BLR&D Research Career Scientist Award Application
BLR
基本信息
- 批准号:10618275
- 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:2019
- 资助国家:美国
- 起止时间:2019-04-01 至 2024-03-31
- 项目状态:已结题
- 来源:
- 关键词:Acute DiseaseAddressAdjuvantAdultAerosolsAfghanistanAgingAmerican Association for the Advancement of ScienceAmerican Cancer SocietyAntigen PresentationAntigen Presentation PathwayAntigensAppointmentAreaAwardBasic ScienceBiochemicalBiochemical ProcessBiochemistryBiologicalBiologyBotanyCD8-Positive T-LymphocytesCell physiologyCellsCellular biologyCessation of lifeChemistryChronicChronic DiseaseClinicalClinical ManagementCollaborationsCommunicable DiseasesCountryCytotoxic T-LymphocytesDental SchoolsDiagnosisDiseaseDoctor of PhilosophyDrug resistanceDrug resistant Mycobacteria TuberculosisEffector CellEpitopesExposure toFoundationsFunctional disorderFunding AgencyGenerationsGenomic approachGoalsGrantHealthImmuneImmune responseImmune systemImmunityImmunologic MemoryImmunologic SurveillanceImmunologicsImmunologyIncidenceIndiaInfectionInfectious AgentInstitutionInternationalInvestmentsIraqJapanJournalsKoreaLaboratoriesLipidsLungMaintenanceMalignant NeoplasmsMediatingMedicineMemoryMentorsMicrobiologyMilitary PersonnelModelingMolecularMorbidity - disease rateMucosal ImmunityMucous MembraneMulti-Drug ResistanceMycobacterium tuberculosisOutcomePathologyPeer ReviewPennsylvaniaPeptidesPharmaceutical PreparationsPhysiologyPlayPoxviridaePre-Clinical ModelPredispositionPrivatizationProcessProteinsProteomicsPublicationsPublishingRegimenReportingResearchResearch PersonnelResearch SupportRespiratory Tract InfectionsRoleScienceScientistSiteSubunit VaccinesSurfaceSystemT-LymphocyteT-Lymphocyte EpitopesTestingTissuesTuberculosisTuberculosis diagnosisUnited States National Institutes of HealthUniversitiesVaccinatedVaccinationVaccine DesignVaccinesVeteransVirginiaVisitWarWorkZoologyaustincareerclinical practicecollegedesignfaculty researchgraduate schoolhumanized mouseimmunoreactionindexinginsightinterdisciplinary approachmicrobialmicroorganism antigenmilitary veteranmortalitymouse modelnanoparticlepathogenpathogenic microbepre-clinicalpreventprofessorprogramsresistant strainrespiratorysealtenure tracktissue resident memory T celltranslational medicinetransmission processvaccine candidatevaccine deliveryvaccine development
项目摘要
The overarching goal of my research program is to understand the molecular mechanisms of immune
surveillance mediated by tissue-resident memory T cells that patrol the mucosal barrier of the lungs to control
infectious diseases and cancers. My laboratory is best recognized for its contributions to the cell biology and
biochemistry of MHC and MHC-like CD1d molecules. These molecules play important roles in protein and
lipid antigen presentation and, thereby, control T cell and natural killer T (NKT) cell biology, respectively. In
recent years, our research focus has turned toward harnessing what we have learnt in basic immunology to
augment immune reaction through vaccine and adjuvant design to prevent or treat microbial infections and
cancer, deathly diseases that ail humankind: We recently reported a strategy for CD8+ T cell-targeted vaccine
design to identify targets that confer protective immunity against poxvirus disease (J. Clin. Invest. 123: 1976—
1987;; 2013). Using this model, we have elucidated the mechanisms of induction, maintenance and action of
tissue resident memory (Trm) CD8+ T cells and how Trm cells impart lung/pulmonary mucosal immunity (Cell
Rep 16: 1800;; 2016). New work supported by the Research Career Scientist and the VA Merit will refine the
above strategies to devise ways to identify, characterize and develop vaccine candidates against tuberculosis.
Aims of this project are, (a) to identify T cell epitopes that will protect against pulmonary M tuberculosis
infection in a preclinical humanized mouse model;; (b) to identify globally protective epitopes that cross MHC
restriction barriers;; and (c) to characterize nanoparticle-based delivery systems for intracellular STING-
targeted adjuvant and antigen delivery. Hence, as a Research Career Scientist, I hope to identify T cell
epitopes that will protect against tuberculosis and devise ways to enhance immunological memory at the lung
mucosal surfaces by vaccinating with subunit vaccines and intracellular adjuvants. This outcome will impact
clinical management of tuberculosis as well as other respiratory infectious diseases and cancers.
My research program was developed through numerous collaborations with investigators at the VA, the
University Affiliate, the NIH, and at national and international institutions. I have published over 120 articles,
several in top-tier journals. These works have been cited over 9,700 times, and have an h-index of 48 and an
i10-index of 93. Significantly, our research has been continuously supported by federal grants over the last
20+ years and by a VA Merit Award over the last four years. In sum, I am well-poised to serve our Veterans
as a Research Career Scientist. Through this appointment, I hope to enhance research in vaccines and
vaccine delivery mechanisms that will utilize T cell epitopes. The emerging vaccines and delivery mechanisms
will enhance immunological memory at the lung mucosal surfaces through vaccination with subunit vaccines
and intracellular adjuvants to mediate protective immunity against infectious diseases and cancers.
