A complex organ, skin is constantly renewing through the interactions of many distinct cell types. Understanding the interactions among these cell types is crucial to achieving complete understanding of the mechanisms of human skin disease and for development of effective new therapies. Important tools can accelerate cellular and mechanistic discoveries in skin biology and disease. These tools include advances in molecular technology that enable generation of genetically defined keratinocytes, fibroblasts and other cells relevant to skin disease. By coupling these approaches with techniques to create in vitro and in vivo human skin models, we can probe the functional effects of genetic modifications in both normal and diseased skin. To provide access to these and related technologies to advance discovery and translation in skin biology and disease, we propose creation of the Duke Skin Disease Research Core Center (SDRC). Our overall objective is to provide access to critical difficult-to-duplicate technologies and resources to facilitate studies at the gene, cellular, tisse and animal levels with relevance in understanding skin biology and pathogenesis of skin disease, and ultimately to facilitate development of new treatments for skin disease. We propose the following specific aims. 1) Establish a Cell and Gene Modification Core to support development of keratinocyte, fibroblast and other cells of interest with specific genetic manipulations using state of the art gene and cellular modification techniques. 2) Establish an Animal Model and Tissue Engineering Core to provide access to and expertise on a range of whole skin models. 3) Leverage new and existing resources to establish a Tissue Procurement and Analysis Core, which will provide a high quality, CAP-approved tissue and serum bank for human tissue and blood and related pathological/histopathological analyses. 4) Develop an active enrichment program, including a pilot grants program, Translational and Innovation Research Support grants, seminar series, annual meetings and a mentored research program directed at increasing interest of students and medical students, especially underrepresented minorities, in skin research.

Public Health Relevance

Skin diseases cause significant morbidity, and therapies are limited by lack of knowledge regarding mechanisms of skin disease. Our major objective is to accelerate investigation of the skin and skin diseases, and the eventual discovery of novel therapies, by providing access to key technologies and resources that will increase efficiency and breadth of current research and enable new lines of investigation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Center Core Grants (P30)
Project #
1P30AR066527-01
Application #
8738944
Study Section
Special Emphasis Panel (ZAR1-KM (M1))
Program Officer
Tseng, Hung H
Project Start
2014-08-01
Project End
2016-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
1
Fiscal Year
2014
Total Cost
$628,665
Indirect Cost
$228,665
Name
Duke University
Department
Dermatology
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
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
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
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
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
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
Thakore, Pratiksha I; Black, Joshua B; Hilton, Isaac B et al. (2016) Editing the epigenome: technologies for programmable transcription and epigenetic modulation. Nat Methods 13:127-37
Black, Joshua B; Adler, Andrew F; Wang, Hong-Gang et al. (2016) Targeted Epigenetic Remodeling of Endogenous Loci by CRISPR/Cas9-Based Transcriptional Activators Directly Converts Fibroblasts to Neuronal Cells. Cell Stem Cell 19:406-14

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