Animal Models and Tissue Engineering Core The skin is a complex organ that undergoes life-long renewal through spatially programmed growth and differentiation. It is composed of many distinct cell types (epithelial, fibroblast, endothelial, adipose, immune, neurons, etc.) that work in concert to allow normal physiology or that are disrupted to yield pathologies. Both normal and disease states of the skin are characterized by a specific three-dimensional architecture and interactions between these cell types which cultured cells in isolation cannot fully recapitulate. A critical aspect of basic and translational research involves the generation and application of skin tissue and animal models with an intact epidermal permeability barrier and physiologic connections to the systemic circulation. The goal of the Animal Models and Tissue Engineering Core is to provide consultation, generation and data analyses of a broad range of animal and skin tissue models. These include 1) 3-D organotypic skin culture, 2) de novo human skin regeneration on immunodeficient mice with genetically modified human epidermal and dermal cells, 3) lesional or normal human skin xenotransplantation onto immunodeficient mice, 4) various surgical and physiological wound healing models of mouse and swine, and 5) mouse models with skin cell targeted genetic engineering. These models will be tailored towards the specific needs of each investigator for functional, mechanistic and pharmacological studies. Our service will be provided through team efforts of basic science researchers, dermatologists and surgeons. These core resources will not only strengthen the investigations of current skin but also facilitate entry into skin research for other investigators who lack the technical basis to initiate such effort given a historical focus in other systems. We are confident that Duke research community has a strong desire and an enormous capacity to expand its skin disease-focused research.

Public Health Relevance

Healthy and diseased skin involves a complex, three-dimensional structure composed of a wide variety of cell types. In order to increase the potential clinical relevance of basic and pre-clinical research in skin biology and disease, this Core will provide consultation, generation, and data analysis of animal and skin tissue models that demonstrate this three-dimensional structure.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Center Core Grants (P30)
Project #
5P30AR066527-02
Application #
8900965
Study Section
Special Emphasis Panel (ZAR1-KM)
Project Start
Project End
Budget Start
2015-08-01
Budget End
2016-07-31
Support Year
2
Fiscal Year
2015
Total Cost
$150,319
Indirect Cost
$55,779
Name
Duke University
Department
Type
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Klann, Tyler S; Crawford, Gregory E; Reddy, Timothy E et al. (2018) Screening Regulatory Element Function with CRISPR/Cas9-based Epigenome Editing. Methods Mol Biol 1767:447-480
Klann, Tyler S; Black, Joshua B; Gersbach, Charles A (2018) CRISPR-based methods for high-throughput annotation of regulatory DNA. Curr Opin Biotechnol 52:32-41
Chen, Yong; Moore, Carlene D; Zhang, Jennifer Y et al. (2017) TRPV4 Moves toward Center-Fold in Rosacea Pathogenesis. J Invest Dermatol 137:801-804
Polstein, Lauren R; Juhas, Mark; Hanna, Gabi et al. (2017) An Engineered Optogenetic Switch for Spatiotemporal Control of Gene Expression, Cell Differentiation, and Tissue Morphogenesis. ACS Synth Biol 6:2003-2013
Suwanpradid, Jutamas; Holcomb, Zachary E; MacLeod, Amanda S (2017) Emerging Skin T-Cell Functions in Response to Environmental Insults. J Invest Dermatol 137:288-294
Liu, Xinjian; Li, Fang; Huang, Qian et al. (2017) Self-inflicted DNA double-strand breaks sustain tumorigenicity and stemness of cancer cells. Cell Res 27:764-783
Klann, Tyler S; Black, Joshua B; Chellappan, Malathi et al. (2017) CRISPR-Cas9 epigenome editing enables high-throughput screening for functional regulatory elements in the human genome. Nat Biotechnol 35:561-568
Zhang, Xiaoling; Luo, Suju; Wu, Joseph et al. (2017) KIND1 Loss Sensitizes Keratinocytes to UV-Induced Inflammatory Response and DNA Damage. J Invest Dermatol 137:475-483
Ousterout, David G; Gersbach, Charles A (2016) The Development of TALE Nucleases for Biotechnology. Methods Mol Biol 1338:27-42
Li, Fang; Liu, Xinjian; Sampson, John H et al. (2016) Rapid Reprogramming of Primary Human Astrocytes into Potent Tumor-Initiating Cells with Defined Genetic Factors. Cancer Res 76:5143-50

Showing the most recent 10 out of 26 publications