The Role of Notch2 and Notch3 in Cutaneous Wound Healing
Notch2 和 Notch3 在皮肤伤口愈合中的作用
基本信息
- 批准号:9113952
- 负责人:
- 金额:$ 19.53万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2013
- 资助国家:美国
- 起止时间:2013-08-06 至 2018-07-31
- 项目状态:已结题
- 来源:
- 关键词:AdultAreaAwardBasic ScienceBiologyCessation of lifeClinicalComplexCountryCutaneousDataDevelopmentEnsureEnvironmentEpidermisEthicsEventExtracellular MatrixFacultyFamilyFamily memberFoundationsFundingGoalsHealedHealthHospitalizationHumanInfectionInstitutionKnockout MiceLeadLeadershipLigandsMediator of activation proteinMentorsMentorshipModelingMolecularMusOperative Surgical ProceduresPathway interactionsPlayPositioning AttributeProcessPublishingRegulationResearchResearch PersonnelResourcesRiskRoleScientistSeriesSignal TransductionSkinStratificationSurgeonTherapeuticTherapeutic InterventionTimeTissuesTrainingUnited StatesUniversitiesWisconsinWorkWound Healingbasecareercareer developmentcell typeclinically relevantdesigndirected attentionexpectationhealingimprovedin vivoinnovationinsightkeratinocyte differentiationmeetingsmonolayernotch proteinnovelnovel strategiesprogramsregenerative therapyskillstherapy developmenttissue regenerationwound
项目摘要
DESCRIPTION (provided by applicant): Candidate: My career goals are to become a leader in the study of wound healing and the development of regenerative therapies for cutaneous wounds. To achieve this I will undergo intensive training in the basic sciences in cutaneous biology and notch signaling as well as ethics in the conduct of research. This will include formal coursework, one-on-one mentorship, presentations at lab meetings, department and University-wide seminars and national meetings. I will lead a nascent team of investigators in the study of cutaneous biology to develop a scientific foundation for understanding the mechanisms of cutaneous wound healing. I will submit an RO1 application no later than year 4 of the award period. Finally, I will seek leadership positions in national organizations in order to enhance collaborative efforts in this area as well as direct attention and resources towards developing therapies and solutions for this problem. All of these steps will facilitate my successful transitin to independence. Environment: The University of Wisconsin is one of the premier research institutions in the United States with over 800 biologists on campus. The Department of Surgery enjoys a reputation as one of the top in the country in terms of federal funding and career development of surgeon-scientists. The Department has mobilized its significant resources in making a commitment to Dr. King's career development including guarantees for start-up funds ($220,000) and 9 months of protected time per year. In addition, Dr. King will be mentored by two exceptional scientists and very successful mentors on this campus (Drs. Allen-Hoffmann and Chen) as well as other outstanding faculty. These components will provide him with an optimal research environment that will ensure that his transition to independence is successful. Research: My long-term goal is to develop an independent research career as a clinician scientist focused on the development of novel and effective therapeutic interventions for the treatment of cutaneous wounds. The objective of this application is to determine the molecular mechanism of the Notch family in human and murine cutaneous wound healing. Our central hypothesis is that skin specific Notch family members play a significant role in cutaneous wound healing by differential regulation of proliferation, keratinocyte differentiation and stratificatio within the epidermis. We have developed this hypothesis based upon our preliminary data and the published work of Kopan, Dotto, Radtke, Fuchs and others The rationale for the proposed research program is that it expected to yield new insights into the molecular mechanisms of cutaneous wound healing through which a clinically relevant therapeutic intervention could be developed for the treatment of cutaneous wounds, while at the same time, providing me the means of establishing independence as a clinician scientist. We are well prepared to pursue these studies because of the commitment of our institution to develop both novel strategies for wound healing and independent clinician scientists. I have created a mentoring team and collaborators with all of the skills needed to guide me in my pursuit to gain an independent research program. We will achieve our objectives through the pursuit of the following specific aims: Specific Aim #1: Investigate the role of the Notch family in cutaneous wound healing utilizing chimeric K14 specific Notch1, 2, or 3 knockout mice. Our working hypothesis is that wounds created in K14 specific Notch knockout mice have decreased rates of closure and decreased barrier function. Specific Aim #2: Characterize the role of the Notch family in cutaneous wound closure and establishment of barrier function in wound healing modeled in monolayer and organotypic culture. Our working hypothesis is that inhibition of the notch pathway will lead to delayed closure, and decreased barrier function in wounds and that re-activation of the notch pathway will increase the rate of closure and improve the barrier function of the "healed" organotypic skin. Specific Aim #3: Characterize the ability of notch activation to
heal in vivo wounds utilizing chimeric K14 specific Notch1, 2, or 3 knockout mice. Our working hypothesis is that activating notch will increase the rate of closure and improve the barrier function of the wounded skin.
