Page 11 - Gates-AnnualReport-2014

DEPARTMENT OF DERMATOLOGY
Generating skin stem cells (Courtesy of Anya Bilousova, PhD and Dennis Roop, PhD): Human induced Pluripotent Stem (iPS) cells (pink) can be differentiated into ectodermal cells (green) which subsequently differentiate into skin stem cells. Nuclei are stained blue. This approach is being used to develop novel therapeutic strategies for inherited skin blistering diseases where patient-specific iPS cells are generated, genetically corrected and differentiated into normal skin stem cells which are then returned to the same patient as an autograft.
Use of Stem Cells to Correct Skin Disease
The 2006 discovery in Japan by Shinya Yamanaka, MD, PhD, that one can induce normal adult skin cells to become pluripotent stem cells has provided staggering opportunities for correcting human genetic disease without using embryonic stem cells. Drs. Anya Bilousova, Igor Kogut and Roop are currently generating induced Pluripotent Stem Cells (iPSCs) from patients with inherited skin fragility syndromes using methods that do not require viral vectors, and determining whether genome editing techniques can be used to correct the genetic defect in these patient-specific iPSCs. The ultimate goal is to return keratinocytes derived from genetically corrected iPSCs to the same patient as an autograft. Drs. Bilousova and Kogut, both in the Department of Dermatology, are collaborating to devise optimal approaches for iPS generation to treat human diseases. The skin disease that is the best target for this approach is Epidermolysis Bullosa. This is a family of hereditary
skin diseases in which mutations in genes producing key structural proteins lead to extensive blisters of the skin. When the defective proteins produced in this disease cause full thickness blisters of the skin, they can lead to a life of intense suffering and early death. The second candidate disease for treatment is Epidermolytic Hyperkeratosis, a disease in which mutations
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