In vitro synthesis of recombinant heparan sulfate
In vitro synthesis of recombinant heparan sulfate
批准号:
10218239
负责人:
JIAN LIU
金额:
$46.37万
依托单位国家:
美国
项目类别:
财政年份:
2009
资助国家:
美国
项目状态:
已结题
起止时间:
2009-02-13 至 2023-06-30
关键词:
AcetaminophenAcute Liver FailureAdvanced Glycosylation End ProductsAirAnimal ModelAnti-Inflammatory AgentsAntiinflammatory EffectBindingBinding ProteinsBiological AssayBuffaloesCell DeathCell surfaceCellsCessation of lifeCysteineDataDiseaseEnvironmentExtracellular MatrixFundingGoalsHMGB1 ProteinHeart failureHeparitin SulfateHepatocyteHistonesHospitalsHourImmune responseIn VitroInflammationInflammatoryInflammatory ResponseInjuryKnockout MiceLeadLiverLungMethodsMicroarray AnalysisModelingMolecularMusNecrosisNeutrophil InfiltrationNew YorkNorth CarolinaOligosaccharidesOverdosePatientsPatternPharmaceutical PreparationsPlayPolysaccharidesProcessProtective AgentsProteinsRecombinantsReperfusion InjuryResearchRoleS100A8 geneSiteSterilityStructureSulfateTechniquesTestingTherapeuticTherapeutic AgentsTissuesUniversitiesacetaminophen overdoseacute liver injurybasecell injurychemokinecytokinedrug developmenteffectiveness evaluationextracellularliver injuryliver transplantationmigrationmouse modelneutrophilpreventreceptorreceptor for advanced glycation endproductsresponsestandard caresuccesstissue repairtissue-repair responses
中文摘要
摘要
英文摘要
Abstract
This proposal is aimed to develop a method to synthesize structurally defined
heparan sulfated oligosaccharides as therapeutic agents. In the current funding cycle,
we propose to study the role of heparan sulfate in dampening inflammatory responses.
This project is a collaborative effort of three research groups, including Dr. Jian Liu
(University of North Carolina), Dr. Rafal Pawlinski (University of North Carolina), and Dr.
Ding Xu (State University of New York at Buffalo). Acetaminophen overdose causes
hepatocyte cell damage that triggers inflammatory responses for tissue repairing.
However, if this response overreacts, it causes to collateral damages to the liver issues,
leading to acute liver injury. Escalated liver injury leads to the failure of heart and lung,
and ultimately death. We discover a structurally homogeneous heparan sulfate
octadecasaccharide (18-mer) displays strong protection effect for the liver injury induced
by acetaminophen in a murine model. Three specific aims are proposed to understand
the details behind the 18-mer’s protection effect. Aim 1 is to determine the targets for
the effect of 18-mer. Aim 2 is to determine the structural selectivity of heparan sulfate for
the hepatoprotection effect using microarray analysis. Aim 3 is to determine the efficacy
for the delayed treatment for acetaminophen-induced liver injury with a goal to widen the
therapeutic window. Because uncontrolled inflammation is a major contributor to many
diseases, results from our studies will advance anti-inflammatory drug development
focusing heparan sulfate molecules.
