A Study of Biological Function of Basonuclin
A Study of Biological Function of Basonuclin
批准号:
7911749
负责人:
GEORGE COTSARELIS
金额:
$39.6万
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:
2009-08-10 至 2012-07-31
关键词:
AffectAreaArtsBasal cell carcinomaBiochemicalBiochemical PathwayBioinformaticsBiologicalBiological AssayBiological ProcessBiologyCell AdhesionCell Differentiation processCell ProliferationCell physiologyCellsCloningCodeComplexCutaneousDNADNA Polymerase IDNA Polymerase IIDNA-Directed RNA PolymeraseDataDefectDevelopmentEmergency SituationEpidermal Growth Factor ReceptorEpidermisEpithelialEpitheliumEquilibriumExhibitsFundingGLI Family ProteinGLI2 geneGene ExpressionGene TargetingGenesGenetic TranscriptionGenomicsGoalsHairHair follicle structureHealedHomeostasisIn VitroInjuryKnock-outKnockout MiceKnowledgeLeadLightLinkMAP Kinase GeneMAPK14 geneMaintenanceMalignant NeoplasmsMediatingModelingMolecularMolecular ProfilingMonitorMovementMusMutant Strains MiceMutationNatural regenerationNeoplastic Cell TransformationOnline Mendelian Inheritance In ManPathway interactionsPhenotypeProcessProteinsRNA Polymerase IRecombinant DNAResearchRibosomal RNARoleSignal TransductionSkinSkin CancerStem cellsStratified EpitheliumStructureTechniquesTestingThickTimeTissuesTranscriptTransforming Growth Factor alphaTumor Necrosis Factor-alphaUp-RegulationVariantWound HealingZinc Fingersbasebasonuclinbeta catenincancer cellcell typecorneal epitheliumhealinghuman TNF proteinin vivoinhibitor/antagonistkeratinocytemRNA Expressionmigrationmouse modelnovelnovel therapeutic interventionnull mutationpromoterrRNA Genesreceptorrepairedresponserestorationskin disorderskin regenerationsmoothened signaling pathwaystem cell biologytissue regenerationtranscription factortumorigenesiswound
中文摘要
我们的长期目标是了解核素基因在皮肤和头发中的作用
英文摘要
Our long-term goal is to understand the role of the basonuclin gene in skin and hair
follicle biology. Basonuclin (BNC1) is a zinc finger protein found in abundance in the
keratinocytes of the epidermis and hair follicle. We believe that it coordinates activity of
other genes through transcription factor activity. Our biochemical and bioinformatic
studies show that BNC1 regulates transcription of genes in six different pathways. The
BNC1 regulatory network is linked to pathways such as EGFR, p38 MAPK and TGFalpha.
These genes control important cellular functions like proliferation, migration and
differentiation. BNC1 is up-regulated in basal cell carcinoma (BCC). Our study of a Bnc1
knock out model suggests that it is required for hair follicle regeneration after hairplucking,
and Bnc1-null mutation delays restoration of hair follicular stem cells after hairplucking.
In this proposal, we will evaluate the role of Bnc-1 and Bnc-2 in skin
regeneration, wound repair and hair follicle cycling. We will characterize how the Bnc1-
null mutation affects hair regeneration, including determination of which cellular
processes are affected by this mutation and what molecular perturbations are caused by
Bnc1-null mutation. By examining Bnc-1 and Bnc-2 single and double knockout mice, we
will assess the contribution of these genes to maintenance of epithelial stem cells in the
bulge as well as the response of these cells to injury. Using mice that we have
developed to study the fate of bulge stem cells, we will trace the movement and
contribution of bulge cells in the Bnc mutant mice following hair plucking and skin injury.
We will study the interaction of BNC with the EGFr pathway using mice with deleted
receptors or mice expressing inhibitors of the EGFr pathway. Changes in proliferation,
differentiation and migration will be assessed in both in vitro and in vivo assays.
