Walter M. Holleran, PharmD
Research Chemist, SFVAMC
Adjunct Professor, Dermatology and Pharmaceutical Chemistry, UCSF
Email: walter.holleran@ucsf.edu
Improving the Skin Barrier
The protective barrier of human skin is embedded in a lipid matrix consisting of cholesterol, fatty acids, and a unique class of nitrogen-containing lipids called ceramides. Many skin diseases that affect both veterans and the general population have alterations in the normal pattern of cells and/or lipid layers. Dr. Holleran has defined many of the biochemical processes that allow for normal skin barrier function to develop and persist. His current work, in collaboration with other SFVAMC researchers, explores mechanisms that protect the critical outer skin layers against oxidative stress insults, such as those due to ultraviolet light exposure. After these insults, large quantities of ceramide lipids are produced, which in turn threatens skin cells with premature cell death, called apoptosis. Dr. Holleran's team has defined two enzymatic pathways that protect the outer skin layers from oxidative stress. In addition, Dr. Holleran's recent collaborative efforts have revealed a critical role for a gene family, called the ‘grainyhead-like' Grhl genes, in the formation and healing of the normal protective skin barrier. These mechanisms could be exploited to develop novel therapies for a number of skin disorders, including atopic dermatitis, which affects approximately 10 percent of the veteran population.
Uchida Y, Holleran WM. 2008. Omega-O-acylceramide, a lipid essential for mammalian survival. J Dermatol Sci 51(2):77-87.
Hatano Y, Man MQ, Uchida Y, Crumrine D, Scharschmidt TC, Kim EG, Mauro TM, Feingold KR, Elias PM, Holleran WM. 2009. Maintenance of an acidic stratum corneum prevents emergence of murine atopic dermatitis. J Invest Dermatol 129(7):1824-35.
