The epidermis, the outermost layer of skin, forms an essential barrier to the external environment. Keratinocytes, the dominant cells within epidermis, are firmly tethered to the underlying dermis via adhesion units and proteins that comprise epidermal basement membrane. In the skin, keratinocytes must adhere to the epidermal basement membrane and neighboring cells to cover the body surface and maintain effective barrier function. Acquired or inherited defects in adhesion molecules within keratinocytes are the basis of subepidermal blistering diseases that can produce significant morbidity and mortality. Such diseases can develop as a consequence of impairments in cell-cell or cell-matrix (i.e., epidermal basement membrane) adhesion.
Clinical and basic research activities in my laboratory are grounded on the hypothesis that defining the basis of autoimmune or inherited subepidermal blistering diseases will further understanding of epidermal and keratinocyte biology, lead to the identification of novel adhesion molecules, and provide great insights concerning the morphogenesis, growth, differentiation, wound healing, and cancer of epithelial tissues. The specific clinical research interests of my laboratory concern autoimmune blistering diseases and various forms of epidermolysis bullosa, a group of inherited blistering diseases. These research goals have direct relevance to the biology of skin as well as the etiology, diagnosis, and treatment of numerous dermatologic diseases.
Representative Research Aims
Specific Aim 1: To elucidate the pathophysiologic basis of autoimmune and inherited blistering diseases.
Specific Aim 2: To utilize transgenesis to create animal models of human blistering diseases.
Specific Aim 3: To identify ways to block unwanted immune responses to adhesion molecules in skin.
Specific Aim 4: To elucidate the relationship of selected autoimmune blistering diseases to underlying malignancies.
Specific Aim 5: To develop novel therapeutic interventions for patients with autoimmune blistering diseases.
Yancey, K.B., "The pathophysiology of autoimmune blistering diseases" J. Clin. Invest., 115:825-828, 2005
Rosenblum, M.D., Yancey, K.B., Olasz, E., Truitt, R.L., "CD200, a no danger signal for hair follicles" J. Dermatol. Sci., 41:165-174, 2006
Nishie, W., Sawamura, D., Goto, M., Ito, K., Shibaki, A., McMillian, J.R., Sakai, K., Nakamura, H., Olasz, E., Yancey, K.B., Akiyama, M., Shimizu H., "Humanization of autoantigen." Nature Medicine, 13:378-383, 2007
Olasz, E., Roh, J.Y., Yee, C., Arita, K., Akiyama, M., Shimizu, H., Vogel, J.C., Yancey, K.B., "Human bullous pemphigoid antigen 2 in transgenic skin elicits specific IgG in wild type mice." J. Invest. Dermatol., 127:2807-2817, 2007
SIGNIFICANT PUBLICATIONS
Domloge-Hultsch, N., Gammon, W.R., Briggaman, R.A., Gil, S.G., Carter, W.G., Yancey, K.B., "Epiligrin, the major human keratinocye intergrin ligand, is the target of disease in both an acquired autoimmune and an inherited subepidermal blistering skin disease." J. Clin. Invest., 90:1628-1633, 1992
Lazarova, Z., Yee, C., Darling, T., Briggaman, R.A., Yancey, K.B., "Passive transfer of anti-laminin 5 antibodies induces subepidermal blisters in neonatal mice." J. Clin. Invest., 98:1509-1518, 1996
Budinger, L., Borradori, L., Yee, C., Merk, H.F., Yancey, K.B., Hertl, M., "Autoreactive CD4+ T-cell responses to the extracellular domain of bullous pemphigoid antigen 2 (BPAG2) in patients with bullous pemphigoid." J. Clin. Invest., 102:2082-2089, 1998
Darling, T.N., Yee, C., Bauer, J.W., Hintner, H., Yancey, K.B., "Revertant mosaicism: partial correction of a germline mutation in COL17A1 by a frame restoring mutation." J. Clin. Invest., 103:1371-1377, 1999
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