Unraveling stem cell behaviors upon injury to the brain

揭示大脑损伤后干细胞的行为

基本信息

  • 批准号:
    9805837
  • 负责人:
  • 金额:
    $ 9.41万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-08-01 至 2021-07-31
  • 项目状态:
    已结题

项目摘要

Candidate: My overarching goal is to understand the molecular mechanism that regulate self-renewal and differentiation of neural stem cell during homeostasis, regeneration and in neoplasms. To achieve this goal, I am pursuing a career in stem cell biology, focusing on the brain. My graduate work focused on characterizing molecularly distinct stem cell populations in patient-derived brain tumors and understanding their roles in tumorigenesis. In order to gain in depth experience on studying how stem cell behaviors are regulated in vivo, I chose to join Dr. Alexandra Joyner’s laboratory to study developmental neurobiology and regeneration. Here, I study the function of stem cells during repair of the developing and adult cerebellum. The main purpose of this grant is to provide the skills and knowledge that I need to build my own independent research program. Environment: Dr. Joyner’s lab provides a stimulating environment for me to gain research and mentoring skills to launch my career as an independent investigator. Under her mentorship and with the help of my colleagues along with the supportive institutional environment, I will learn the most sophisticated mouse models and developmental biology techniques that are crucial to study stem cells in vivo. In addition to Dr. Joyner, my advisors and collaborators will provide necessary training in genomics/epigenomics approaches to supplement my required knowledge and training in order to establish a multidisciplinary research program. Research: Regeneration in the brain is limited. I submit that an understanding of the gene regulatory networks that regulate the plasticity of neural stem/progenitor populations and their ability to self-renew and differentiate is crucial for discovering how to stimulate the regenerative potential of the brain. Our lab recently discovered that the neonatal cerebellum has a surprisingly high regenerative potential as it can recover from ablation of at least two types of neurons, making it an excellent system to uncover molecular events required for successful regeneration. Upon depletion of granule cell precursors, a subpopulation of Nestin-expressing progenitors (NEPs) change their fate from glia to produce excitatory granule neurons in a Hedgehog (HH)-dependent manner. Furthermore, I found that rare NEP-like cells exist in the adult cerebellum, and HH signaling and injury synergize to expand the population. However, their regenerative yield is limited. The aim of this proposal is to identify the signaling pathways and gene regulatory networks that control the regenerative response of NEPs to injury in the newborn cerebellum and determine how it differs in the adult. I will combine mouse genetics and injury models with whole genome transcriptomic/epigenomic analyses to dissect and compare the gene expression profiles of individual NEPs in the normal and injured newborn and adult cerebellum. In vitro and in vivo stem cells assays will then identify signaling pathways that stimulate self-renewal and reprogramming during regeneration, and candidate pro-regenerative pathways will be tested for their ability to enhance repair. My findings will provide a basis for in vivo manipulation of stem cells to facilitate repair of the brain.
候选人:我的首要目标是了解调节 自我更新和分化的神经干细胞在稳态,再生和肿瘤。到 为了实现这一目标,我正在从事干细胞生物学方面的工作,重点是大脑。我的毕业论文集中在 关于表征患者源性脑肿瘤中分子上不同的干细胞群, 它们在肿瘤发生中的作用。为了深入研究干细胞的行为, 在体内调节,我选择加入亚历山德拉乔伊纳博士的实验室,研究发育神经生物学, 再生在这里,我研究了干细胞在发育和成人小脑修复过程中的功能。的 这个补助金的主要目的是提供我需要建立自己的独立的技能和知识 研究计划。环境:乔伊纳博士的实验室为我提供了一个激励的环境,以获得研究 和指导技能来开始我作为独立调查员的职业生涯。在她的指导下, 我的同事的帮助沿着与支持性的制度环境,我会学到最先进的 小鼠模型和发育生物学技术是研究体内干细胞的关键。除了 博士乔伊纳,我的顾问和合作者将提供必要的基因组学/表观基因组学方法的培训 补充我所需的知识和培训,以建立一个多学科的研究计划。 研究:大脑的再生是有限的。我认为对基因调控网络的理解 调节神经干/祖细胞群体的可塑性及其自我更新和分化的能力 对于发现如何刺激大脑的再生潜力至关重要。我们的实验室最近发现, 新生儿小脑具有令人惊讶的高再生潜力,因为它可以从至少 两种类型的神经元,使其成为一个很好的系统,以揭示成功的分子事件所需的 再生在耗尽颗粒细胞前体后,表达Nestin的祖细胞亚群 在Hedgehog(HH)依赖性神经元中,NEPs改变其命运,从胶质细胞产生兴奋性颗粒神经元。 方式此外,我发现在成人小脑中存在罕见的NEP样细胞,HH信号和损伤 协同作用来扩大人口。然而,它们的再生产量有限。这项建议的目的是 确定控制NEP再生反应的信号通路和基因调控网络, 新生儿小脑的损伤,并确定它在成人中的不同。我会将联合收割机小鼠遗传学和 通过全基因组转录组/表观基因组分析来剖析和比较基因的损伤模型 在正常和损伤的新生儿和成人小脑中单个NEPs的表达谱。体外和 然后,体内干细胞测定将鉴定刺激自我更新和重编程的信号通路, 将测试候选的促再生途径增强修复的能力。我 研究结果将为在体内操作干细胞以促进大脑修复提供基础。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Nermin Sumru Bayin其他文献

