Diseases of the Integument Core

Directors: Jeffrey Laskin, PhD; Marion Gordon, Ph.D.

Members:
Suzie Chen, PhD
Allan Conney, PhD
Michael Gallo, PhD
Donald Gerecke, PhD
Ah-Ng (Tony) Kong, PhD
Debra Laskin, PhD
JK Lee, PhD
Jay Tischfield, PhD
Barry Weinberger, MD
Cliff Weisel, PhD
William Welsh, PhD
Lori A. White, PhD
CS Yang, PhD
Guofeng You, PhD
Helmut Zarbl, PhD
Junfeng (Jim) Zhang, PhD

Overview: 
The integument, which includes skin and cornea, is a major target organ of toxicity. The Core brings together investigators interested in elucidating pathophysiological mechanisms by which environmental exposures can cause, promote or prevent injury and disease in the skin and cornea.  Because development of injury and disease is a complex multi-stage process influenced by multiple genetic and environmental risk factors, understanding how these factors influence pathogenesis requires an interdisciplinary approach. The Core is organized into four working groups: 1) Mechanisms of Skin and Corneal Toxicity, 2) Xenobiotic Metabolism: DNA and Protein Damage, 3) Oxidative Stress and Inflammation, and 4) Epigenetic Responses and Signaling Processes.  Efforts within working groups range from basic science to integrative and clinical/translational studies. The Core includes members from other Disease Cores whose research interests overlap with the goals of the Diseases of the Integument Core. 

       
Overall Goals of the Diseases of the Integument Core

It is anticipated that these goals will lead to increased inter-Core and inter-disciplinary basic and translational research that contributes to research programs in the other Disease Cores. 
Short Term:

• Develop improved animal and in vitro models to assess the responses of the integument to toxicants.
• Define molecular and phenotypic responses associated with exposures of skin and cornea to xenobiotics.

Long Term:

• Define pathophysiological mechanisms that will lead to the discovery of biological response indicators of disease onset and progression, and translation to human studies.
• Develop countermeasures to minimize skin and eye injury for sulfur mustard and for other xenobiotics based on mechanistic discoveries for analogous agents.
• Development of interventions for use in clinical research.
• Core research focusing on the development of improved medical countermeasures to treat sulfur mustard poisoning in an effort to enhance medical response capabilities during an emergency will be disseminated by the COEC, targeting in particular medical and pharmacy students at UMDNJ and Rutgers University.

 
Use of Facility Cores by the Core

The Chemical Analysis Facility Core has provided metabolite identification, including eicosanoid metabolites induced by UVB light in primary cultures of mouse keratinocytes (J. Laskin), epigallocatechin metabolites in rodent and human studies (C.S. Yang), and quantitation of polycyclic aromatic hydrocarbon metabolites in human urine (C. Weisel, J. Zhang).  Using the Molecular Pathology unit of the Biological Response Indicators Facility Core (BRIC), D. Laskin and D. Gerecke identified cytokines and cytokine signaling pathways in tissues from toxicant-exposed animals, and A. Conney identified p53 expressing keratinocytes and apoptotic cells in rodent and human skin following exposure to ultraviolet light. Use of the analytical Cytometry/Image Analysis unit of the BRIC included cell cycle analysis and antigen expression following oxidative stress in epithelial cells (J. Laskin; M. Gordon), and for confocal microscopy (D. Laskin; D. Gerecke). Use of the BRIC for gene expression analysis continues to increase, including arrays from sulfur mustard-treated mouse skin to identify targets for drug intervention (D. Gerecke, W. Welsh), expression of antioxidant enzymes and phase II enzymes in mouse epidermal cells exposed to ultraviolet light (J. Laskin, A. Kong), and real-time PCR to quantify cytokine signaling pathways in neonates (B. Weinberger). H. Zarbl used the IHSFC and the CEF in U01 submission for planning human subject exposures and accessing and storing human tissue samples.