，重点是神经和造血茎 细胞，它们的微环境以及衰老，纤维化和感应对其调节的影响 演变为中枢神经系统和骨髓的疾病。毛刺继续由博士领导。 彼得·奎森伯里 在本提案中与项目相关的领域进行研究。导师都很出色，经验丰富 具有丰富的指导经验和特定专业知识的调查员。我们的两个 以前的项目负责人现在是导师。 EAC由4位出色的科学家组成 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。 我们将建立在我们阶段的成功基础上，我们看到我们的6名调查人员中有5个在他们的成功中进展 职业和2个人获得了R01资金（3 R01），一项重要的国防部资金，一个白血病 /淋巴瘤协会的支持和其他K08支持。我们的基金会获得的全部壁外支持 （不计算cobre美元）所有年份的价格为$ 11,283,095，总数为134。 员工增强了指标，以支持才华横溢的调查人员并雕刻他们的项目，以便他们是 获得独立NIH支持的竞争。各个项目是1.）Patrycja Dubielecka博士 阿伯森互动蛋白1的作用及其对微环境在髓样发展中的影响 衰老的肿瘤，2。）Olin Liang PhD。关于老化微环境在正常造血的作用， 定义临界小众细胞以及船体在体内抑制的作用 微环境，3。）吉尔·克雷林（Jill Kreiling Phd 元素和4。）Ashley Webb博士确定FOXO3网络中的变化是否构成下降 衰老的神经干细胞功能。我们阶段的成功cobre从我们的注意力引起了 指导初级调查人员，但我们将通过专注于学术进步的新小组来增强这一点 和晋升以及协作赠款。我们将保持我们坚持大三的方法 调查人员参加每周的会议，我们从研究员到调查员旋转 跟踪其各个项目的进度。所有调查人员都从亲密关系中受益 与他们的导师一起，这些将继续。我们的目标是成功R01的顺序发展 赠款申请。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，保留和事件任期所需的学术里程碑。我们全部 第二阶段PIS是助理教授，因此他们向副教授的晋升将需要开会 棕色的里程碑和作为我们棕色心理活动的一部分，我们将确保满足这些里程碑。 我们的长期目标将是一个专注于干细胞和衰老的研究所的发展。