Our Veterans are exposed to deathly infectious diseases, such as tuberculosis and cancers. For example,
the wars in Afghanistan and Iraq as well as deployment in Korea and other South Eastern countries have
contributed to the tuberculosis incidence in the US Military. A recent study identified 113 Veterans in Western
US with confirmed tuberculosis diagnosis between 2010—2013. The incidence has since risen amongst our
Veterans. Another study noted that of the 42 Veterans diagnosed with latent TB, only ~43% had initiated
treatment and only ~31% had completed the drug regimen. This foretells a grim situation as the untreated
Veteran population, especially those with latent TB infection, are potential disease transmitters;; still worse,
those that do not complete the drug regimen can raise drug-resistant strains for transmission. Hence, our
research and its outcomes will directly impact clinical practice paradigms against tuberculosis and other
respiratory infectious diseases. Thus, our research will better the lives of Veterans.
我的研究计划的首要目标是了解免疫的分子机制,
由组织中驻留的记忆T细胞介导的监视,T细胞巡逻肺粘膜屏障,
传染病和癌症。我的实验室是最好的承认其贡献的细胞生物学,
这些分子在蛋白质和免疫反应中起着重要的作用,
脂质抗原呈递,从而分别控制T细胞和自然杀伤T(NKT)细胞生物学。
近年来,我们的研究重点已经转向利用我们在基础免疫学中所学到的知识,
通过疫苗和佐剂设计增强免疫反应,以预防或治疗微生物感染,
癌症,折磨人类的致命疾病:我们最近报道了一种CD 8 + T细胞靶向疫苗的策略
设计以鉴定赋予针对痘病毒病的保护性免疫的靶标(J.Clin.Invest.123:1976-
1987; 2013年)。使用这个模型,我们已经阐明了诱导,维持和行动的机制,
组织驻留记忆(Trm)CD 8 + T细胞以及Trm细胞如何赋予肺/肺粘膜免疫(细胞免疫)
Rep 16:1800; 2016年6月)。由研究职业科学家和VA Merit支持的新工作将完善
在上述战略中,我们提出了确定、鉴定和开发结核病候选疫苗的方法。
该项目的目的是:(a)鉴定能够预防肺结核分枝杆菌的T细胞表位
临床前人源化小鼠模型中的感染;鉴定(B)跨MHC的全局保护性表位
限制性屏障;(c)表征用于细胞内STING的基于纳米颗粒的递送系统
因此,作为一名研究职业科学家,我希望能够识别T细胞,
这些表位可以预防结核病,并设计出增强肺部免疫记忆的方法。
通过接种亚单位疫苗和细胞内佐剂,对粘膜表面进行免疫。
结核病以及其他呼吸道传染病和癌症的临床管理。
我的研究项目是通过与VA的研究人员进行多次合作开发的,
大学附属机构,国家卫生研究院,并在国家和国际机构。我已经发表了120多篇文章,
这些作品被引用超过9,700次,h-10指数为48,
值得注意的是,我们的研究在过去几年中一直得到联邦赠款的支持。
20多年来,我在过去的四年里获得了退伍军人管理局的优秀奖。总之,我准备好为我们的退伍军人服务
作为一名研究职业科学家。通过这次任命,我希望加强疫苗研究,
新出现的疫苗和递送机制
将通过接种亚单位疫苗增强肺粘膜表面的免疫记忆
和细胞内佐剂以介导针对感染性疾病和癌症的保护性免疫。
我们的退伍军人暴露于致命的传染病,如肺结核和癌症。例如,
阿富汗和伊拉克战争以及在韩国和其他东南部国家的部署,
最近的一项研究确定了113名退伍军人在西部
2010-2013年间确诊结核病的美国患者。此后,
另一项研究指出,在42名被诊断为潜伏性结核病的退伍军人中,只有约43%的人开始了
治疗,只有约31%的人完成了药物治疗。这预示着一个严峻的形势,
退伍军人,特别是那些潜伏结核病感染者,是潜在的疾病传播者;更糟糕的是,
那些没有完成药物治疗方案的人可能会产生耐药菌株进行传播。因此,
研究及其结果将直接影响结核病和其他疾病的临床实践模式,
呼吸道传染病。因此,我们的研究将改善退伍军人的生活。
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)
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{{ truncateString('SEBASTIAN JOYCE', 18)}}的其他基金
Vaccinating at Mucosal Surfaces with Nanoparticle-conjugated Antigen and Adjuvant
使用纳米颗粒结合的抗原和佐剂在粘膜表面进行疫苗接种
- 批准号:
10587388 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Molecular Basis of CD1D and Natural Killer T Cell Function
CD1D 和自然杀伤 T 细胞功能的分子基础
- 批准号:
10203802 - 财政年份:2019
- 资助金额:
-- - 项目类别:
Molecular Basis of CD1D and Natural Killer T Cell Function
CD1D 和自然杀伤 T 细胞功能的分子基础
- 批准号:
10443746 - 财政年份:2019
- 资助金额:
-- - 项目类别:
Head & Neck Cancer Neoantigen Characterization & Therapeutic Targeting
头
- 批准号:
10436179 - 财政年份:2018
- 资助金额:
-- - 项目类别:
Head & Neck Cancer Neoantigen Characterization & Therapeutic Targeting
头
- 批准号:
10180937 - 财政年份:2018
- 资助金额:
-- - 项目类别:
Vaccinating at Mucosal Surfaces with Nanoparticle Conjugated Antigen and Adjuvant
用纳米颗粒缀合抗原和佐剂在粘膜表面进行疫苗接种
- 批准号:
8974276 - 财政年份:2014
- 资助金额:
-- - 项目类别:
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