候选人:我的职业目标是成为伤口愈合研究和皮肤伤口再生疗法发展的领导者。为了实现这一目标,我将接受皮肤生物学和notch信号的基础科学以及研究伦理方面的强化训练。这将包括正式的课程,一对一的指导,在实验室会议上的演讲,系和全校范围的研讨会和全国会议。我将带领一个新生的研究团队进行皮肤生物学的研究,为理解皮肤伤口愈合的机制奠定科学基础。我将不迟于奖励期的第四年提交RO1申请。最后,我将在国家组织中寻求领导职位,以加强这一领域的合作努力,并直接关注和资源,以开发针对这一问题的治疗和解决方案。所有这些步骤将有助于我成功过渡到独立。环境:威斯康星大学是美国首屈一指的研究机构之一,在校园里有800多名生物学家。在联邦资助和外科科学家的职业发展方面,外科部门享有全国顶尖的声誉。新闻部调动了大量资源,对金博士的职业发展作出承诺,包括保证启动资金(22万美元)和每年9个月的受保护时间。此外,金博士还将受到该校两位杰出的科学家和非常成功的导师的指导。Allen-Hoffmann和Chen)以及其他杰出的教师。这些因素将为他提供一个最佳的研究环境,以确保他成功过渡到独立。研究:我的长期目标是发展独立的研究事业,作为一名临床医生科学家,专注于开发新颖有效的皮肤伤口治疗干预措施。本应用的目的是确定Notch家族在人类和小鼠皮肤伤口愈合中的分子机制。我们的中心假设是,皮肤特异性Notch家族成员通过对表皮内增殖、角质细胞分化和分层的差异调节,在皮肤伤口愈合中发挥重要作用。根据我们的初步数据和Kopan、Dotto、Radtke、Fuchs等人发表的研究成果,我们提出了这一假设。提出这项研究计划的基本原理是,它有望对皮肤伤口愈合的分子机制产生新的见解,通过这种机制,可以为皮肤伤口的治疗开发出临床相关的治疗干预措施,同时,为我提供建立独立的临床医生科学家的手段。我们已经做好了充分的准备来进行这些研究,因为我们机构致力于开发伤口愈合的新策略和独立的临床医生科学家。我创建了一个指导团队和合作者,他们拥有指导我获得独立研究项目所需的所有技能。我们将通过追求以下具体目标来实现我们的目标:具体目标#1:利用嵌合K14特异性Notch1、2或3敲除小鼠研究Notch家族在皮肤伤口愈合中的作用。我们的工作假设是,在K14特异性Notch敲除小鼠中产生的伤口愈合率降低,屏障功能降低。具体目标#2:描述Notch家族在皮肤伤口闭合中的作用,以及在单层和器官型培养中伤口愈合模型中屏障功能的建立。我们的工作假设是,缺口通路的抑制将导致伤口的延迟闭合和屏障功能的下降,而缺口通路的重新激活将增加闭合的速度,并改善“愈合”的器官型皮肤的屏障功能。具体目标#3:描述notch激活的能力
项目成果
期刊论文数量(0)
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Timothy W King其他文献
Timothy W King的其他文献
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{{ truncateString('Timothy W King', 18)}}的其他基金
The Role of Notch2 and Notch3 in Cutaneous Wound Healing
Notch2 和 Notch3 在皮肤伤口愈合中的作用
- 批准号:
9342947 - 财政年份:2013
- 资助金额:
$ 19.53万 - 项目类别:
The Role of Notch2 and Notch3 in Cutaneous Wound Healing
Notch2 和 Notch3 在皮肤伤口愈合中的作用
- 批准号:
8581590 - 财政年份:2013
- 资助金额:
$ 19.53万 - 项目类别:
The Role of Notch2 and Notch3 in Cutaneous Wound Healing
Notch2 和 Notch3 在皮肤伤口愈合中的作用
- 批准号:
8891446 - 财政年份:2013
- 资助金额:
$ 19.53万 - 项目类别:
The Role of Notch2 and Notch3 in Cutaneous Wound Healing
Notch2 和 Notch3 在皮肤伤口愈合中的作用
- 批准号:
9332985 - 财政年份:2013
- 资助金额:
$ 19.53万 - 项目类别:
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