This is a proposal for continuation of an interdisciplinary program for basic research in problems of skin biology and pathology consisting of five projects and a core laboratory. 1. Investigation of the biochemical control of the complex pathway of filaggrin synthesis and the function of filaggrin in its interaction with keratin filaments composed of specific keratin proteins in normal epidermis and in patients with disorders of keratinization resulting from single gene abnormalities. 2. Gain further understanding of the inherited diseases of collagen metabolism by defining mutations in the types I and III collagen genes which produce the phenotypes of several types of OI, EDS, and Marfan's Syndrome and by determining how the mutations alter processing of these collagens by cultured cells from patients with these diseases. 3. Analyze the acoustic microscope (SLAM) properties of skin and healing wounds as well as articular cartilage and aorta. These measurements will be compared to structural analysis, tensile strength measurements, biochemical analysis of collagens, elastin and proteoglycan analysis. Compare the acoustical properties as measured by SLAM with backscattered acoustical properties (BAT) of the same tissues to establish a technology clinically applicable for assessment of human wound repair. 4. Investigate the regulation of epidermal differentiation in human keratinocytes cultured from normal and ichthyotic subjects. Using biochemical and morphologic markers of differentiation and cDNA clones for profilaggrin. 5. Investigate the structure, syntheses and function of proteoglycans (PG) and glycosaminoglycans (GAG) and collagen in dermal and aortic connective tissue and cells from normal subjects and will perform comparable assays of the mutations occurring in Marfan's Syndrome.
| Bunick, Christopher G; Presland, Richard B; Lawrence, Owen T et al. (2015) Crystal Structure of Human Profilaggrin S100 Domain and Identification of Target Proteins Annexin II, Stratifin, and HSP27. J Invest Dermatol 135:1801-1809 |
| Chan, Aegean; Godoy-Gijon, Elena; Nuno-Gonzalez, Almudena et al. (2015) Cellular basis of secondary infections and impaired desquamation in certain inherited ichthyoses. JAMA Dermatol 151:285-92 |
| Mitchell, Anna L; Judis, LuAnn M; Schwarze, Ulrike et al. (2012) Characterization of tissue-specific and developmentally regulated alternative splicing of exon 64 in the COL5A1 gene. Connect Tissue Res 53:267-76 |
| Chatterjea, Sudeshna M; Resing, Katheryn A; Old, William et al. (2011) Optimization of filaggrin expression and processing in cultured rat keratinocytes. J Dermatol Sci 61:51-9 |
| Mitchell, Anna L; Schwarze, Ulrike; Jennings, Jessica F et al. (2009) Molecular mechanisms of classical Ehlers-Danlos syndrome (EDS). Hum Mutat 30:995-1002 |
| Abrass, C K; Berfield, A K; Ryan, M C et al. (2006) Abnormal development of glomerular endothelial and mesangial cells in mice with targeted disruption of the lama3 gene. Kidney Int 70:1062-71 |
| Pirrone, Annalisa; Hager, Barbara; Fleckman, Philip (2005) Primary mouse keratinocyte culture. Methods Mol Biol 289:3-14 |
| Presland, Richard B; Fleckman, Philip (2005) Tetracycline-regulated gene expression in epidermal keratinocytes. Methods Mol Biol 289:273-86 |
| Kelsell, David P; Norgett, Elizabeth E; Unsworth, Harriet et al. (2005) Mutations in ABCA12 underlie the severe congenital skin disease harlequin ichthyosis. Am J Hum Genet 76:794-803 |
| Frank, Diane E; Carter, William G (2004) Laminin 5 deposition regulates keratinocyte polarization and persistent migration. J Cell Sci 117:1351-63 |
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