OVERVIEW Epigenetic treatment of dermatologic disorders Walter H. Moos 1,2 | Douglas V. Faller 3,4 | Ioannis P. Glavas 5 | David N. Harpp 6 | Iphigenia Kanara 7 | Carl A. Pinkert 8 | Whitney R. Powers 9,10 | Konstantina Sampani 11,12 | Kosta Steliou 4,13 | Demetrios G. Vavvas 14,15 | Krishna Kodukula 2,13 | Robert J. Zamboni 6 1 Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, San Francisco, California 2 ShangPharma Innovation Inc., South San Francisco, California 3 Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 4 Cancer Research Center, Boston University School of Medicine, Boston, Massachusetts 5 Department of Ophthalmology, New York University School of Medicine, New York City, New York 6 Department of Chemistry, McGill University, Montreal, Quebec, Canada 7 Embassy of Greece in Moscow, Moscow, Russia 8 Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, Alabama 9 Department of Health Sciences, Boston University, Boston, Massachusetts 10 Department of Anatomy, Boston University School of Medicine, Boston, Massachusetts 11 Beetham Eye Institute, Joslin Diabetes Center, Boston, Massachusetts 12 Department of Medicine, Harvard Medical School, Boston, Massachusetts 13 PhenoMatriX, Inc., Natick, Massachusetts 14 Retina Service, Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts 15 Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts Correspondence Walter H. Moos, Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, UCSF Box 2280, 600 16th Street, Genentech Hall S512D, San Francisco, CA 94143. Email: walter.moos@ucsf.edu Krishna Kodukula, ShangPharma Innovation, Inc., 280 Utah Avenue, South San Francisco, CA 94080. Email: kkodukula@gmail.com Robert J. Zamboni, Department of Chemistry, McGill University, 801 Sherbrooke St. W., Montreal H3A 0B8, Quebec, Canada. Email: rjzambo@gmail.com Funding information MitoCure Foundation Abstract Healthy skin protects us against a multitude of insults, but injured or maladapted skin can lead to infection, inflammation, or worse. Fortunately, naturally occurring bioac- tive products, many commonly found in olive oil and other plant and vegetable extracts, have shown utility in treating skin and related diseases as well as condition- ing the skin to maintain its healthy function. Powerful agents targeting nuclear regula- tory pathways continue to hold promise as new or repurposed therapies for a wide variety of ills and skin conditions. Epigenetic approaches that activate Nrf2 to effect detoxification, redox balance, DNA repair, and mitochondrial function are notewor- thy. Some of the disease applications being actively investigated range from eczema and psoriasis to skin cancer and diabetes-related wound healing to name just a few. KEYWORDS diabetes, epigenetic, microbiome, mitochondrial dysfunction, skin diseases Abbreviations: ARE, antioxidant response element; CNC-bZIP, Cap'n'Collar basic-region leucine zipper; Nrf2, nuclear factor erythroid 2 (NFE2)-related factor 2; Nrf3, NFE2-related factor 3. Received: 8 May 2019 Revised: 15 June 2019 Accepted: 17 June 2019 DOI: 10.1002/ddr.21562 Drug Dev Res. 2019;1–12. wileyonlinelibrary.com/journal/ddr © 2019 Wiley Periodicals, Inc. 1