SELPLG as a candidate gene in Acute Respiratory Distress Syndrome
SELPLG as a candidate gene in Acute Respiratory Distress Syndrome
批准号:
10383770
负责人:
Christian Bime
金额:
$17.27万
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
项目状态:
已结题
起止时间:
2018-04-09 至 2023-03-31
关键词:
AcuteAcute Respiratory Distress SyndromeAddressAffectAfrican ancestryAntibodiesArizonaBioinformaticsBiologyBlood PlateletsBlood VesselsCandidate Disease GeneCaringClinicalCodeConduct Clinical TrialsCritical CareCritical IllnessDNADNA RepositoryDataDevelopmentE-SelectinEndotheliumExhibitsExtravasationFundingGene ExpressionGene FrequencyGenesGeneticGenetic DeterminismGenotypeIndividualInflammationInflammatoryK-Series Research Career ProgramsL-SelectinLaboratoriesLeadLeukocytesLigandsLuciferasesLungLung infectionsMYLK geneMedicineMentorsMentorshipMinorModelingNot Hispanic or LatinoP-SelectinP-selectin ligand proteinPathway interactionsPatientsPersonsPhenotypePhysiciansPre-Clinical ModelPredispositionPreventiveProteinsRaceRegulationReporterResearchResearch PersonnelRiskRisk FactorsRoleSELE geneSamplingScientistSelectinsSepsisSeveritiesSingle Nucleotide PolymorphismSiteStimulusSusceptibility GeneSystems BiologyTestingTherapeuticTrainingUnited States National Institutes of HealthUniversitiesVariantVentilator-induced lung injuryantagonistattenuationbasebiobankcareercohortdesignexperiencefunctional genomicsgenetic variantgenome wide association studyhealth disparityin vitro activityin vivoindividualized medicineinsightlung injurymortalitymouse modelnon-geneticnovelpersonalized medicinepre-clinicalprofessorprogramspromoterracial disparityrecruitskillstranslational therapeutics
中文摘要
总结/摘要:
本申请为指导临床科学家研究职业发展奖(K 08)解决了
急性呼吸窘迫综合征(ARDS)风险和严重程度的种族差异是一个重要问题,
严重急性危重病,死亡率高(约30%),每年影响多达20万美国患者。
与非非洲裔受试者相比,非洲裔受试者显示出增加的ARDS风险和更高的ARDS死亡率。
西班牙裔白人越来越多的人认识到,遗传因素参与决定
易患ARDS,并可能导致观察到的健康差异。此外,了解
ARDS易感性的遗传决定因素将加速新的个性化预防和
ARDS治疗方法。本K 08申请的PI是医学助理教授,
亚利桑那大学谁渴望职业生涯专注于翻译ARDS研究有关
破译遗传和非遗传因素的基础上观察到的健康差异,在重症监护,
探索成人呼吸窘迫综合征的个性化治疗。PI接受过肺部和重症监护方面的临床培训
医学,以及临床试验设计和实施方面的培训和经验。他现在提议,
将他的研究范围和范围扩展到呼吸窘迫综合症的转化系统生物学项目,
重症监护在Joe GN Garcia医学博士的指导下,他是世界知名的医学科学家,
急性呼吸窘迫综合征,遗传学和健康差异,PI已经产生了重要的初步数据,
一种新的P配体(SELPLG)基因及其编码蛋白,P-选择素糖蛋白配体1(PSGL 1
非洲裔个体的ARDS易感性目标。该研究将采用一个集中的
和全面的系统生物学方法来检验SELPLG和PSGL 1是新的假设
ARDS靶向具有赋予ARDS易感性的遗传变异。具体目标#1(SA #1)将表征
通过ARDS刺激和精心选择的SELPLG启动子SNP对SELPLG表达的调节,
SELPLG基因启动子活性SA#2将表征SELPLG编码SNP对PSGL 1活性的影响,
ARDS的临床前模型。最后,SA #3将评估选择素途径基因SNP与
利用Sequenom MassARRAY基因分型平台在不同井-
表型队列的ARDS患者DNA样品(> 2,000)和健康对照(种族匹配),
储存在我们亚利桑那大学的生物库中。因此,K 08支持的高级培训
基因组学、功能基因组学、生物信息学分析和肺损伤生物学,将有很高的翻译价值。
治疗意义,并将提高PI成功过渡到独立治疗的可能性。
研究生涯主要集中在转化性呼吸窘迫综合症和健康差异上。
英文摘要
SUMMARY/ABSTRACT:
This application for a Mentored Clinical Scientist Research Career Development Award (K08) addresses the
important issue of racial disparities in both risk and severity for acute respiratory distress syndrome (ARDS), a
severe acute critical illness with a high mortality rate (~30%) affecting up to 200,000 US patients each year.
