The role of Wnt-4 signaling during cutaneous wound healing

描述（由申请人提供）：该项目的目标是深入了解Wnt-4信号在皮肤伤口愈合中的作用，并为首席研究员Anne Hocking提供作为伤口愈合领域独立研究者成功职业所需的科学工具和职业发展。在接下来的三年里，霍金博士将遵循一个研究职业发展计划，包括一个独立研究人员所需的职业技能教育课程和一个实验室研究项目，该项目由华盛顿大学的Frank Isik博士（导师）、Randall Moon博士（导师）、Nicole Gibran博士（顾问）和Fred Hutchinson癌症研究中心的William Carter博士（顾问）组成的咨询委员会指导。成年哺乳动物的皮肤伤口愈合是不完善的。愈合后的皮肤缺少表皮附属物，如毛囊、汗腺和皮脂腺，这些附属物会导致热调节和干燥问题。疤痕也会毁容，降低抗拉强度并导致收缩，这可能会限制活动能力。此外，伤口愈合异常会引起并发症，如肥厚性疤痕和慢性伤口无法愈合。为了开发改善成人创面愈合的治疗方法，有必要了解皮肤创面愈合过程中细胞信号通路在协调细胞增殖、迁移和新细胞外基质生物合成中的作用。因此，hockking博士提出解决伤口愈合过程中Wnt-4信号上调的功能后果，具体目的如下：1)确定皮肤伤口愈合过程中Wnt-4表达的时空调控；2)确定Wnt-4是否调控皮肤创面修复过程中真皮成纤维细胞的增殖、迁移和细胞外基质的生物合成；3)确定Wnt-4是否调节皮肤创面中角质细胞的增殖和迁移。这项应用的意义在于，它将提高我们对细胞信号如何协调伤口愈合所需的细胞过程的理解，并可能提出改善成人伤口愈合的新疗法。

DESCRIPTION (provided by applicant): The goals of this project are to gain insight into the role of Wnt-4 signaling during cutaneous wound healing and to provide the principal investigator, Anne Hocking with the scientific tools and career development necessary for a successful career as independent investigator in the field of wound healing. During the next three years, Dr. Hocking will follow a research career development plan consisting of a program of educational classes in career skills required for an independent researcher and a laboratory based research project under the guidance of a advisory committee comprised of Dr. Frank Isik (Mentor), Dr Randall Moon (Mentor), and Dr. Nicole Gibran (Advisor) at the University of Washington and Dr. William Carter (Advisor) at the Fred Hutchinson Cancer Research Center. Cutaneous wound healing is imperfect in adult mammals. Healed skin lacks epidermal appendages such as hair follicles, sweat and sebaceous glands which can result in problems with thermal regulation and desiccation. Scarring can also be disfiguring, diminish tensile strength and cause contraction which may limit mobility. In addition, abnormal wound healing can cause complications such as hypertrophic scarring and chronic wounds that fail to heal. In order to develop therapies to improve adult wound healing it is necessary to understand the role of cell signaling pathways in the coordination of cell proliferation, migration and biosynthesis of new extracellular matrix during cutaneous wound healing. Therefore, Dr. Hocking proposes to address the functional consequence of the up-regulation of Wnt-4 signaling during wound healing with the following specific aims: 1) determine the temporal and spatial regulation of Wnt-4 expression during cutaneous wound healing; 2) determine if Wnt-4 regulates dermal fibroblast proliferation, migration and biosynthesis of extracellular matrix during cutaneous wound repair; and 3) determine if Wnt-4 regulates keratinocyte proliferation and migration in the cutaneous wound. The significance of this application is that it will improve our understanding of how cell signaling coordinates the cellular processes required for wound healing and may suggest novel therapies to improve adult wound healing.