BLR&D Research Career Scientist Award Application
BLR
基本信息
- 批准号:10516022
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-10-01 至 2023-09-30
- 项目状态:已结题
- 来源:
- 关键词:9p21AblationAffectAge YearsAmericanAmerican Cancer SocietyAnimal ModelAppointmentAwardBasic ScienceBiochemistryBiologicalBiological MarkersBladderBladder NeoplasmCDKN2A geneCancer DiagnosticsCancer EtiologyCell LineCell ProliferationCellular biologyCisplatinClinicalClinical ManagementClinical ResearchCollaborationsCommunitiesDataDependenceDevelopmentDiagnosisDiseaseDisease ManagementDoctor of PhilosophyEconomic BurdenEducationEmotionalEnzymesEpigenetic ProcessEuropeanEventExpenditureFacultyFemaleFoundationsFundingGeneral PopulationGenesGeneticGenetically Engineered MouseGoalsGrantGrowthGrowth Factor ReceptorsHealthcareHealthcare SystemsHumanIn VitroIncidenceJournalsKidney CalculiKnock-inKnock-outKnowledgeLaboratoriesLaboratory FindingLaboratory ResearchLesionMalignant NeoplasmsMalignant neoplasm of lungMalignant neoplasm of urinary bladderMedicalMentorsMinorMissionModalityModelingMolecularMorbidity - disease rateMusNamesNatureNew YorkOncogenesPIK3CG genePainPaperPapillaryPapillary NeoplasmPathogenesisPathway interactionsPatient CarePatientsPeer ReviewPersonsPhenotypePhysical SufferingsPlayPostdoctoral FellowPredispositionPrevalencePreventionPrevention strategyPrincipal InvestigatorProceduresProcessPrognosisProgram Research Project GrantsProtein FamilyProteinsPublishingPyruvate KinaseQuality of lifeRNA InterferenceReceptor ActivationReceptor Protein-Tyrosine KinasesRecurrent diseaseResearchResearch ActivityResearch PersonnelResearch SupportResistanceRiskRoleScientistSeriesServicesSignal TransductionSmokerSmokingSpecimenSpinal cord injurySurveysTP53 geneTherapeuticTobacco smoking behaviorTrainingTransgenic OrganismsTranslational ResearchTumor PromotionTumor Suppressor GenesTumor Suppressor ProteinsTumorigenicityUMOD geneUnited States National Academy of SciencesUnited States National Institutes of HealthUniversitiesUrinary tractUrologic DiseasesUrologyVariantVeteransWarburg EffectWomanaging populationanaerobic glycolysisanticancer researchbasebody systemcalcificationcancer cellcancer initiationcancer therapycarcinogenesiscareerchemical carcinogenesisclinical investigationcombinatorialcostdisorder preventiondosageeconomic impactimprovedin vivoinsightinterdisciplinary collaborationinterestinventionlifetime risklost work timemalemembermenmolecular subtypesmortalitymouse modelmultidisciplinarymuscle invasive bladder cancerneglectnon-smokernovelnovel diagnosticsnovel strategiesoverexpressionpain reliefsmall moleculesmoking-related cancersocioeconomicstargeted treatmenttooltreatment strategytumortumor initiationtumor progressionurinaryurologic
项目摘要
This renewal application for Research Career Scientist (RCS) award seeks to continue the ongoing research
activities by the incumbent that have been focused on the molecular pathogenesis of major urinary tract
diseases including bladder cancer and kidney stone. Both diseases are highly prevalent among the Veterans,
and inflict considerable emotional and physical suffering and staggering medical expenses. Despite the
socioeconomic impact, research into the molecular pathogenesis of these diseases remains extremely limited,
thus hampering the development of new diagnostic, therapeutic and preventive strategies. During the last
award period, the laboratory of the RCS has made significant inroads in defining the key genetic and
epigenetic determinants underlying the initiation and progression of bladder cancer and kidney stone. With
respect to bladder cancer, the laboratory of the RCS identified several specific combinatorial genetic drivers
that are responsible for the genesis and progression of the two major phenotypic variants of bladder cancer,
e.g., low-grade superficial papillary tumors versus high-grade invasive tumors. Using a broad range of
technical approaches including cultured cell lines, genetically engineered mice, chemical carcinogenesis,
analysis of human specimens and high-throughput profiling, the laboratory found that the activation of receptor
tyrosine kinase (RTK)/RAS/PI3K pathway collaborates with the loss of 9p21 tumor suppressors (e.g., CDKN2A
and CDKN2B) to induce low-grade superficial papillary bladder cancer, and that the same activated
