James K. Wahl, Ph.D.
Title: Associate Professor
NCCS Graduate and Director Live Cell Microscopy Core
Department of Oral Biology
UNMC College of Dentistry
40th and Holdrege
Lincoln, NE 68583-0740
Telephone: (402) 472-1324
Fax: (402) 472-2551
- B.S. (Biology), The University of Toledo, Toledo, Ohio
- Ph.D., The University of Toledo, Toledo, Ohio
- Course Instructor, Biochemistry (OB 545)
- Course Instructor, Advanced Oral Biology (OBIO 855)
- Cellular junctions are altered during metastasis allowing individual tumor cells to release from the primary tumor, migrate to secondary sites and re-establish cell-cell contacts. Desmosomes are prominent cell-cell junctions in stratified squamous epithelial tissues that confer upon cells the ability to function coordinately as a tissue and to withstand mechanical stress. In stratified squamous epithelia, such as oral epithelia, the molecular components of the desmosomes are expressed in a differentiation-dependent manner. As a result, desmosomes between cells attached to the basement membranes are compositionally different from desmosomes between cells in the upper, more differentiated layers. It is likely that desmosomes comprised of different molecular components perform diverse functions and lead to altered adhesive characteristics. Therefore, it is important to understand the functional characteristics of compositionally different junctions.
- Although desmosomal protein expression is generally reduced in squamous cell carcinomas, the contribution of these proteins to tumorigenesis is largely unknown. My long-term goals are to understand the role desmosomes play in maintaining the normal phenotype of squamous epithelial tissues and to determine if their alteration during tumorigenesis influences cell motility, metastasis and signaling.
- Our central hypothesis is that changes in desmosomal composition result in differential adhesion and/or altered cell-cell signaling. This hypothesis is based on our previous findings that different junctional proteins confer distinct adhesive characteristics on epithelial cells, and that formation of various cell junctions initiates cell adhesion-dependent signaling pathways.
- Source: National Institutes of Health Title: Role of plakophilin-1 in HNSCC Role: Principal Investigator Period of Support: 7/1/06-6/30/10The goal of this grant is to investigate the nuclear function of the desmosomal plaque protein plakophilin-1 and to examine the role of plakophilin-1 in the progression of head and neck squamous cell carcinoma.
- Keim, S.A., Johnson, K.R., Wheelock, M.J. and Wahl III, J.K. Generation and characterization of monoclonal antibodies against the proregion of human desmoglein-2. Hybridoma27(4):249-58, 2008 Aug.
- Bass-Zubek, A.E., Hobbs, R.P., Amargo, E.V., Garcia, N.J., Hsieh, S.N., Chen, X., Wahl III, J.K., Denning, M.F. and Green, K.J. Plakophilin 2: A critical scaffold for PKC alpha that regulates intercellular junction assembly. J Cell Biol181(4):605-13, 2008 May 19 (Epub 2008 May 12).
- Sobolik-Delmaire, T., Katafiasz, D., Keim, S.A., Mahoney, M.G. and Wahl 3rd, J.K. Decreased plakophilin-1 expression promotes increased motility in head and neck squamous cell carcinoma cells. Cell Commun Adhes14:99-109, 2007.
- Theisen, C.S., Wahl 3rd, J.K., Johnson, K.R. and Wheelock, M.J. NHERF links the N-cadherin/catenin complex to the PDGF receptor to modulate the actin cytoskeleton and regulate cell motility. Mol Biol Cell18(4):1220-32, Apr 2007.
- Wahl, J.K. Desmogleins and desmocollins as adhesive molecules. J Invest Dermatol127:E10 , 2007. (Invited Review)
- Mahoney, M.G., Hu, Y., Brennan, D., Bazzi, H., Christiano, A.M. and Wahl 3rd, J.K. Delineation of diversified desmoglein distribution in stratified squamous epithelia: implications in diseases. Exp Dermatol15:101-9, 2006.
- Bazzi, H., Getz, A., Mahoney, M.G., Ishida-Yamamoto, A., Langbein, L., Wahl 3rd, J.K. and Christiano, A.M. Desmoglein 4 is expressed in highly differentiated keratinocytes and trichocytes in human epidermis and hair follicle. Differentiation74:129-40, 2006.
