Supplement for MIRA award_Wong_2021
Supplement for MIRA award_Wong_2021
批准号:
10389655
负责人:
HECTOR R. WONG
金额:
$7.7万
依托单位国家:
美国
项目类别:
财政年份:
2018
资助国家:
美国
项目状态:
已结题
起止时间:
2018-04-01 至 2023-03-31
关键词:
AdolescentAdultAgeAwardBackBasic ScienceBiologicalBiological databasesChildChildhoodClinicalClinical DataClinical ResearchCollaborationsCritical CareDataDatabasesDevelopmentDiagnosisDiagnosticFailureFoundationsHeterogeneityImmune responseInvestigationLaboratoriesMeasuresMedicineMulticenter StudiesNational Institute of General Medical SciencesOutcomePathway interactionsPatient CarePhenotypePublic HealthResearchResearch PersonnelRiskSamplingSepsisTestingTrainingTraining ProgramsTranslational ResearchTranslationsbasebench to bedsidecatalystclinical databaseclinically relevantdata repositorygenome-widemouse modelnew therapeutic targetnovel therapeuticsoutcome predictionpathogenprognosticprogramsrepositoryresponsestemtranscriptomicstranslational studyvalidation studies
中文摘要
摘要(原始申请)
脓毒症仍然是成人和儿童的主要全球公共卫生问题。异质性
多水平是临床脓毒症的一个重要方面。直接在该领域存在许多重大空白
源于这种异质性。有必要更好地了解宿主对
脓毒症,宿主衰竭的途径,并确定新的治疗靶点。有必要了解
发育年龄如何影响宿主对败血症的反应需要更可靠地诊断
败血症,包括早期病原体分类鉴定。需要有效地预测结果,
评估不良结局的风险如何随着当前和新疗法的变化而变化。有一个
需要表征脓毒症的生物学和表型亚类(内型),以及这些内型如何
对治疗有不同的反应简而言之,需要更好地解释
脓毒症时照顾病人和进行研究。因此,本报告的业务主题
建议通过基础和转化研究来测量和理解脓毒症异质性
从床边到长凳再到床边自2004年以来,我们领导了一项多中心研究,
维护和发展一个强大的生物样本库,并结合全面的临床数据,
败血症的孩子使用全基因组,以发现为导向,转录组学研究为基础,我们
已经利用这个数据库的各种发现,具有直接转化为临床的潜力。我们
我还利用这些数据,与一些研究人员合作,将我们的研究扩展到患有败血症的成年人。
成人重症监护医学的研究人员。该实验室积极从事基础研究
包括成人和小儿败血症小鼠模型,从而为我们的临床研究提供了一个强大的测试基础。
发现和观察。事实上,我们所有目前和计划中的实验室研究工作都是
由我们的败血症儿童临床和生物学数据库中的发现驱动。的
实验室还支持NIGMS赞助的T32培训计划,该计划目前已存在24年,
PI担任联合项目总监。我们提出了一个研究计划,
全方位的翻译,从床边到长凳再到床边。我们的临床和生物学数据库将
用于产生关于脓毒症病理生物学的假设,这些假设将在鼠模型中进行测试,
随后被带回床边,以推进诊断,预后和治疗方法,
败血症这一框架为合作和培训提供了坚实的基础,并将继续成为一个
新调查的催化剂和新的调查人员一样。
英文摘要
ABSTRACT (original application)
Sepsis continues to be a major, worldwide public health problem in both adults and children. Heterogeneity at
multiple levels is an important aspect of clinical sepsis. There are many major gaps in the field directly
stemming from this heterogeneity. There is a need to better understand the fundamental host responses to
sepsis, the pathways to host failure, and to identify novel therapeutic targets. There is a need to understand
how developmental age influences the host response to sepsis. There is a need to more reliably diagnose
sepsis, including earlier pathogen class identification. There is a need to effectively predict outcomes and
assess how the risks for bad outcomes change in response to both current and novel therapies. There is a
need to characterize biological and phenotypic subclasses (endotypes) of sepsis, and how those endotypes
differentially respond to therapies. In short, there is a need to better account for the intrinsic heterogeneity of
sepsis when caring for patients and when conducting research. Accordingly, the operational themes of this
proposal are measuring and understanding sepsis heterogeneity through basic and translational research
using a bedside to bench to bedside approach. Since 2004, we have led a multi-center study to create,
maintain, and grow a robust repository of biological samples combined with comprehensive clinical data for
children with sepsis. Using genome-wide, discovery-oriented, transcriptomic studies as the foundation, we
have leveraged this database for various discoveries having direct translational potential to the bedside. We
have also leveraged these data to expand our studies to adults with sepsis in collaboration with a number of
investigators based in adult critical care medicine. The laboratory is actively engaged in basic research
involving adult and pediatric murine models of sepsis, thus providing a robust testing ground for our clinical
discoveries and observations. In fact, all of our current and planned laboratory-based research efforts are
driven by discoveries generated from our clinical and biological database of children with sepsis. The
laboratory also supports a NIGMS-sponsored T32 training program that is currently in its 24th year of existence,
and for which the PI serves as the Co-Program Director. We propose a program of research that encompasses
the full range of translation, from bedside to bench to bedside. Our clinical and biological data repository will be
leveraged to generate hypotheses about the pathobiology of sepsis that will be tested in murine models and
subsequently brought back to the bedside to advance diagnostic, prognostic, and treatment approaches in
sepsis. This framework provides a strong foundation for collaboration and training and will continue to be a
catalyst for new investigations and new investigators alike.
