The skin of naked mole rats as a model for scar-free wound healing
裸鼹鼠皮肤作为无疤痕伤口愈合模型
基本信息
- 批准号:10238154
- 负责人:
- 金额:$ 38.98万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-09-01 至 2023-08-31
- 项目状态:已结题
- 来源:
- 关键词:3-DimensionalAddressAdultAffectAgingAnimal ModelAnimalsBiologyBiomedical ResearchBlood VesselsBostonBurn TraumaCandidate Disease GeneCardiovascular DiseasesCell CommunicationCellsChronicCicatrixClinicComplexContractureDataDefectDepositionDermalDevelopmentEmbryoEpigenetic ProcessEpithelialExhibitsExtracellular MatrixFibroblastsFibrosisGene Expression ProfileGenomeGrantGrowthHemostatic functionHeterocephalusHomeostasisHumanHuman BiologyHuman DevelopmentHuman GenomeHypertrophic CicatrixHypoxiaImmuneInflammationInjuryKeloidLaboratoriesLentivirusLongevityMaintenanceMalignant NeoplasmsMammalsMechanicsMediatingMesenchymalMesenchymeModelingModernizationMole RatsMusNatural regenerationNerve DegenerationNude MiceOperative Surgical ProceduresOryctolagus cuniculusOutcomeOutputPathologicPathologyPathway interactionsPatientsPharmacologyPhasePhysiologicalPhysiologyPopulationPreventionProcessProliferatingRattusResistanceRodentSalamanderSecureSignal TransductionSignaling ProteinSkinSkin graftSkin injurySkin repairSkin wound healingStudy modelsTestingTissuesTranslationsTransplantationUniversitiesVertebratesage relatedbasecomparativecostepidermal stem cellexperimental studygenome analysishealinghuman diseasein vitro Modelin vivoinnovationinsightkeratinocytenon-healing woundsnovelnovel therapeutic interventionporcine modelpreventpsychologicrecruitrepairedsingle-cell RNA sequencingskin regenerationskin woundstem cellstissue injurytissue repairtooltranscription factortranscriptometumorigenesiswoundwound healing
项目摘要
PROJECT SUMMARY
Skin repair after injury is a complex process that requires coordinate interactions between resident skin
cells, recruited immune cells and result in local tissue deposition/remodeling. Cell-cell interactions during wound
repair are regulated at several levels including signaling/transcription factor-mediated and epigenetic
mechanisms, while it remains unclear how these mechanisms are altered during pathological skin repair.
Hypertrophic scars commonly occur after burn, trauma or surgery, and are characterized by the excessive
deposition of extracellular matrix with the inadequate remodeling, which result in severe physiological and
psychological problems in patients. However, the effective prevention and treatment of the scars occurring as a
result of tissue injury are still limited, at least in part, due to the challenges in translation of the data obtained in
different animal (mouse, rabbit, pig) models to human skin and human skin scarring.
One of the fundamental questions in modern biomedical research is the search for new model organisms
that adequately reflect the mechanisms regulating human development, homeostasis and aging, as well as their
alterations in human diseases. Naked mole rats (NMRs, Heterocephalus glaber) are unique long-lived mammals
that possess marked resistance to cancer and other age-related pathologies and maintain sustained healthy life-
span span for up to 32 years, which is approximately ten-fold longer compared to mice or rats.
Comparative genome and transcriptome analyses revealed that the NMR genome show higher similarity
to the human genome compared to mice and rats. Our preliminary data demonstrate that NMRs also possess
the unique ability to regenerate skin wounds without scarring, thus suggesting them as the unique mammalian
model for studying mechanisms preventing scar formation after injury in adult skin.
In this exploratory grant, we will test a hypothesis that NMR skin serve as a unique model for studying
mechanisms of wound repair and scar formation. This hypothesis will be addressed via two Specific Aims (R61
phase) and relevance of the data obtained on NMRs will be further validated on human skin (R33 phase).
R61 phase: Aim 1. Characterize the NMR skin as innovative model for studying mechanisms of skin
regeneration and wound healing.
R61 phase: Aim 2. Define mechanisms contributing to scar-free wound healing in the NMR skin.
R33 phase: Aim 3. Validate the relevance of distinct regulatory mechanisms controlling the scar-
free wound repair process in the NMR skin to human skin.
The generated outputs from this application will provide novel insights into fundamental mechanisms
underlying scar formation after injury, enhance the innovative potential of securely establishing a place for the
NMR as a model organism for studying the biology of human skin, as well as will promote the development of
novel paradigms for modulation of wound healing and scar formation in humans.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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VLADIMIR A BOTCHKAREV其他文献
VLADIMIR A BOTCHKAREV的其他文献
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{{ truncateString('VLADIMIR A BOTCHKAREV', 18)}}的其他基金
Transposable elements in the keratinocyte genome and their regulation during skin development and epidermal differentiation
角质形成细胞基因组中的转座元件及其在皮肤发育和表皮分化过程中的调节
- 批准号:
10560618 - 财政年份:2021
- 资助金额:
$ 38.98万 - 项目类别:
Transposable elements in the keratinocyte genome and their regulation during skin development and epidermal differentiation
角质形成细胞基因组中的转座元件及其在皮肤发育和表皮分化过程中的调节
- 批准号:
10372905 - 财政年份:2021
- 资助金额:
$ 38.98万 - 项目类别:
The skin of naked mole rats as a model for scar-free wound healing
裸鼹鼠皮肤作为无疤痕伤口愈合模型
- 批准号:
10083984 - 财政年份:2020
- 资助金额:
$ 38.98万 - 项目类别:
The skin of naked mole rats as a model for scar-free wound healing
裸鼹鼠皮肤作为无疤痕伤口愈合模型
- 批准号:
10831130 - 财政年份:2020
- 资助金额:
$ 38.98万 - 项目类别:
DNA hydroxymethylation and Tet-enzymes in the control of the skin development and hair growth
DNA 羟甲基化和 Tet 酶在控制皮肤发育和毛发生长中的作用
- 批准号:
10641894 - 财政年份:2019
- 资助金额:
$ 38.98万 - 项目类别:
DNA hydroxymethylation and Tet-enzymes in the control of the skin development and hair growth
DNA 羟甲基化和 Tet 酶在控制皮肤发育和毛发生长中的作用
- 批准号:
10433970 - 财政年份:2019
- 资助金额:
$ 38.98万 - 项目类别:
DNA hydroxymethylation and Tet-enzymes in the control of the skin development and hair growth
DNA 羟甲基化和 Tet 酶在控制皮肤发育和毛发生长中的作用
- 批准号:
9982783 - 财政年份:2019
- 资助金额:
$ 38.98万 - 项目类别:
DNA hydroxymethylation and Tet-enzymes in the control of the skin development and hair growth
DNA 羟甲基化和 Tet 酶在控制皮肤发育和毛发生长中的作用
- 批准号:
10186705 - 财政年份:2019
- 资助金额:
$ 38.98万 - 项目类别:
Chromatin architectural protein CTCF and regulation of skin development and tumorigenesis
染色质结构蛋白 CTCF 与皮肤发育和肿瘤发生的调节
- 批准号:
9318763 - 财政年份:2017
- 资助金额:
$ 38.98万 - 项目类别:
Chromatin architectural protein CTCF and regulation of skin development and tumorigenesis
染色质结构蛋白 CTCF 与皮肤发育和肿瘤发生的调节
- 批准号:
9910061 - 财政年份:2017
- 资助金额:
$ 38.98万 - 项目类别:
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