Abstract

The dominantly inherited form of dystrophic epidermolysis bullosa (DDEB), a mechano-bullous disease which presents blister with formation in the skin, is the result of dominant negative mutations in the type VII collagen gene (COL7A1). These mutations cause conformational changes in type VII collagen that interfere with the proper assembly of anchoring fibrills, important attachment structures of the cutaneous basement membrane zone. Currently, there is no available treatment option nor applicable in vivo experimental model for DDEB.
The aim of the proposed research is to establish an animal model for DDEB by expressing a type VII collagen construct in mice, that carries dominant negative mutations designed on the basis of COL7Al mutations in human DDEB patients. The in vivo models will be used to evaluate the feasibility of a novel treatment option, consisting of the utilization of hammerhead ribozymes to selectively eliminate mutant mRNA. The restoration of the normal phenotype will be followed using a number of qualitative and quantitative methods.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Center Core Grants (P30)
Project #
5P30AR044535-04
Application #
6346862
Study Section
Special Emphasis Panel (ZAR1-AAA-C (J2))
Project Start
1997-07-20
Project End
2001-06-30
Budget Start
Budget End
Support Year
4
Fiscal Year
2000
Total Cost
$77,307
Indirect Cost

  Institution

Name
Columbia University (N.Y.)
Department
Type
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032

  Publications

Shen, Yao; Stanislauskas, Milda; Li, Gen et al. (2017) Epigenetic and genetic dissections of UV-induced global gene dysregulation in skin cells through multi-omics analyses. Sci Rep 7:42646
Mathew, Grinu; Hannan, Abdul; Hertzler-Schaefer, Kristina et al. (2016) Targeting of Ras-mediated FGF signaling suppresses Pten-deficient skin tumor. Proc Natl Acad Sci U S A 113:13156-13161
Shen, Yao; Kim, Arianna L; Du, Rong et al. (2016) Transcriptome Analysis Identifies the Dysregulation of Ultraviolet Target Genes in Human Skin Cancers. PLoS One 11:e0163054
Dai, Zhenpeng; Xing, Luzhou; Cerise, Jane et al. (2016) CXCR3 Blockade Inhibits T Cell Migration into the Skin and Prevents Development of Alopecia Areata. J Immunol 197:1089-99
Abaci, Hasan E; Guo, Zongyou; Coffman, Abigail et al. (2016) Human Skin Constructs with Spatially Controlled Vasculature Using Primary and iPSC-Derived Endothelial Cells. Adv Healthc Mater 5:1800-7
Dainichi, Teruki; Hayden, Matthew S; Park, Sung-Gyoo et al. (2016) PDK1 Is a Regulator of Epidermal Differentiation that Activates and Organizes Asymmetric Cell Division. Cell Rep 15:1615-23
Johnson, Dylan; Mathur, Mohit C; Kobayashi, Tomoyoshi et al. (2016) The Cardiomyopathy Mutation, R146G Troponin I, Stabilizes the Intermediate ""C"" State of Regulated Actin under High- and Low-Free Ca(2+) Conditions. Biochemistry 55:4533-40
Shinkuma, Satoru; Guo, Zongyou; Christiano, Angela M (2016) Site-specific genome editing for correction of induced pluripotent stem cells derived from dominant dystrophic epidermolysis bullosa. Proc Natl Acad Sci U S A 113:5676-81
Kim, Arianna L; Back, Jung Ho; Zhu, Yucui et al. (2016) AKT1 Activation is Obligatory for Spontaneous BCC Tumor Growth in a Murine Model that Mimics Some Features of Basal Cell Nevus Syndrome. Cancer Prev Res (Phila) 9:794-802
Sun, Xiaoyun; Kim, Arianna; Nakatani, Masashi et al. (2016) Distinctive molecular responses to ultraviolet radiation between keratinocytes and melanocytes. Exp Dermatol 25:708-13

Showing the most recent 10 out of 130 publications