RTK/RAS/PI3K pathway collaborates with the deficiency of RB family proteins or that of the p53 pathway
effectors to induce high-grade muscle-invasive bladder cancer. In another series of studies supported by a VA
Merit Review award, the laboratory of the RCS demonstrated that pyruvate kinase 2 (PKM2), a key enzyme in
anaerobic glycolysis or Warburg effect, is upregulated in most bladder cancers and plays a critical role in
bladder cancer cell proliferation, and that genetic ablation of PKM2 markedly reduces bladder cancer growth in
vitro and in vivo. Inhibition of PKM2 by RNAi or small molecules also greatly decreases the acquired resistance
of bladder cancer cells to cisplatin. These and other data to be detailed in the proposal are highly significant in
not only improving our understanding of the molecular bases of bladder cancer pathogenesis, but also offer
practical insights into novel strategies for bladder cancer diagnostics and treatment. With respect to kidney
stone, the laboratory of the RCS continued to make major progress in unraveling the role and mechanisms of
action of Tamm-Horsfall protein (THP or uromodulin), the most abundant urinary protein in humans, in urinary
tract defense against kidney stone formation. The deficiency of THP renders animal models more susceptible
to intra-renal calcification, via increased urinary supersaturation, that strongly resembles the early stages of
idiopathic stone formation in humans. Because THP deficiency is often observed in patients, such data will
have major implications on kidney stone pathogenesis and prevention. In the past four and a half years, the
RCS obtained a VA Merit Award, a multidisciplinary NIH Program Project (PO1) grant and an NIH RO1 grant;
published 49 peer-reviewed papers; spearheaded multiple collaborative projects with VA and non-VA
investigators; continued to actively train junior faculty members and postdoctoral fellows; provided important
services to local and national VA, university affiliates and research community at large. These
accomplishments set the stage for the RCS to continue and expand his contributions to the mission of VA and
university affiliates in helping advance research, education, patient care, mentoring, services and
interdisciplinary collaborations.
这项研究职业科学家(RCS)奖的更新申请旨在继续进行正在进行的研究
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 }}
XUE-RU WU其他文献
XUE-RU WU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('XUE-RU WU', 18)}}的其他基金
BCCMA: Basic and Translational Mechanisms of Cancer Initiation of the Urothelium in Veterans Exposed to Carcinogens: Role of PPARg in theFormation and Progression of Carcinoma in situ of the Bladder
BCCMA:暴露于致癌物的退伍军人尿路上皮癌症发生的基本和转化机制:PPARg 在膀胱原位癌形成和进展中的作用
- 批准号:
10361590 - 财政年份:2022
- 资助金额:
-- - 项目类别:
BCCMA: Basic and Translational Mechanisms of Cancer Initiation of the Urothelium in Veterans Exposed to Carcinogens: Role of PPARg in theFormation and Progression of Carcinoma in situ of the Bladder
BCCMA:暴露于致癌物的退伍军人尿路上皮癌症发生的基本和转化机制:PPARg 在膀胱原位癌形成和进展中的作用
- 批准号:
10616472 - 财政年份:2022
- 资助金额:
-- - 项目类别:
Role of Tamm-Horsfall Protein in Urinary Tract Defense
Tamm-Horsfall 蛋白在尿路防御中的作用
- 批准号:
8785878 - 财政年份:2014
- 资助金额:
-- - 项目类别:
Molecular and Genetic Studies of Bladder Tumorigenesis
膀胱肿瘤发生的分子和遗传学研究
- 批准号:
10427138 - 财政年份:2013
- 资助金额:
-- - 项目类别:
相似海外基金
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:
-- - 项目类别:
Grant-in-Aid for Early-Career Scientists
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:
-- - 项目类别:
Grant-in-Aid for Scientific Research (C)
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:
-- - 项目类别:
Grant-in-Aid for Scientific Research (C)
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:
-- - 项目类别:
Fellowship
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:
-- - 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:
-- - 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:
-- - 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:
2334776 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Continuing Grant
Cryo laser-ablation system (157+193nm) with 'triple-quad' plasma mass spectrometer, Cryo-LA-ICPMS/MS
带有“三重四极杆”等离子体质谱仪、Cryo-LA-ICPMS/MS 的冷冻激光烧蚀系统 (157 193nm)
- 批准号:
515081333 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Major Research Instrumentation
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:
-- - 项目类别:
Standard Grant














{{item.name}}会员




