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.
摘要
造血干细胞(HSC)维持成人的血液和免疫系统的整个生命周期
一个有机体。虽然HSC移植在临床上用于白血病患者的治愈性治疗,
淋巴瘤和免疫系统疾病,HSC移植的成功率差异很大,有些患者
由于HSC植入效率低下而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聚糖Syndecan-2如何调节HSC的维持和再生。
目的1将利用新产生的组织特异性基因敲除小鼠来分析Syndecan-2在细胞凋亡中的作用。
调节HSC植入,同时对Syndecan的分子基序进行结构-功能分析,
2在介导植活和生态位再生中的作用。目的2将分析Syndecan-2在调节细胞凋亡中的作用。
联合应用放射损伤和骨髓抑制在HSC体内模型中从应激中恢复造血
自我更新这些实验将证明多配体蛋白聚糖-2在介导HSC维持中的作用,
再生,提供基础知识,使进一步研究蛋白多糖如何调节HSC。
从完成拟议目标中获得的知识预计将具有广泛的潜力
作为治疗方案的一部分,
各种癌症、免疫性疾病、白血病和贫血以及公共卫生的治疗价值
治疗意外辐射暴露患者的观点。
我的职业目标是成为一个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,研究蛋白聚糖如何调节HSC和HSC微环境
在体内平衡和压力下。为实现这些目标,拟议项目在以下方面开展了培训:
模拟HSC从损伤中恢复,同时扩展我对糖生物学和生长因子信号传导的知识。
在这个奖项下,我将继续与约翰·丘特博士(加州大学洛杉矶分校)的指导下进行拟议的培训,
在HSC和生态位再生的转化建模方面有丰富的经验,同时得到咨询公司的支持。
在干细胞生物学、生长因子信号和蛋白聚糖生物学方面具有专长的委员会。作为
作为博士后,我将在国际会议上和我的指导委员会上介绍我的工作,
由该领域的专家组成。作为初级教员,我将接受实验室管理/领导方面的培训,
写作、谈判和指导,帮助我领导一个成功的研究团队。该项目将允许
我过渡到一个独立的研究职位,同时发展我在HSC生物学的技能。加州大学洛杉矶分校
一流的研究设施,专业的发展资源和行政支持,这将提供
必要的基础设施,以支持我的研究和职业发展作为一个指导博士后研究员
最终,我向独立的过渡。
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)
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Christina Marie Termini其他文献
Inventories invite independence
库存有助于实现自主。
- DOI:
10.1016/j.tibs.2024.11.003 - 发表时间:
2025-01-01 - 期刊:
- 影响因子:11.000
- 作者:
Kayleigh Robichaux;Taylor Billings;Christina Marie Termini - 通讯作者:
Christina Marie Termini
Christina Marie Termini的其他文献
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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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