The role of Syndecan-2 in hematopoietic stem cell maintenance and regeneration
Syndecan-2 在造血干细胞维持和再生中的作用
基本信息
- 批准号:10301621
- 负责人:
- 金额:$ 12.31万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-07-01 至 2022-04-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAdultAdvisory CommitteesAnemiaAwardBiological AssayBiologyBloodBlood VesselsCell CountCell MaintenanceCell ProliferationCellsCellular biologyChemotherapy and/or radiationClinicalDataDoseEndotheliumEngraftmentEquilibriumFacultyFoundationsGlycobiologyGoalsGrantGrowth FactorHematopoiesisHematopoieticHematopoietic Stem Cell TransplantationHematopoietic stem cellsHeparan Sulfate ProteoglycanHeparitin SulfateHomeostasisHumanImageImmune System DiseasesImmune systemImmunodeficient MouseIndividualInfrastructureInjuryInstitutionIntegral Membrane ProteinInternationalKnockout MiceKnowledgeLaboratoriesLeadLeadershipMalignant NeoplasmsMeasuresMediatingMediationMedicalMentorsMentorshipMicroscopyModelingMolecularMolecular AnalysisMusMutationMyelosuppressionNatural regenerationOrganismPainPatientsPhasePolysaccharidesPositioning AttributePostdoctoral FellowProcessProteoglycanPublic HealthRadiation InjuriesRadiation exposureRadiation therapyRecoveryRegulationResearchResource DevelopmentRoleSignal TransductionSourceStressStructureSurfaceTestingTherapeuticTissuesTrainingTransplantationTreatment ProtocolsUmbilical Cord BloodWorkWritingXenograft procedurebasebone marrow failure syndromecareercareer developmentcell growthcell regenerationcurative treatmentsdifferential expressioneducational atmosphereexhaustionexperienceexperimental studyfibroglycangenetic signaturehematopoietic stem cell nichehematopoietic stem cell quiescencehematopoietic stem cell self-renewalhematopoietic tissueimprovedin vivoin vivo Modelinjury recoveryleukemialeukemia/lymphomamutantpost-doctoral trainingpreservationprofessorprogramsradiation recoveryregeneration following injuryregenerativerepairedresearch and developmentresearch facilityself-renewalstem cell biologystem cell engraftmentstem cellssuccesssymposiumtranscriptome sequencingtranslational model
项目摘要
ABSTRACT
Hematopoietic stem cells (HSCs) maintain the adult blood and immune systems throughout the lifetime
of an organism. While HSC transplants are used clinically for the curative treatment of patients with leukemias,
lymphomas, and immune disorders, the success of HSC transplants varies considerably, with some patients
having to undergo multiple transplants due to inefficient HSC engraftment. The goal of the proposed project is
to identify how the heparan sulfate proteoglycan, Syndecan-2, regulates HSC maintenance and regeneration.
Aim 1 will utilize newly generated tissue-specific knockout mice to analyze the contribution of Syndecan-2 in
regulating HSC engraftment, while performing a structure-function analysis of the molecular motifs of Syndecan-
2 in mediating engraftment and niche regeneration. Aim 2 will analyze the role of Syndecan-2 in regulating
hematopoietic recovery from stress by combining radiation injury and myelosuppression in vivo models of HSC
self-renewal. These experiments will demonstrate the role of Syndecan-2 in mediating HSCs maintenance and
regeneration, providing foundational knowledge to enable further study of how proteoglycans regulate HSCs.
The knowledge procured from the completion of the proposed aims is expect to have broad potential
contributions to patients undergoing chemotherapy and radiation therapy as a part of their treatment regimen for
variety of cancers, immune diseases, leukemias and anemias and therapeutic value from a public health
standpoint for treating patients that experience accidental radiation exposure.
My career goals are to become an assistant professor at a top-tier academic research institution. I aim
to lead a research program that investigates how proteoglycans regulate HSCs and the HSC microenvironment
at homeostasis and during stress. To achieve these goals, the proposed project has embedded training in
modeling HSC recovery from injury, while expanding my knowledge of glycobiology and growth factor signaling.
