Determining the role of RALA and RALB in soft tissue sarcoma tumor growth and metastasis
确定 RALA 和 RALB 在软组织肉瘤肿瘤生长和转移中的作用
基本信息
- 批准号:9562031
- 负责人:
- 金额:$ 18.68万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-09-08 至 2020-08-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAdultAwardBiologicalBiological ModelsBreast cancer metastasisCancer Research ProjectCell LineCellsCessation of lifeClinicClinical PathwaysCollectionComplexComprehensive Cancer CenterCouplingDataDepartment of DefenseDiseaseDoctor of PhilosophyDrug TargetingEffectivenessElectronsExhibitsFacultyFoundationsFutureGene ExpressionGeneticGoalsGrantGrowthGuanosine Triphosphate PhosphohydrolasesIn VitroIncidenceLaboratoriesLungMalignant NeoplasmsMediatingMesenchymalMetastatic Neoplasm to the LungMetastatic toMicroscopicModelingMolecularMonomeric GTP-Binding ProteinsMusNational Cancer InstituteNeoplasm MetastasisNormal tissue morphologyNude MiceOhioOperative Surgical ProceduresPPP2R1B genePathway interactionsPatientsPhosphoproteinsPhosphoric Monoester HydrolasesPhosphorylationPlayPopulationPostdoctoral FellowProductionProtein IsoformsProtein Phosphatase 2A Regulatory Subunit PR53Protein phosphataseProteinsRALA geneRadiationResearchRoleSamplingSeedsSignal PathwaySoft tissue sarcomaStainsTestingTimeTissue SampleTissuesTrainingTumor Suppressor ProteinsUniversitiesWestern BlottingWorkXenograft procedureadvanced diseasebaseclinical applicationcohortcollaborative environmenteffective therapyexosomeexperimental studyextracellular vesiclesimprovedimproved outcomein vivoinhibitor/antagonistinnovationknock-downmalignant breast neoplasmmutantnoveloverexpressionprognosticprospectivetenure tracktherapeutic targetthree dimensional cell culturetumortumor growthtumor xenograft
项目摘要
Project Summary/Abstract
The K22 applicant, Dr. Steven Sizemore, obtained his Ph.D. in the laboratory of Dr. Graham Casey at
the Cleveland Clinic Foundation. His dissertation research focused on the fundamental mechanisms underlying
breast cancer metastasis. The candidate's training continued as a Department of Defense CDMRP Breast
Cancer Research Program supported postdoctoral fellow at Case Western Reserve University. This work
concentrated on identifying the molecular drivers of basal-like breast cancer. Currently, the candidate is a
Senior Research Associate at The Ohio State University James Comprehensive Cancer Center (OSUCCC).
The OSUCCC is ranked by the National Cancer Institute as an “exceptional” center and provides a vibrant and
collaborative environment in which the candidate has continued his training towards his long-term goal of
becoming tenure-track faculty at a Research I level university. The candidate's current work, on which this
proposal is based, centers on identifying the master regulators of soft tissue sarcoma (STS) metastasis and is
supported through a seed grant from the OSUCCC. STS is a diverse collection of cancers of mesenchymal
origin. The 5-year survival for patients with metastatic STS is a dismal 16% and there are few treatment
options for these patients. The long-term objective of this research is to address the urgent, unmet need for a
better understanding of the key molecular pathways that drive metastasis in STS and identify inhibitors of
these pathways to improve the treatment options for advanced STS. In pursuit of this objective, the candidate
identified the phosphatase subunit PPP2R1B as a suppressor of STS metastasis and one of its
phosphoprotein targets, RALA, as a putative actionable target for treating advanced STS. This proposal will
thoroughly test the hypothesis that RALA, and the closely related RALB, are important and targetable
drivers of STS tumor growth and metastasis that regulate STS progression, at least in part, by
controlling exosome production. Specific Aim 1: will test the functional requirement of the RAL isoforms and
their effectors in STS growth and metastasis in vitro and in vivo by coupling genetic silencing of these isoforms
with rescue experiments utilizing specific interaction-deficient RAL mutants. Specific Aim 2: will investigate the
essential requirement of the RAL isoforms and their effectors in exosome production by STS cells and
determine if these RAL-dependent exosomes control tumor growth and metastasis. Specific Aim 3: will utilize
STS cell lines and patient derived xenografts to determine the effectiveness of RAL-targeting inhibitors as
innovative treatments for STS. Successful completion of this proposal will identify an important actionable
target for improved treatment of advanced STS and identify a novel mechanism regulating cancer exosomes.
This award will allow the candidate the protected time required to transition his research from a breast cancer-
focus to the understudied field of STS metastasis and acquire the additional training required to become a
leader in the field of cancer-associated exosomes.