- Sobolik-Delmaire, T., Katafiasz, D. and Wahl 3rd, J.K. Carboxyl terminus of plakophilin-1 recruits it to plasma membrane, whereas amino terminus recruits desmoplakin and promotes desmosome assembly. J Biol Chem281:16962-70, 2006.
- Maeda, M., Johnson, E., Mandal, S.H., Lawson, K.R., Keim, S.A., Svoboda, R.A., Caplan, S., Wahl, 3rd, J.K., Wheelock, M.J. and Johnson, K.R. Expression of inappropriate cadherins by epithelial tumor cells promotes endocytosis and degradation of E-cadherin via competition for p120(ctn). Oncogene25:4595-604, 2006.
- Kim, Y.J., Sauer, C., Testa, K., Wahl, J.K., Svoboda, R.A., Johnson, K.R., Wheelock, M.J. and Knudsen, K.A. Modulating the strength of cadherin adhesion: evidence for a novel adhesion complex. J Cell Sci1;118 (Pt 17):3883-94, 2005 Sept.
- Wahl, J.K. A role for plakophilin-1 in the initiation of desmosome assembly. J Cellular Biochem1;96(2):390-403, 2005 Oct.
- Brennan, D., Hu, Y., Kljuic, A., Choi, Y., Joubeh, S., Bashkin, M., Wahl, J.K., Fertalal, A., Pulkkinen, L., Uitto, J., Chistiano, A.M., Panteleyev, A. and Mahoney, M.G. Differential structural properties and expression patterns suggest functional significance for multiple mouse desmoglein 1 isoforms. Differentiation72:434-449, 2004.
- Wahl, J.K., Kim, Y, Cullen, J., Johnson, K.R. and Wheelock, M.J. N-cadherin/catenin complexes form prior to cleavage of the proregion and transport to the plasma membrane. J Biol Chem278:17269-76, 2003.
- Wahl, J.K. Generation of monoclonal antibodies specific for desmoglein family members. Hybridoma and Hybridomics21:37-44, 2002.
- Jackson, D., Dhar, K., Wahl, J.K., Wold, M. and Borgstahl, G.E. Analysis of the human replication protein A:Rad52 complex: evidence for crosstalk between RPA32, PRA70, Rad52 and DNA. J Mol Biol321:133-148, 2002.
- Bercher, M., Wahl, J.K., Vogel, B., Lu, C., Hedgecock, E., Hall, D. and Plenefisch, J. mua-3 a gene required for mechanical tissue integrity in Caenorhabditis elegans, encodes a novel transmembrane protein of epithelial attachment complexes. J Cell Biol154: 415-426, 2001.
- Wahl, J.K., Nieset, J.E., Sacco-Bubulya, P.A., Sadler, T.M., Johnson K.R. and Wheelock M.J. The amino- and carboxyl-terminal tails of beta-catenin reduce its affinity for desmoglein 2. J Cell Sci113:1737-45, 2000.
- Hakuno, M., Shimizu, H., Akiyama, M., Amagai, M., Wahl, J.K., Wheelock, M.J. and Nishikawa, T. Dissociation of intra- and extracellular domains of desmosomal cadherins and E-cadherin in Hailey-hailey disease and Darier's disease. Br J Dermatol142:702-11, 2000.
- Proby, C.M., Ota, T., Suzuki, H., Koyasu, S., Gamou, S., Shimizu, N., Wahl, J.K., Wheelock, M.J., Nishikawa, T. and Amagai, M. Development of chimeric molecules for recognition and targeting of antigen-specific B cells in pemphigus vulgaris. Br J Dermatol142:321-30, 2000.
- Wu, H., Wang, Z.H., Yan, A., Lyle, S., Fakharzadeh, S., Wahl, J.K., Wheelock M.J., Ishikawa, H., Uitto, J., Amagai, M. and Stanley, J.R. Protection against pemphigus foliaceus by desmoglein 3 in neonates. New Engl J Med 343:31-35, 2000.
- Department of Adult Restorative Dentistry
Department of Dental Hygiene
- Department of Growth & Development
- Department of Oral Biology
- Department of Surgical Specialties