Supplement for MIRA award_Wong_2021

MIRA 奖补充材料_Wong_2021

基本信息

批准号：
10389655
负责人：
HECTOR R. WONG
金额：
$ 7.7万
依托单位：
CINCINNATI CHILDRENS HOSP MED CTR
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：
2018-04-01 至 2023-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10389655
关键词：
Adolescent Adult Age Award Back Basic Science Biological Biological databases Child Childhood Clinical Clinical Data Clinical Research Collaborations Critical Care Data Databases Development Diagnosis Diagnostic Failure Foundations Heterogeneity Immune response Investigation Laboratories Measures Medicine Multicenter Studies National Institute of General Medical Sciences Outcome Pathway interactions Patient Care Phenotype Public Health Research Research Personnel Risk Sampling Sepsis Testing Training Training Programs Translational Research Translations base bench to bedside catalyst clinical database clinically relevant data repository genome-wide mouse model new therapeutic target novel therapeutics outcome prediction pathogen prognostic programs repository response stem transcriptomics translational study validation studies

项目摘要

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.

摘要（原始申请）脓毒症仍然是成人和儿童的一个主要的全球公共卫生问题。异质性多层次是临床脓毒症的一个重要方面。直接领域存在很多重大差距源于这种异质性。有必要更好地了解宿主的基本反应脓毒症、宿主衰竭的途径以及确定新的治疗靶点。有必要了解一下发育年龄如何影响宿主对脓毒症的反应。需要更可靠的诊断脓毒症，包括早期病原体类别鉴定。需要有效地预测结果并评估不良结果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的反应不同。简而言之，需要更好地解释事物的内在异质性。护理患者和进行研究时败血症。据此，本次活动的经营主题提案是通过基础和转化研究来衡量和理解脓毒症异质性采用床边到长凳到床边的方法。自 2004 年以来，我们领导了一项多中心研究，旨在创建、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患有败血症的儿童。以全基因组、以发现为导向的转录组研究为基础，我们利用该数据库获得了具有直接转化潜力到临床的各种发现。我们还与许多人合作，利用这些数据将我们的研究扩展到患有脓毒症的成人成人重症监护医学研究人员。实验室积极从事基础研究涉及脓毒症的成人和儿童小鼠模型，从而为我们的临床提供了强大的测试基础发现和观察。事实上，我们当前和计划的所有基于实验室的研究工作都是由我们的脓毒症儿童临床和生物学数据库中的发现驱动。这实验室还支持 NIGMS 赞助的 T32 培训计划，该计划目前已开展了 24 年， PI 担任联合项目总监。我们提出了一项研究计划，其中包括全方位的翻译，从床边到工作台再到床边。我们的临床和生物数据存储库将是用于产生有关脓毒症病理学的假设，该假设将在小鼠模型中进行测试随后回到临床，以推进诊断、预后和治疗方法败血症。该框架为协作和培训奠定了坚实的基础，并将继续成为新调查和新调查人员的催化剂。

项目成果

期刊论文数量（20）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Prospective clinical testing and experimental validation of the Pediatric Sepsis Biomarker Risk Model.

儿科败血症生物标志物风险模型的前瞻性临床测试和实验验证。

DOI：
发表时间：
2019
期刊：
影响因子：
17.1
作者：
Wong, Hector R;Caldwell, J Timothy;Cvijanovich, Natalie Z;Weiss, Scott L;Fitzgerald, Julie C;Bigham, Michael T;Jain, Parag N;Schwarz, Adam;Lutfi, Riad;Nowak, Jeffrey;Allen, Geoffrey L;Thomas, Neal J;Grunwell, Jocelyn R;Baines, Torrey;Quasney
通讯作者：
Quasney

Biomarkers for Estimating Risk of Hospital Mortality and Long-Term Quality-of-Life Morbidity After Surviving Pediatric Septic Shock: A Secondary Analysis of the Life After Pediatric Sepsis Evaluation Investigation.

用于估计小儿败血性休克幸存后医院死亡率和长期生活质量发病率风险的生物标志物：小儿败血症评估调查后生活的二次分析。

DOI：
发表时间：
2021-01-01
期刊：
影响因子：
0
作者：
Wong, Hector R;Reeder, Ron W;Banks, Russell;Berg, Robert A;Meert, Kathleen L;Hall, Mark W;McQuillen, Patrick S;Mourani, Peter M;Chima, Ranjit S;Sorenson, Samuel;Varni, James W;McGalliard, Julie;Zimmerman, Jerry J;
通讯作者：

Olfactomedin 4 marks a subset of neutrophils in mice.

Olfactomedin 4 标记小鼠中性粒细胞的一个子集。