Applying Innovative Lung Mapping Strategies to Understand Alveolar Capillary Barrier Permeability in ARDS
应用创新的肺标测策略来了解 ARDS 中的肺泡毛细血管屏障渗透性
基本信息
- 批准号:10650403
- 负责人:
- 金额:$ 70.21万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-06-01 至 2027-05-31
- 项目状态:未结题
- 来源:
- 关键词:AcuteAcute Respiratory Distress SyndromeAcute respiratory failureAffectAlveolarAmericanBiological ModelsBlood capillariesCatalogsCellsClinical TrialsCoupledDataDeath RateDevelopmentDiseaseFunctional disorderFutureGene ExpressionGene Expression ProfileGoalsHealthHumanImpairmentIn VitroInstitutionLaboratoriesLifeLungMapsMediatorMethodsMissionModelingMolecularMusNational Heart, Lung, and Blood InstitutePathogenesisPathologicPathologyPatientsPermeabilityPhenotypePre-Clinical ModelProteinsResearchResourcesSepsisStatistical MethodsStructure of parenchyma of lungTestingTissuesTransgenic ModelTransgenic OrganismsTranslatingTranslational ResearchTranslationsclinically relevantcostdesignflexibilityhuman modelin vivoinjuredinnovationinsightlung injurymass spectrometric imagingmortalitymouse modelnew therapeutic targetnovelnovel strategiesnovel therapeuticspre-clinicalpreclinical studyprogramsprotein expressionsingle-cell RNA sequencingsystems researchtargeted treatmenttherapeutic target
项目摘要
Project Summary
This R35 application describes a robust research framework to facilitate discovery and translation of new
therapeutic targets in Acute Respiratory Distress Syndrome (ARDS), a common cause of acute respiratory
failure that carries a high mortality rate and has no beneficial targeted therapies. ARDS remains a significant
health problem affecting 190,000 Americans per year, costing billions of dollars, and leaving the majority of
patients dead or significantly impaired. New insights into the pathogenesis are needed to deepen our
understanding of the underlying mechanisms that lead to ARDS as well as to develop novel therapeutics.
Thus, there is an unmet need to define clinically relevant therapeutic targets that can be studied
mechanistically and rapidly carried through robust pre-clinical studies. For the last 14 years I have been
building my research team to be on the forefront of translational discovery. My group has made major
contributions to understanding ARDS pathophysiology. The major focus of my laboratory is defining the key
cellular and molecular regulators of alveolar capillary barrier function and dysfunction that underlies ARDS
pathology. My R35 research program is designed to identify novel mediators in ARDS using lung tissue
imaging mass spectrometry and deep phenotyping of gene expression profiles at the single cell level coupled
with advanced statistical methods to identify leading targets. New targets will be studied in in vitro transgenic
model systems to define cellular and molecular mechanisms in order to facilitate the development of novel
therapeutics to be tested in pre-clinical models. My research framework is centered on three goals: Discovery,
Mechanism and Translation. Goal 1 – Discovery. To accomplish this goal, we will break new ground using
imaging mass spectrometry and single cell RNA sequencing to create an expression profile and protein “map”
of the injured and uninjured human lung. Using advanced statistical approaches, we will identify promising
targets to take forward into further studies. Goal 2 – Mechanism. Leveraging our existing lung injury models,
institutional resources and new approaches, we will define the fundamental pathologic mechanisms that lead
to alveolar capillary barrier permeability in ARDS by generating novel transgenic cell and mouse lines for
mechanistic studies. Goal 3 – Translation. Building on our existing ex vivo human lung and in vivo mouse
models, we will generate rigorous pre-clinical data based on new targets identified in our Discovery and
Mechanism studies. With this R35, my lab will advance the mission of the NHLBI by: generating a catalogue of
single cell transcription profiles and tissue protein expression levels in acutely injured and uninjured human
lung, identifying novel therapeutic targets in ARDS, defining the cellular and molecular mechanisms regulating
alveolar capillary barrier dysfunction and conducting pre-clinical studies in mouse and human models. The R35
will provide the support and flexibility necessary for me to break new ground in ARDS.
项目总结
项目成果
期刊论文数量(5)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
A preclinical systematic review and meta-analysis assessing the effect of biological sex in lipopolysaccharide-induced acute lung injury.
临床前系统评价和荟萃分析,评估生物性别对脂多糖诱导的急性肺损伤的影响。
- DOI:10.1152/ajplung.00336.2023
- 发表时间:2024
- 期刊:
- 影响因子:0
- 作者:Kuhar,Eva;Chander,Nikesh;Stewart,DuncanJ;Jahandideh,Forough;Zhang,Haibo;Kristof,ArnoldS;Bastarache,JulieA;Schmidt,EricP;Taljaard,Monica;Thébaud,Bernard;Engelberts,Doreen;Fergusson,DeanA;Lalu,ManojM
- 通讯作者:Lalu,ManojM
Association of Vitamin C, Thiamine, and Hydrocortisone Infusion With Long-term Cognitive, Psychological, and Functional Outcomes in Sepsis Survivors: A Secondary Analysis of the Vitamin C, Thiamine, and Steroids in Sepsis Randomized Clinical Trial.
