Testing Therapeutic Approaches for EHK Using a Preclinical Mouse Model (2006)

Dennis Roop, PhD
Jiang Chen, MD
University of Colorado Denver, Aurora, Colorado

 

Dr. Dennis Roop Dr. Jiang Chen

Drs. Roop and Chen have developed a genetically engineered mouse in which they have been able to generate areas of EHK (*EHK is currently referred to as EI) on the mouse's skin and paws. They will use this mouse model to test strategies to suppress or correct the expression of one of the mutant genes that causes EHK. This project is relevant to the mission of the Foundation and the interests of its members because, according to Dr. Roop, "Besides symptomatic care, no effective treatment is available for EHK. If the preclinical studies described above are successful, these strategies could be used to treat EHK patients.
 


UPDATE: SEPTEMBER 2007
We have developed a system that can efficiently deliver siRNA to defective primary epidermal keratinocytes isolated from our mouse model that mimics EHK. This delivery system was derived from a lentiviral vector. siRNAs are small therapeutic molecules that have been designed to specifically inhibit the expression of the mutant form of keratin 10 that is present in many EHK patients. We are currently testing whether the introduction of mutant keratin 10 specific siRNA into EHK keratinocytes will allow these cells to form a normal epidermis when they are grafted to form skin on a mouse. We have also begun to test a new delivery system that may allow siRNA to be delivered topically. This system utilizes nanotechnology, and we hope that this system will penetrate the thick hyperkeratotic skin that develops in areas prone to mechanical injury in EHK patients.
 


Dr. Dennis Roop is a professor of Molecular and Cellular Biology and Dermatology at Baylor College of Medicine in Houston, Texas. He is also the Director of the Center for Cutaneous Molecular Biology at Baylor and the leader of the Cancer Biology program, Cancer Center, Baylor College of Medicine. Dr. Roop received his education at Berea College, Berea, Kentucky, the University of Tennessee at Knoxville, and Baylor College of Medicine. Dr. Roop enjoys a distinguished career in cellular and molecular biology research and is the recipient of several notable research and lecture awards. Dr. Roop's work has contributed to the scientific community's knowledge of skin function, genetic skin disease, and skin cancer.

Dr. Jiang Chen is an instructor at Baylor College of Medicine. Dr. Chen received his education at Henan Medical University, the University of Heidelberg, and Baylor College of Medicine. Dr. Chen's work has focused on tumor development, wound healing, and genetic skin disease. Dr. Chen received a grant from FIRST in 2003 through the Dermatology Foundation Grant Program for his preliminary work on "Testing Gene Therapy Approaches for Epidermolytic Hyperkeratosis."



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