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DOI:
10.1016/j.addr.2015.11.002
发表时间:
2016-02-01
期刊:
Advanced drug delivery reviews
影响因子:
16.1
作者:
[Fu L, Suflita M, Linhardt RJ]
通讯作者:
Linhardt RJ
DOI:
10.1160/th11-11-0795
发表时间:
2012-04
期刊:
Thrombosis and haemostasis
影响因子:
6.7
作者:
[Joglekar MV, Quintana Diez PM, Marcus S, Qi R, Espinasse B, Wiesner MR, Pempe E, Liu J, Monroe DM, Arepally GM]
通讯作者:
Arepally GM
DOI:
10.1021/jacs.7b10164
发表时间:
2017-11-22
期刊:
Journal of the American Chemical Society
影响因子:
15
作者:
[Yu Y, Duan J, Leach FE 3rd, Toida T, Higashi K, Zhang H, Zhang F, Amster IJ, Linhardt RJ]
通讯作者:
Linhardt RJ
DOI:
10.1039/c7sc03541a
发表时间:
2017-12-01
期刊:
Chemical science
影响因子:
8.4
作者:
[Zhang X, Pagadala V, Jester HM, Lim AM, Pham TQ, Goulas AMP, Liu J, Linhardt RJ]
通讯作者:
Linhardt RJ
DOI:
10.1039/d0cb00199f
发表时间:
2021-02-22
期刊:
RSC chemical biology
影响因子:
4.1
作者:
[Wang Z, Arnold K, Dhurandhare VM, Xu Y, Liu J]
通讯作者:
Liu J
共 83 条
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批准号:10665752
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资助金额:$53.96万
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财政年份:2022
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资助金额:$14.99万
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财政年份:2017
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PROBING HEPARIN STRUCTURAL ELEMENTS FOR HIGH RISK OF HEPARIN-INDUCED THROMBOCYTOP
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批准号:8730574
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资助金额:$25.0万
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Uncovering the controlling mechanisms in heparan sulfate biosynthesis
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批准号:8853290
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资助金额:$28.47万
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财政年份:2013
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Uncovering the controlling mechanisms in heparan sulfate biosynthesis
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批准号:8576941
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资助金额:$31.07万
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财政年份:2013
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负责人:JIAN LIU
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依托单位:
PROBING HEPARIN STRUCTURAL ELEMENTS FOR HIGH RISK OF HEPARIN-INDUCED THROMBOCYTOP
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批准号:9135956
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项目类别:
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资助金额:$25.0万
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财政年份:2013
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负责人:JIAN LIU
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依托单位:
PROBING HEPARIN STRUCTURAL ELEMENTS FOR HIGH RISK OF HEPARIN-INDUCED THROMBOCYTOP
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批准号:8703471
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项目类别:
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资助金额:$25.0万
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财政年份:2013
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负责人:JIAN LIU
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依托单位:
PROBING HEPARIN STRUCTURAL ELEMENTS FOR HIGH RISK OF HEPARIN-INDUCED THROMBOCYTOP
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批准号:9336703
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项目类别:
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资助金额:$30.0万
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财政年份:2013
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依托单位:
Uncovering the controlling mechanisms in heparan sulfate biosynthesis
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批准号:8724523
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项目类别:
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资助金额:$28.47万
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财政年份:2013
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负责人:JIAN LIU
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依托单位:
PROBING HEPARIN STRUCTURAL ELEMENTS FOR HIGH RISK OF HEPARIN-INDUCED THROMBOCYTOP
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批准号:8892053
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项目类别:
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资助金额:$25.0万
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财政年份:2013
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负责人:JIAN LIU
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依托单位:
Structural Specificity of Heparan Sulfate for Herpes Infections
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批准号:8071314
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项目类别:
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资助金额:$0.75万
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财政年份:2010
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负责人:JIAN LIU
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依托单位:
In vitro synthesis of recombinant heparan sulfate
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批准号:8711536
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资助金额:$37.48万
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财政年份:2009
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依托单位:
In vitro synthesis of recombinant heparan sulfate
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批准号:8578129
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项目类别:
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资助金额:$39.02万
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财政年份:2009
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依托单位:
In vitro synthesis of recombinant heparan sulfate
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批准号:7563439
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资助金额:$37.78万
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财政年份:2009
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依托单位:
In vitro synthesis of recombinant heparan sulfate
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批准号:9069923
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资助金额:$45.6万
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财政年份:2009
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负责人:JIAN LIU
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Glycomics of Heparan Sulfate in Bacterial Pathogenesis
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批准号:7739326
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资助金额:$25.09万
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Glycomics of Heparan Sulfate in Bacterial Pathogenesis
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海外基金