- DOI:10.1001/jamanetworkopen.2023.0380
- 发表时间:2023-02-01
- 期刊:
- 影响因子:13.8
- 作者:
- 通讯作者:
LNK/SH2B3 loss of function increases susceptibility to murine and human atrial fibrillation.
LNK/SH2B3 功能丧失会增加小鼠和人类房颤的易感性。
- DOI:10.1093/cvr/cvae036
- 发表时间:2024
- 期刊:
- 影响因子:10.8
- 作者:Murphy,MatthewB;Yang,Zhenjiang;Subati,Tuerdi;Farber-Eger,Eric;Kim,Kyungsoo;Blackwell,DanielJ;Fleming,MatthewR;Stark,JoshuaM;VanAmburg,JosephC;Woodall,KaylenK;VanBeusecum,JustinP;Agrawal,Vineet;Smart,CharlesD;Pitzer,Ash
- 通讯作者:Pitzer,Ash
Transpulmonary generation of cell-free hemoglobin contributes to vascular dysfunction in pulmonary arterial hypertension via dysregulated clearance mechanisms.
- DOI:10.1002/pul2.12185
- 发表时间:2023-01
- 期刊:
- 影响因子:2.6
- 作者:Meegan, Jamie E.;Kerchberger, Vern Eric;Fortune, Niki L.;McNeil, Joel Brennan;Bastarache, Julie A.;Austin, Eric D.;Ware, Lorraine B.;Hemnes, Anna R.;Brittain, Evan L.
- 通讯作者:Brittain, Evan L.
Cell-Free Hemoglobin Increases Leukocyte Adhesion and Mitochondrial Oxidative Damage in the Pulmonary Microvascular Endothelium.
无细胞血红蛋白增加肺微血管内皮中的白细胞粘附和线粒体氧化损伤。
- DOI:
- 发表时间:2022
- 期刊:
- 影响因子:0
- 作者:Riedmann,KyleJ;Conger,AdrienneK;Meegan,JamieE;Ware,LorraineB;Bastarache,JulieA
- 通讯作者:Bastarache,JulieA
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Julie Anne Bastarache其他文献
Julie Anne Bastarache的其他文献
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{{ truncateString('Julie Anne Bastarache', 18)}}的其他基金
The Sepsis ClinicAl Resource And Biorepository (SCARAB) Project
败血症临床资源和生物储存库 (SCARAB) 项目
- 批准号:
10353314 - 财政年份:2022
- 资助金额:
$ 70.21万 - 项目类别:
Neuroinflammatory mechanisms underlying sepsis-induced cognitive dysfunction
脓毒症引起认知功能障碍的神经炎症机制
- 批准号:
10525755 - 财政年份:2022
- 资助金额:
$ 70.21万 - 项目类别:
Neuroinflammatory mechanisms underlying sepsis-induced cognitive dysfunction
脓毒症引起认知功能障碍的神经炎症机制
- 批准号:
10835675 - 财政年份:2022
- 资助金额:
$ 70.21万 - 项目类别:
The Sepsis ClinicAl Resource And Biorepository (SCARAB) Project
败血症临床资源和生物储存库 (SCARAB) 项目
- 批准号:
10543451 - 财政年份:2022
- 资助金额:
$ 70.21万 - 项目类别:
Applying Innovative Lung Mapping Strategies to Understand Alveolar Capillary Barrier Permeability in ARDS
应用创新的肺标测策略来了解 ARDS 中的肺泡毛细血管屏障渗透性
- 批准号:
10424547 - 财政年份:2020
- 资助金额:
$ 70.21万 - 项目类别:
Applying Innovative Lung Mapping Strategies to Understand Alveolar Capillary Barrier Permeability in ARDS
应用创新的肺标测策略来了解 ARDS 中的肺泡毛细血管屏障渗透性
- 批准号:
9894231 - 财政年份:2020
- 资助金额:
$ 70.21万 - 项目类别:
Potential Protective Mechanisms of Tissue Factor in Acute Lung Injury
组织因子在急性肺损伤中的潜在保护机制
- 批准号:
10045936 - 财政年份:2017
- 资助金额:
$ 70.21万 - 项目类别:
Targeting cell-free hemoglobin in sepsis to reduce lung microvascular permeability: mechanistic and translational studies
靶向脓毒症中的无细胞血红蛋白以降低肺微血管通透性:机制和转化研究
- 批准号:
9922349 - 财政年份:2017
- 资助金额:
$ 70.21万 - 项目类别:
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