The unifying theme of this program is the Biology of the Cutaneous Epithelium, a term inclusive of the epidermis and the follicular epithelium. This Program is composed of five projects, each headed by established investigators, and three cores. The five component projects focus on distinct, yet related aspects of skin biology, and all projects are designed to study fundamental cellular mechanisms controlling cell differentiation, maintenance of tissue structure, and response to injury. Furthermore, this Program includes investigators outside of Dermatology, thereby broadening the scientific foundation of skin-related research at Washington University. The Program begins with studies on skin development and cellular differentiation. Dr. Raphael Kopan (Project 1) will study the role of Notch and related cell-signaling molecules during stages of cell-fate determination and differentiation of the developing and the nature, cycling hair follicle. Dr. David Ornitz (Project 2) proposes to study the functional and biochemical interactions of fibroblast growth factor-10 (FGF-10), which is produced in the dermis, and its receptor on keratinocytes during development and in response to injury. The molecular determinants required for formation of desmosomes and their role in keratinocyte signaling and epidermal morphogenesis will be addressed by Dr. Sergey Troyanovsky (Project 3). For Project 4, Dr. William Parks will determine the precise and distinct cell-matrix interactions that regulate the activation, maintenance, and deactivation of keratinocytes in response to wounding and how these events control expression of wound-related genes. Dr. Michael Caparon (Project 5) focuses on how group A streptococcus interact with the epidermis and how keratinocytes respond to and defend against bacterial infection. Three Cores will support the effort of the Program investigators. The Administrative Core (Core A) will be responsible for Program management and coordination. The Transgenic Core (Core B) will create genetically- defined animals (e.g., knock-outs, conditional knock-outs, transgenics) for all Program investigators, and in situ hybridizations for all projects. Thus, this new Program is integrated around a common scientific theme and goal, thereby promoting many interactions, and is supported by scientific cores.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Program Projects (P01)
Project #
5P01AR045254-02
Application #
2899932
Study Section
Special Emphasis Panel (ZAR1-AAA-C (J1))
Program Officer
Moshell, Alan N
Project Start
1998-05-10
Project End
2003-03-31
Budget Start
1999-04-01
Budget End
2000-03-31
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Washington University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Klingelhofer, Jorg; Troyanovsky, Regina B; Laur, Oscar Y et al. (2003) Exchange of catenins in cadherin-catenin complex. Oncogene 22:1181-8
Lin, Meei-Hua; Kopan, Raphael (2003) Long-range, nonautonomous effects of activated Notch1 on tissue homeostasis in the nail. Dev Biol 263:343-59
Liu, Zhonghao; Xu, Jingsong; Colvin, Jennifer S et al. (2002) Coordination of chondrogenesis and osteogenesis by fibroblast growth factor 18. Genes Dev 16:859-69
Klingelhofer, Jorg; Laur, Oscar Y; Troyanovsky, Regina B et al. (2002) Dynamic interplay between adhesive and lateral E-cadherin dimers. Mol Cell Biol 22:7449-58
Neely, Melody N; Pfeifer, John D; Caparon, Michael (2002) Streptococcus-zebrafish model of bacterial pathogenesis. Infect Immun 70:3904-14
Kopan, Raphael; Lee, Jonghyeob; Lin, Meei-Hua et al. (2002) Genetic mosaic analysis indicates that the bulb region of coat hair follicles contains a resident population of several active multipotent epithelial lineage progenitors. Dev Biol 242:44-57
Lyon, W R; Madden, J C; Levin, J C et al. (2001) Mutation of luxS affects growth and virulence factor expression in Streptococcus pyogenes. Mol Microbiol 42:145-57
Madden, J C; Ruiz, N; Caparon, M (2001) Cytolysin-mediated translocation (CMT): a functional equivalent of type III secretion in gram-positive bacteria. Cell 104:143-52
Xu, J; Clark, R A; Parks, W C (2001) p38 mitogen-activated kinase is a bidirectional regulator of human fibroblast collagenase-1 induction by three-dimensional collagen lattices. Biochem J 355:437-47
Dumin, J A; Dickeson, S K; Stricker, T P et al. (2001) Pro-collagenase-1 (matrix metalloproteinase-1) binds the alpha(2)beta(1) integrin upon release from keratinocytes migrating on type I collagen. J Biol Chem 276:29368-74

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