Subjects of African descent exhibit increased ARDS risk and higher ARDS mortality compared with non-
Hispanic whites. It has been increasingly appreciated that genetic factors participate in determining
predisposition to ARDS and may contribute to observed health disparities. Additionally, an understanding of
genetic determinants of ARDS susceptibility will hasten the development of novel personalized preventive and
therapeutic approaches to ARDS care. The PI for this K08 application is an Assistant Professor of Medicine at
the University of Arizona who aspires to a career focused on translational ARDS research related to
deciphering the genetic and non-genetic factors that underlie the observed health disparities in critical care and
to exploring personalized therapies in ARDS. The PI has clinical training in pulmonary and critical care
medicine, as well as training and experience in the design and conduct of clinical trials. He now proposes to
extend the reach and scope of his research towards a translational systems biology program in ARDS and
critical care. Under the mentorship of Joe GN Garcia MD, a world-renowned physician-scientist in the field of
ARDS, genetics, and health disparities, the PI has generated important preliminary data implicating the selectin
P ligand (SELPLG) gene and its encoded protein, P-selectin glycoprotein ligand 1 (PSGL1) as novel
susceptibility targets for ARDS in individuals of African descent. The proposed research will employ a focused
and comprehensive systems biology approach to test the hypothesis that SELPLG and PSGL1 are novel
ARDS targets with genetic variants that confer ARDS susceptibility. Specific Aim #1 (SA #1) will characterize
the regulation of SELPLG expression by ARDS stimuli and carefully-selected SELPLG promoter SNPs on
SELPLG gene promoter activity SA #2 will characterize effects of SELPLG coding SNPs on PSGL1 activity in
preclinical models of ARDS. Finally, SA #3 will assess the association of selectin pathway gene SNPs with
ARDS risk and mortality utilizing the Sequenom MassARRAY genotyping platform on a diverse well-
phenotyped cohort of ARDS patient DNA samples (>2,000) and healthy controls (race-matched) from the DNA
repository stored within our University of Arizona biobank. Thus, the K08-suported training in advanced
genetics, functional genomics, bioinformatic analysis, and lung injury biology, will have high translational
therapeutic implications and will enhance the likelihood that the PI will successfully transition to an independent
research career focused on translational ARDS and health disparities.
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DOI:
10.1002/pul2.12206
发表时间:
2023-01
期刊:
PULMONARY CIRCULATION
影响因子:
2.6
作者:
[Sun, Xiaoguang, Sammani, Saad, Hufford, Matthew, Sun, Belinda L., Kempf, Carrie L., Camp, Sara M., Garcia, Joe G. N., Bime, Christian]
通讯作者:
Bime, Christian
The ARREST Pneumonia Clinical Trial. Rationale and Design.
ARREST 肺炎临床试验。
DOI:
10.1513/annalsats.202009-1115sd
发表时间:
2021
期刊:
Annals of the American Thoracic Society
影响因子:
8.3
作者:
[Levitt,JosephE, Festic,Emir, Desai,Manisha, Hedlin,Haley, Mahaffey,KennethW, Rogers,AngelaJ, Gajic,Ognjen, Matthay,MichaelA, ARRESTPneumoniaClinicalTrialInvestigators]
通讯作者:
ARRESTPneumoniaClinicalTrialInvestigators
High-Flow Oxygen Therapy Concepts: Time to Standardize Nomenclature and Avoid Confusion.
高流量氧疗概念:是时候标准化命名并避免混淆了。
DOI:
10.1177/0885066620908243
发表时间:
2020
期刊:
Journal of intensive care medicine
影响因子:
3.1
作者:
[Miller,DavidC, Bime,Christian, Partharsarathy,Sairam, Mosier,JarrodM]
通讯作者:
Mosier,JarrodM
DOI:
10.1016/j.chest.2021.08.053
发表时间:
2022-01
期刊:
Chest
影响因子:
9.6
作者:
[Bhakta NR, Kaminsky DA, Bime C, Thakur N, Hall GL, McCormack MC, Stanojevic S]
通讯作者:
Stanojevic S
Delayed intubation associated with in-hospital mortality in patients with COVID-19 respiratory failure who fail heated and humified high flow nasal canula.
与院内死亡率相关的延迟插管在19.19呼吸衰竭的患者中失败并衰减了高流量鼻canula。
DOI:
10.1186/s12871-023-02198-7
发表时间:
2023-07-12
期刊:
BMC anesthesiology
影响因子:
2.2
作者:
[]
通讯作者:
共 11 条
Validation of a Genetic-based Biomarker Panel for Stratification of Mortality Risk in ARDS Patients
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批准号:10645784
-
项目类别:
-
资助金额:$11.51万
-
财政年份:2023
-
负责人:Christian Bime
-
依托单位:
Increasing the Success of ARDS Therapeutic Clinical Trials: Novel Trial Design and Targeting of the P-selectin Pathway
-
批准号:10683789
-
项目类别:
-
资助金额:$52.94万
-
财政年份:2022
-
负责人:Christian Bime
-
依托单位:
Targeting polyamines to suppress SARS-CoV-2 related disease
-
批准号:10627308
-
项目类别:
-
资助金额:$15.3万
-
财政年份:2021
-
负责人:Christian Bime
-
依托单位:
SELPLG as a candidate gene in Acute Respiratory Distress Syndrome
-
批准号:9898444
-
项目类别:
-
资助金额:$17.27万
-
财政年份:2018
-
负责人:Christian Bime
-
依托单位:
SELPLG as a candidate gene in Acute Respiratory Distress Syndrome
-
批准号:9505784
-
项目类别:
-
资助金额:$17.27万
-
财政年份:2018
-
负责人:Christian Bime
-
依托单位:
Study of Asthma and Nasal Steroids Trial-An ancillary mechanistic study
-
批准号:8111232
-
项目类别:
-
资助金额:$5.86万
-
财政年份:2010
-
负责人:Christian Bime
-
依托单位:
Study of Asthma and Nasal Steroids Trial-An ancillary mechanistic study
-
批准号:8003100
-
项目类别:
-
资助金额:$5.99万
-
财政年份:2010
-
负责人:Christian Bime
-
依托单位:
海外基金