期刊论文(20)
专著(0)
科研奖励(0)
会议论文
DOI:
10.1186/s13054-023-04535-1
发表时间:
2023-06-26
期刊:
Critical care (London, England)
影响因子:
--
作者:
[Atreya MR, Cvijanovich NZ, Fitzgerald JC, Weiss SL, Bigham MT, Jain PN, Schwarz AJ, Lutfi R, Nowak J, Allen GL, Thomas NJ, Grunwell JR, Baines T, Quasney M, Haileselassie B, Alder MN, Lahni P, Ripberger S, Ekunwe A, Campbell KR, Walley KR, Standage SW]
通讯作者:
Standage SW
Sepsis from Bedside to Bench to Bedside
-
批准号:9898384
-
项目类别:
-
资助金额:$50.59万
-
财政年份:2018
-
负责人:HECTOR R. WONG
-
依托单位:
PCSK9 and Pediatric Sepsis-Related MODS
-
批准号:9756433
-
项目类别:
-
资助金额:$19.88万
-
财政年份:2018
-
负责人:HECTOR R. WONG
-
依托单位:
Sepsis from Bedside to Bench to Bedside
-
批准号:10132344
-
项目类别:
-
资助金额:$50.57万
-
财政年份:2018
-
负责人:HECTOR R. WONG
-
依托单位:
Novel diagnostic and stratification tools for septic shock
-
批准号:8841381
-
项目类别:
-
资助金额:$48.95万
-
财政年份:2014
-
负责人:HECTOR R. WONG
-
依托单位:
Novel diagnostic and stratification tools for septic shock
-
批准号:9234036
-
项目类别:
-
资助金额:$48.95万
-
财政年份:2014
-
负责人:HECTOR R. WONG
-
依托单位:
Novel diagnostic and stratification tools for septic shock
-
批准号:8695557
-
项目类别:
-
资助金额:$50.36万
-
财政年份:2014
-
负责人:HECTOR R. WONG
-
依托单位:
Novel diagnostic and stratification tools for septic shock
-
批准号:8970115
-
项目类别:
-
资助金额:$30.07万
-
财政年份:2014
-
负责人:HECTOR R. WONG
-
依托单位:
Stratification of pediatric septic shock
-
批准号:8366660
-
项目类别:
-
资助金额:$37.31万
-
财政年份:2012
-
负责人:HECTOR R. WONG
-
依托单位:
Stratification of pediatric septic shock
-
批准号:8525406
-
项目类别:
-
资助金额:$33.58万
-
财政年份:2012
-
负责人:HECTOR R. WONG
-
依托单位:
Stratification of pediatric septic shock
-
批准号:8697067
-
项目类别:
-
资助金额:$37.31万
-
财政年份:2012
-
负责人:HECTOR R. WONG
-
依托单位:
MMP-8 as a novel therapeutic target in sepsis
-
批准号:8245762
-
项目类别:
-
资助金额:$29.07万
-
财政年份:2011
-
负责人:HECTOR R. WONG
-
依托单位:
MMP-8 as a novel therapeutic target in sepsis
-
批准号:8077606
-
项目类别:
-
资助金额:$29.05万
-
财政年份:2011
-
负责人:HECTOR R. WONG
-
依托单位:
MMP-8 as a novel therapeutic target in sepsis
-
批准号:8634800
-
项目类别:
-
资助金额:$29.07万
-
财政年份:2011
-
负责人:HECTOR R. WONG
-
依托单位:
MMP-8 as a novel therapeutic target in sepsis
-
批准号:8449299
-
项目类别:
-
资助金额:$28.05万
-
财政年份:2011
-
负责人:HECTOR R. WONG
-
依托单位:
Genomic analysis of pediatric SIRS and septic shock
-
批准号:7827547
-
项目类别:
-
资助金额:$27.5万
-
财政年份:2009
-
负责人:HECTOR R. WONG
-
依托单位:
THE PEDIATRIC SEPSIS BIOMARKER RISK MODEL
-
批准号:7829817
-
项目类别:
-
资助金额:$50.0万
-
财政年份:2009
-
负责人:HECTOR R. WONG
-
依托单位:
THE PEDIATRIC SEPSIS BIOMARKER RISK MODEL
-
批准号:7933807
-
项目类别:
-
资助金额:$49.96万
-
财政年份:2009
-
负责人:HECTOR R. WONG
-
依托单位:
Genomic Analysis of Pediatric SIRS
-
批准号:6780998
-
项目类别:
-
资助金额:$53.83万
-
财政年份:2003
-
负责人:HECTOR R. WONG
-
依托单位:
Genomic analysis of pediatric SIRS and septic shock
-
批准号:7488514
-
项目类别:
-
资助金额:$32.86万
-
财政年份:2003
-
负责人:HECTOR R. WONG
-
依托单位:
Genomic Analysis of Pediatric SIRS
-
批准号:6678250
-
项目类别:
-
资助金额:$60.71万
-
财政年份:2003
-
负责人:HECTOR R. WONG
-
依托单位:
海外基金