KLF2 Mediated HIF-1 Regulation and Macrophage Activation
KLF2 Mediated HIF-1 Regulation and Macrophage Activation
批准号:
8327773
负责人:
Ganapati Holanagadde Mahabaleshwar
金额:
$24.9万
依托单位国家:
美国
项目类别:
财政年份:
2011
资助国家:
美国
项目状态:
已结题
起止时间:
2011-09-06 至 2014-06-30
关键词:
AffectAtherosclerosisAwardDevelopmentDiseaseFoundationsFundingGene ExpressionGoalsHypoxiaHypoxia Inducible FactorInflammationInflammatory ResponseInstructionMacrophage ActivationMatrix MetalloproteinasesMediatingMolecularMolecular GeneticsPathogenesisPathologicPhasePhysiologicalPlayProductionRegulationResearch PersonnelResolutionRoleSepsisTissuesTrainingTranslatingUnited States National Institutes of Healthbasecytokinein vivoinhibitor/antagonistloss of functionmacrophagenovelnovel strategiesresponsetumor
中文摘要
炎症反应在调节广泛的生理和病理状态方面是至关重要的。
英文摘要
The inflammatory response is critical in regulating a broad spectrum of physiologic and pathologic states.
The tissue macrophage is a central regulator of this response - from initiation to resolution o inflammation.
Recent studies have identified Hypoxia-inducible Factor 1alpha(HlF-1 alpha) as a key regulator of
macrophage activation function. Using a combination of gain- and loss-of-function approaches, the PI has
identified KLF2 as a novel endogenous regulator of HlF-1 alpha expression and function. Specifically, our
studies show that (1) KLF2 inhibits HlF-1 expression and transcriptional activity; (2) altering KLF2
expression affects HIF-lalpha target gene expression, ATP production, cytokine/MMP expression, and
bacterial/tumoricidal activity of macrophages. In this proposal a cornbination of molecular and genetic
approaches will be undertaken (1) to determine the molecular basis for KLF2-mediated inhibition of
HIF-lalpha expression, (2) to evaluate the effect of altering KLF2 levels on hypoxia or LPS mediated
activation of macrophages, and (3) to assess the effect of altering KLF2 levels on hypoxia or LPS-mediated
macrophage function in vivo. These studies will provide the foundation for the applicant to achieve his longterm
goals of translating basic mechanisms of inflammation toward the development of novel therapies.
Continuing support of this project via a ROO award would play a pivotal and requisite role in the Pi's
development into an independent investigator. The Pl has completed requisite additional training during the
K99 phase of award and is now transiting toward becoming an NIH-funded independent investigator with
adequate institutional support.
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会议论文
Role of KLF6 in macrophage lipid homeostasis and atherogenesis
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批准号:9266485
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项目类别:
-
资助金额:$39.63万
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财政年份:2015
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负责人:Ganapati Holanagadde Mahabaleshwar
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依托单位:
Role of KLF6 in myeloid cell biology
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批准号:8910985
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项目类别:
-
资助金额:$39.63万
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财政年份:2014
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负责人:Ganapati Holanagadde Mahabaleshwar
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依托单位:
KLF2 Mediated HIF-1 Regulation and Macrophage Activation
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批准号:8307111
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项目类别:
-
资助金额:$24.9万
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财政年份:2011
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负责人:Ganapati Holanagadde Mahabaleshwar
-
依托单位:
KLF2 Mediated HIF-1 Regulation and Macrophage Activation
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批准号:8505528
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项目类别:
-
资助金额:$23.7万
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财政年份:2011
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负责人:Ganapati Holanagadde Mahabaleshwar
-
依托单位:
KLF2 Mediated HIF-1 Regulation and Macrophage Activation
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批准号:7713630
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项目类别:
-
资助金额:$9.0万
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财政年份:2009
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负责人:Ganapati Holanagadde Mahabaleshwar
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依托单位:
海外基金