Overall, our research will discern the effect of deleting Bnc-1 and Bnc-2 in the
cutaneous epithelium. The role of Bnc’s in the EGFr pathway will be discerned. The
studies will impact on understanding stem cell biology and the role of Bnc’s in wound
healing, hair cycling and skin regeneration.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Penn Resource-based Center to Support and Translate Skin DiseasesResearch
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批准号:9765154
-
项目类别:
-
资助金额:$76.05万
-
财政年份:2016
-
负责人:GEORGE COTSARELIS
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依托单位:
Interfollicular epidermal stem cells in human and mouse skin
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批准号:8149973
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项目类别:
-
资助金额:$17.28万
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财政年份:2010
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负责人:GEORGE COTSARELIS
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依托单位:
Interfollicular epidermal stem cells in human and mouse skin
-
批准号:8048827
-
项目类别:
-
资助金额:$21.6万
-
财政年份:2010
-
负责人:GEORGE COTSARELIS
-
依托单位:
A Study of Biological Function of Basonuclin
-
批准号:7579551
-
项目类别:
-
资助金额:$39.75万
-
财政年份:2009
-
负责人:GEORGE COTSARELIS
-
依托单位:
Hair follicle bulge cells in tumorigenesis and alopecia
-
批准号:7929359
-
项目类别:
-
资助金额:$25.2万
-
财政年份:2009
-
负责人:GEORGE COTSARELIS
-
依托单位:
Stem Cell and Xenografts
-
批准号:7678119
-
项目类别:
-
资助金额:$14.7万
-
财政年份:2009
-
负责人:GEORGE COTSARELIS
-
依托单位:
Hair Follicle Neogenesis in Response to Wounding
-
批准号:8097473
-
项目类别:
-
资助金额:$31.54万
-
财政年份:2007
-
负责人:GEORGE COTSARELIS
-
依托单位:
Hair follicle neogenesis in response to wounding
-
批准号:8505685
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项目类别:
-
资助金额:$34.0万
-
财政年份:2007
-
负责人:GEORGE COTSARELIS
-
依托单位:
Hair Follicle Neogenesis in Response to Wounding
-
批准号:7640612
-
项目类别:
-
资助金额:$33.19万
-
财政年份:2007
-
负责人:GEORGE COTSARELIS
-
依托单位:
Hair Follicle Neogenesis in Response to Wounding
-
批准号:7777040
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项目类别:
-
资助金额:$15.9万
-
财政年份:2007
-
负责人:GEORGE COTSARELIS
-
依托单位:
Hair Follicle Neogenesis in Response to Wounding
-
批准号:7880861
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项目类别:
-
资助金额:$32.85万
-
财政年份:2007
-
负责人:GEORGE COTSARELIS
-
依托单位:
Hair Follicle Neogenesis in Response to Wounding
-
批准号:7303193
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项目类别:
-
资助金额:$33.86万
-
财政年份:2007
-
负责人:GEORGE COTSARELIS
-
依托单位:
Hair Follicle Neogenesis in Response to Wounding
-
批准号:7468494
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项目类别:
-
资助金额:$33.19万
-
财政年份:2007
-
负责人:GEORGE COTSARELIS
-
依托单位:
Hair follicle neogenesis in response to wounding
-
批准号:8708760
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项目类别:
-
资助金额:$34.0万
-
财政年份:2007
-
负责人:GEORGE COTSARELIS
-
依托单位:
Transgenic Mouse Model for Barrett's Esophagus
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批准号:6665306
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项目类别:
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资助金额:$15.85万
-
财政年份:2002
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负责人:GEORGE COTSARELIS
-
依托单位:
Transgenic Mouse Model for Barrett's Esophagus
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批准号:6577587
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项目类别:
-
资助金额:$15.85万
-
财政年份:2002
-
负责人:GEORGE COTSARELIS
-
依托单位:
Hair follicle bulge cells in tumorigenesis and alopecia
-
批准号:7120984
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项目类别:
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资助金额:$11.6万
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财政年份:2000
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负责人:GEORGE COTSARELIS
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依托单位:
Hair follicle bulge cells in tumorigenesis and alopecia
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批准号:6968801
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项目类别:
-
资助金额:$34.54万
-
财政年份:2000
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负责人:GEORGE COTSARELIS
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依托单位:
Hair follicle bulge cells in tumorigenesis and alopecia
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批准号:7640613
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项目类别:
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资助金额:$32.2万
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财政年份:2000
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负责人:GEORGE COTSARELIS
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依托单位:
Hair follicle bulge cells in tumorigenesis and alopecia
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批准号:7424144
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项目类别:
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资助金额:$14.96万
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财政年份:2000
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负责人:GEORGE COTSARELIS
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