Under this award, I will pursue the proposed training with the mentorship of Dr. John Chute (UCLA), who has
substantial experience in translational modeling of HSC and niche regeneration, while supported by an Advisory
Committee with expertise in stem cell biology, growth factor signaling and proteoglycan biology. As a
postdoctoral fellow, I will present my work at international conferences and to my mentoring committee, which
consists of experts in the field. As junior faculty, I will receive training in laboratory management/leadership, grant
writing, negotiation, and mentoring to help me lead a successful research team. The proposed project will allow
me to transition to an independent research position while developing my skillset in HSC biology. UCLA has
superb research facilities, professional development resources and administrative support, which will provide
the necessary infrastructure to support my research and career development as a mentored postdoctoral fellow
and ultimately, my transition to independence.
抽象的
造血干细胞 (HSC) 在一生中维持成人血液和免疫系统
一个有机体的。虽然 HSC 移植在临床上用于治疗白血病患者,
淋巴瘤和免疫疾病,造血干细胞移植的成功率差异很大,有些患者
由于造血干细胞移植效率低下,不得不进行多次移植。拟议项目的目标是
以确定硫酸乙酰肝素蛋白多糖 Syndecan-2 如何调节 HSC 的维持和再生。
目标 1 将利用新生成的组织特异性敲除小鼠来分析 Syndecan-2 在
调节 HSC 植入,同时对 Syndecan- 的分子基序进行结构功能分析
2 介导植入和生态位再生。目标 2 将分析 Syndecan-2 在调节中的作用
结合放射损伤和骨髓抑制 HSC 体内模型的应激造血恢复
自我更新。这些实验将证明 Syndecan-2 在介导 HSC 维持和
再生,为进一步研究蛋白聚糖如何调节 HSC 提供基础知识。
从完成拟议目标中获得的知识预计将具有广泛的潜力
对接受化疗和放疗作为治疗方案一部分的患者的贡献
多种癌症、免疫疾病、白血病和贫血以及公共卫生的治疗价值
治疗遭受意外辐射暴露的患者的立场。
我的职业目标是成为顶级学术研究机构的助理教授。我的目标
领导一项研究计划,调查蛋白多糖如何调节 HSC 和 HSC 微环境
在稳态和压力期间。为了实现这些目标,拟议项目将培训嵌入
模拟 HSC 从损伤中恢复的过程,同时扩展我对糖生物学和生长因子信号传导的了解。
根据该奖项,我将在 John Chute 博士(加州大学洛杉矶分校)的指导下进行拟议的培训,他曾
在 HSC 转化模型和利基再生方面拥有丰富的经验,同时得到咨询的支持
委员会拥有干细胞生物学、生长因子信号传导和蛋白聚糖生物学方面的专业知识。作为一个
作为博士后研究员,我将在国际会议上并向我的指导委员会展示我的工作,
由该领域的专家组成。作为初级教师,我将接受实验室管理/领导力、资助等方面的培训
写作、谈判和指导帮助我领导一个成功的研究团队。拟议的项目将允许
我过渡到独立研究职位,同时发展我在 HSC 生物学方面的技能。加州大学洛杉矶分校有
一流的研究设施、专业的发展资源和行政支持,这将为
作为指导博士后研究员,支持我的研究和职业发展所需的基础设施
最终,我过渡到独立。
项目成果
期刊论文数量(0)
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会议论文数量(0)
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Christina Marie Termini其他文献
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{{ truncateString('Christina Marie Termini', 18)}}的其他基金
The role of Syndecan-2 in hematopoietic stem cell maintenance and regeneration
Syndecan-2 在造血干细胞维持和再生中的作用
- 批准号:
10696158 - 财政年份:2022
- 资助金额:
$ 12.31万 - 项目类别:
The role of Syndecan-2 in hematopoietic stem cell maintenance and regeneration
Syndecan-2 在造血干细胞维持和再生中的作用
- 批准号:
10639822 - 财政年份:2022
- 资助金额:
$ 12.31万 - 项目类别:
Spatiotemporal Analysis of CD82-mediated Integrin Adhesion
CD82 介导的整合素粘附的时空分析
- 批准号:
8994175 - 财政年份:2014
- 资助金额:
$ 12.31万 - 项目类别:
Spatiotemporal Analysis of CD82-mediated Integrin Adhesion
CD82 介导的整合素粘附的时空分析
- 批准号:
9187854 - 财政年份:2014
- 资助金额:
$ 12.31万 - 项目类别:
Spatiotemporal Analysis of CD82-mediated Integrin Adhesion
CD82 介导的整合素粘附的时空分析
- 批准号:
8837877 - 财政年份:2014
- 资助金额:
$ 12.31万 - 项目类别:
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