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. [unreadable] [unreadable] [unreadable]