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过程中的作用，并为主要研究者Anne Hocking提供必要的科学工具和职业发展，以成功地成为伤口愈合领域的独立研究者。在接下来的三年里，霍金博士将遵循一项研究职业发展计划，该计划包括独立研究人员所需职业技能的教育课程计划和在由Frank Isik博士（导师），Randall Moon博士（导师），以及华盛顿大学的Nicole Gibran博士（顾问）和Fred哈钦森癌症研究中心的William Carter博士（顾问）。成年哺乳动物的皮肤伤口愈合是不完美的。愈合的皮肤缺乏表皮附属物，如毛囊，汗液和皮脂腺，这可能导致热调节和干燥的问题。疤痕也可以毁容，降低抗张强度，并导致收缩，这可能会限制流动性。此外，异常的伤口愈合可引起并发症，如肥厚性瘢痕和无法愈合的慢性伤口。为了开发改善成人伤口愈合的疗法，有必要了解皮肤伤口愈合期间细胞信号传导途径在细胞增殖、迁移和新细胞外基质生物合成的协调中的作用。因此，Dr. Hocking提出解决伤口愈合期间Wnt-4信号传导上调的功能后果，具有以下具体目标：1）确定皮肤伤口愈合期间Wnt-4表达的时间和空间调节; 2）确定Wnt-4是否调节皮肤伤口修复期间真皮成纤维细胞增殖、迁移和细胞外基质的生物合成;和3）确定Wnt-4是否调节皮肤伤口中的角质形成细胞增殖和迁移。这项应用的意义在于，它将提高我们对细胞信号传导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.