Ineffective wound healing responses enable chronic radiation-induced salivary gland dysfunction
无效的伤口愈合反应会导致慢性辐射引起的唾液腺功能障碍
基本信息
- 批准号:10678634
- 负责人:
- 金额:$ 34.71万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-09-20 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAddressApicalBiologyBiopsyCellsChronicClinicClinicalComplexCuesDataDefectDetectionEffectivenessEpitheliumEquilibriumFailureFunctional disorderGenetically Engineered MouseGlandGoalsHead and Neck CancerInflammationInflammatoryInterventionLiteratureMacrophageMediatorModelingMolecularNatural regenerationNuclearNuclear TranslocationOutcomePathway interactionsPatientsPhasePhenotypePhysiologicalPlayPopulation HeterogeneityPre-Clinical ModelProcessProductionProliferatingQuality of lifeRadiationRadiation induced damageRadiation therapyRegulationResolutionRoleSalivaSalivarySalivary GlandsSamplingSeriesSignal InductionStratificationTechnologyTestingTherapeuticTimeTissuesTranscription CoactivatorUndifferentiatedValidationVisionWorkWound modelsXerostomiacancer therapycell typechronic woundcommon treatmentcytokinehead and neck cancer patienthealingmouse modelnovel therapeuticspharmacologicpre-clinicalpreventreconstitutionrepairedresponserestorationside effectstandard of carestem cellswound healing
项目摘要
Abstract:
More than 73% of head and neck cancer patients continue to suffer from the chronic consequences of
xerostomia months to years after the completion of radiotherapy making this one of the most compelling
issues in salivary gland biology. Despite technological advancements in cancer therapies, collateral
damage to salivary glands remains a significant problem for these patients and severely diminishes
their quality of life. The field of radiation-induced salivary gland damage is severely hampered by the
lack of a comprehensive model detailing the molecular stages of damage. The overall vision is to
restore salivary gland function in patients following radiotherapy by identifying healing stages in salivary
glands that lead to the stratification and administration of precise therapeutics for their stage. This
proposal will use the sequential phases of wound healing involving inflammation to its resolution and
reconstitution of tissue through proliferation and differentiation of epithelial tissue as steps to
accomplish this vision. We hypothesize that irradiated salivary glands fail to efficiently progress
through the wound healing phases leading to prolonged dysfunction. Our prior work has demonstrated
that radiation-induced proliferation in salivary glands is due in part to disruption of the PKCζ apical
polarity complex leading to enhanced nuclear localization of Yap, while models that restore salivary
function have repaired apical polarity and reduced nuclear localization of Yap. We propose to develop
a model that integrates each phase of wound healing detailing the interactions between phases and
the impact of nuclear Yap on the progression through these phases. The outcomes from this work
include: 1) inputs regulating sustained Yap nuclear translocation, 2) ability of chronic nuclear Yap to
prevent re-differentiation after IR, 3) when/if Yap is necessary for restoration of salivary gland function,
4) uncovering the interplay between wound healing phases that prevent restoration of salivary gland
function. Understanding this process would have a positive impact by revealing intervention points that
promote restoration of salivary gland function.
文摘:
项目成果
期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Evaluating the transcriptional landscape and cell-cell communication networks in chronically irradiated parotid glands.
- DOI:10.1016/j.isci.2023.106660
- 发表时间:2023-05-19
- 期刊:
- 影响因子:5.8
- 作者:Rheinheimer, Brenna A.;Pasquale, Mary C.;Limesand, Kirsten H.;Hoffman, Matthew P.;Chibly, Alejandro M.
- 通讯作者:Chibly, Alejandro M.
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KIRSTEN H LIMESAND其他文献
KIRSTEN H LIMESAND的其他文献
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{{ truncateString('KIRSTEN H LIMESAND', 18)}}的其他基金
Metabolic dysregulation during radiation-induced salivary gland dysfunction
辐射引起的唾液腺功能障碍期间的代谢失调
- 批准号:
10254415 - 财政年份:2020
- 资助金额:
$ 34.71万 - 项目类别:
Ineffective wound healing responses enable chronic radiation-induced salivary gland dysfunction
无效的伤口愈合反应会导致慢性辐射引起的唾液腺功能障碍
- 批准号:
10221671 - 财政年份:2019
- 资助金额:
$ 34.71万 - 项目类别:
Ineffective wound healing responses enable chronic radiation-induced salivary gland dysfunction
无效的伤口愈合反应会导致慢性辐射引起的唾液腺功能障碍
- 批准号:
10022119 - 财政年份:2019
- 资助金额:
$ 34.71万 - 项目类别:
Ineffective wound healing responses enable chronic radiation-induced salivary gland dysfunction
无效的伤口愈合反应会导致慢性辐射引起的唾液腺功能障碍
- 批准号:
10457942 - 财政年份:2019
- 资助金额:
$ 34.71万 - 项目类别:
Mechanisms of IGF-1 mediated rescue of radiation-induced salivary gland dysfuncti
IGF-1介导的拯救辐射引起的唾液腺功能障碍的机制
- 批准号:
7900030 - 财政年份:2008
- 资助金额:
$ 34.71万 - 项目类别:
Mechanisms of IGF-1 mediated rescue of radiation-induced salivary gland dysfuncti
IGF-1介导的放射诱导唾液腺功能障碍的挽救机制
- 批准号:
7530790 - 财政年份:2008
- 资助金额:
$ 34.71万 - 项目类别:
Mechanisms of IGF-1 mediated rescue of radiation-induced salivary gland dysfuncti
IGF-1介导的拯救辐射引起的唾液腺功能障碍的机制
- 批准号:
8288027 - 财政年份:2008
- 资助金额:
$ 34.71万 - 项目类别:
Mechanisms of IGF-1 mediated rescue of radiation-induced salivary gland dysfuncti
IGF-1介导的放射诱导唾液腺功能障碍的挽救机制
- 批准号:
7879108 - 财政年份:2008
- 资助金额:
$ 34.71万 - 项目类别:
Mechanisms of IGF-1 mediated rescue of radiation-induced salivary gland dysfuncti
IGF-1介导的放射诱导唾液腺功能障碍的挽救机制
- 批准号:
8111787 - 财政年份:2008
- 资助金额:
$ 34.71万 - 项目类别:
Mechanisms of IGF-1 mediated rescue of radiation-induced salivary gland dysfuncti
IGF-1介导的放射诱导唾液腺功能障碍的挽救机制
- 批准号:
7663151 - 财政年份:2008
- 资助金额:
$ 34.71万 - 项目类别:
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