Barbara E. Hull, Ph.D.
Ph.D., 1976, University of Colorado
The skin protects the body against infection, excess water loss, temperature fluctuations, toxic chemicals and solar radiation. The major classes of epidermal cells (keratinocytes, melanocytes, Langerhans cells, and gd T-cells) that comprise the outer or epidermal layer of skin form a protective barrier for the body. The underlying dermis, populated by fibroblasts, provides nutritional support and mechanical protection for the epidermis. The bilayered skin equivalent, formed by layering keratinocytes over a collagen matrix populated with fibroblasts, serves as a useful model system for studying the cellular mechanisms of wound healing and graft rejection. We are currently studying the mechanism whereby fibroblasts in a dermal equivalent align to an external electric field. During the crucial first two hours after addition of the fibroblasts to the collagen matrix, the cells initiate alignment to the exogenous electrical field; this alignment depends on exogenous calcium and dynamic populations of microtubules and microflaments.
We are also investigating the cellular mechanisms of defense against viral pathogens such as Herpes Simplex Virus-1 (HSV-1). The mouth is lined by a specialized epithelium, the oral or buccal mucosa; these cells differ from the epidermal keratinocytes by retaining nuclei. The primary infection with HSV-1 typically involves the mouth; at the site of infection, the viral antigens are presented by Langerhans cells and macrophages to CD4+ Th1 lymphocytes. These lymphocytes trigger clearance of the virus by CD8+ T-cells and Natural Killer (NK) cells. The interactions between the epidermal keratinocytes and the antigen presenting cells are poorly understood, but play an essential role in triggering the immune response clearing the virus from the infected epidermal cells. The initial infection as well as the recurrent oral lesions depends on replication of the HSV-1 in the keratinocytes of the mouth. The virus then enters the trigenimal ganglia and the brain, where it establishes latency. Our current goal is to study the efficacy of a DNA vaccine in protecting against the initial viral infection, establishment of latency, and the reactivation of the virus by stressors.
Rogers, J.V., N.J. Bigley, H.C. Chiou , and B.E. Hull. 2000. Targeted delivery of DNA encoding herpes simplex virus type-1 glycoprotein D enhances the cellular response to primary viral challenge (revised manuscript submitted 7/12/00 to Archives of Dermatologic Research).
Taschenberger, L.M, J.V. Rogers, and B.E. Hull. 2000. A graft chamber delays rejection of murine allogeneic skin equivalents. Archives of Dermatologic Research 292: 46-49.
Rogers, J.V., B.E. Hull, P.S. Fink , H.C. Chiou , and N.J. Bigley. 2000. Murine response to DNA encoding herpes simplex virus type-1 glycoprotein D targeted to the liver. Vaccine18:1522-1530.
Hendrix, S.W., J.V. Rogers, and B. E. Hull. 1998. Basal keratinocytes in a human skin equivalent respond to ultraviolet irradiation. Archives of Investigative Dermatology 290:420-424.
Graeter, L.J. and B.E. Hull. 1996. Characterization of label retaining cells in the epidermis of a human skin equivalent. Cell Proliferation 29: 679-688.
Harriger, M.D. and B.E. Hull. 1994. Characterization of ultraviolet light-induced damage to keratinocytes in a skin equivalent in vitro. Archives of Investigative Dermatology 286:319-324.
Hull, B.E. and C.F. Elking. 1994. Rejection of rat skin-equivalent grafts constructed with allogeneic epidermal cells depleted of Langerhans cells. Journal of Investigative Dermatology 102:581.