Nermin Sumru Bayin的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Nermin Sumru Bayin', 18)}}的其他基金

Unraveling stem cell behaviors upon injury to the brain
揭示大脑损伤后干细胞的行为
  • 批准号:
    9977283
  • 财政年份:
    2019
  • 资助金额:
    $ 9.41万
  • 项目类别:

相似海外基金

心房細動に対するPulsed Field Ablationの組織創傷治癒過程を明らかにする網羅的研究
阐明房颤脉冲场消融组织伤口愈合过程的综合研究
  • 批准号:
    24K11201
  • 财政年份:
    2024
  • 资助金额:
    $ 9.41万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Targeted ablation of cerebral atherosclerosis using supramolecular self-assembly
利用超分子自组装靶向消融脑动脉粥样硬化
  • 批准号:
    24K21101
  • 财政年份:
    2024
  • 资助金额:
    $ 9.41万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
遅延造影心臓MRIによる心房細動Ablation冷却効果の比較:28 vs. 31 mm Cryoballoon
使用延迟对比增强心脏 MRI 比较房颤消融冷却效果:28 毫米与 31 毫米 Cryoballoon
  • 批准号:
    24K11281
  • 财政年份:
    2024
  • 资助金额:
    $ 9.41万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
CAREER: Heat Penetration Depth and Direction Control with Closed-Loop Device for Precision Ablation
职业:利用闭环装置控制热穿透深度和方向,实现精确烧蚀
  • 批准号:
    2338890
  • 财政年份:
    2024
  • 资助金额:
    $ 9.41万
  • 项目类别:
    Continuing Grant
Collaborative Research: RUI: Frontal Ablation Processes on Lake-terminating Glaciers and their Role in Glacier Change
合作研究:RUI:湖终止冰川的锋面消融过程及其在冰川变化中的作用
  • 批准号:
    2334777
  • 财政年份:
    2024
  • 资助金额:
    $ 9.41万
  • 项目类别:
    Continuing Grant
Collaborative Research: RUI: Frontal Ablation Processes on Lake-terminating Glaciers and their Role in Glacier Change
合作研究:RUI:湖终止冰川的锋面消融过程及其在冰川变化中的作用
  • 批准号:
    2334775
  • 财政年份:
    2024
  • 资助金额:
    $ 9.41万
  • 项目类别:
    Continuing Grant
InSPACE-VT_Development and Validation of Virtual Pace Mapping to Guide Catheter Ablation of Ventricular Tachycardia
InSPACE-VT_虚拟起搏测绘的开发和验证以指导室性心动过速导管消融
  • 批准号:
    EP/Z001145/1
  • 财政年份:
    2024
  • 资助金额:
    $ 9.41万
  • 项目类别:
    Fellowship
Collaborative Research: RUI: Frontal Ablation Processes on Lake-terminating Glaciers and their Role in Glacier Change
合作研究:RUI:湖终止冰川的锋面消融过程及其在冰川变化中的作用
  • 批准号:
    2334776
  • 财政年份:
    2024
  • 资助金额:
    $ 9.41万
  • 项目类别:
    Continuing Grant
MRI: Acquisition of a Laser Ablation - Inductively Coupled Plasma - Triple Quadrupole - Mass Spectrometer (LA-ICP-QQQ-MS) System For Research and Education
MRI:获取用于研究和教育的激光烧蚀 - 电感耦合等离子体 - 三重四极杆 - 质谱仪 (LA-ICP-MS/MS) 系统
  • 批准号:
    2320040
  • 财政年份:
    2023
  • 资助金额:
    $ 9.41万
  • 项目类别:
    Standard Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了