项目摘要/摘要
K22申请人Steven Sizemore博士在Graham Casey博士的实验室中获得了博士学位
他的论文研究着重于基本机制
乳腺癌转移。
癌症研究计划支持凯斯西部储备大学的博士后研究员。
集中于识别基底样乳腺癌的分子驱动因素。
俄亥俄州立大学詹姆斯综合癌症中心(OSUCCC)的高级研究助理。
OSUCCC由国家癌症研究所(National Cancer Institute)排名为“例外,并提供了充满活力的和
协作环境,候选人继续他的长期目标继续
成为I级大学的终身教师。
提案是基于IS的基于软组织肉瘤(STS)的主要调节剂的基于IS的基础。
通过OSUCCC的种子赠款支持。
起源于转移性ST的5年生存率是16%
粘贴的选择。
更好地理解STS和抑制剂的关键分子途径转移
这些途径改善了高级ST的治疗选择。
Identified the Phosphatase Subunit PPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPP2B AS ASUPPRESSOS STS METASTASIS AND ONE OFNE OFTS
磷蛋白靶标RALA,作为处理高级ST的推定可行的目标。
彻底检验了Rala和密切相关的Ralb的假设是重要且可目标的
STS肿瘤生长和转移的驱动因素至少部分地调节STS计划
控制外泌体生产1:将测试RAL同工型的功能要求
它们在体外和体内的STS生长和转移中的效应子,通过耦合这些体型的遗传沉默
利用特定相互作用的RAL突变体的救援经验。
RAL同工型和STS细胞和外泌体的Prosome生产的基本要求
确定抑制雷尔的外泌体是否控制肿瘤的生长和转移。
STS细胞系和患者衍生的异种移植物,以确定RAL靶向抑制剂的有效性
STS的创新治疗方法。
改善晚期STS治疗的靶标,并确定调节癌症外泌体的新型机制。
该病房弄乱了候选人的受保护时间所需的时间,他从乳腺癌中进行研究 -
专注于STS转移的细小领域,并获得额外的培训,成为一个
癌症相关外泌体领域的领导者。
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 }}
Steven T. Sizemore其他文献
Steven T. Sizemore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('Steven T. Sizemore', 18)}}的其他基金
Determining the role of RALA and RALB in soft tissue sarcoma tumor growth and metastasis
确定 RALA 和 RALB 在软组织肉瘤肿瘤生长和转移中的作用
- 批准号:
9759887 - 财政年份:2017
- 资助金额:
$ 18.68万 - 项目类别:
相似国自然基金
单核细胞产生S100A8/A9放大中性粒细胞炎症反应调控成人Still病发病及病情演变的机制研究
- 批准号:82373465
- 批准年份:2023
- 资助金额:49 万元
- 项目类别:面上项目
成人型弥漫性胶质瘤患者语言功能可塑性研究
- 批准号:82303926
- 批准年份:2023
- 资助金额:30 万元
- 项目类别:青年科学基金项目
MRI融合多组学特征量化高级别成人型弥漫性脑胶质瘤免疫微环境并预测术后复发风险的研究
- 批准号:82302160
- 批准年份:2023
- 资助金额:30 万元
- 项目类别:青年科学基金项目
SERPINF1/SRSF6/B7-H3信号通路在成人B-ALL免疫逃逸中的作用及机制研究
- 批准号:82300208
- 批准年份:2023
- 资助金额:30 万元
- 项目类别:青年科学基金项目
基于动态信息的深度学习辅助设计成人脊柱畸形手术方案的研究
- 批准号:82372499
- 批准年份:2023
- 资助金额:49 万元
- 项目类别:面上项目
相似海外基金
The Role of Glycosyl Ceramides in Heart Failure and Recovery
糖基神经酰胺在心力衰竭和恢复中的作用
- 批准号:
10644874 - 财政年份:2023
- 资助金额:
$ 18.68万 - 项目类别:
3D Methodology for Interpreting Disease-Associated Genomic Variation in RAG2
解释 RAG2 中疾病相关基因组变异的 3D 方法
- 批准号:
10724152 - 财政年份:2023
- 资助金额:
$ 18.68万 - 项目类别:
Development and implementation of a digital sleep intervention for preschoolers in foster care
为寄养中的学龄前儿童开发和实施数字睡眠干预
- 批准号:
10724304 - 财政年份:2023
- 资助金额:
$ 18.68万 - 项目类别:
Implementing Evidence-Based Treatment for Common Mental Disorders in HIV Clinics in Ukraine
在乌克兰艾滋病毒诊所对常见精神疾病实施循证治疗
- 批准号:
10762576 - 财政年份:2023
- 资助金额:
$ 18.68万 - 项目类别: