Professor and Associate Dean for Research
Chair, Department of Oral Biology
Room 1443, UNMC College of Dentistry
4000 East Campus Loop South
Lincoln, NE 68583-0740
- BS, Biology, The University of Toledo
- PhD, The University of Toledo
- Course Director, General Histology (ORBI 519)
- Course Instructor, Biochemistry (ORBI 545)
- Course Instructor, Research, Ethics, and Public Health (ORBI 620)
- 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 (R15AR065074)
Title: Mechanisms affecting desmosome dynamics
Role: Principal Investigator
Period of support: 6-1-2014 to 5-31-2017
The focus of this project is to investigate the role of 14-3-3 proteins in the assembly and maintenance of desmosomal adhesion and their influence on cell migration and invasion. Modulation of 14-3-3 protein association may provide of a mechanism of regulating cell-cell adhesion.
Source: National Institutes of Health
Title: Role of plakophilin-1 in HNSCC
Role: Principal Investigator
Period of Support: 7/1/2006-6/30/2010
The 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.
- Overmiller, A.M., Pierlussi, J.A., Wermuth, P.J., Sauma, S., Martinez-Outschoorn, U., Tuluc, M., Luginbuhl, A., Curry, J., Harshyne, L.A., Wahl, J.K. 3rd, South, A,P., and Mahoney, M.G. Desmoglein 2 modulates extracellular vesicle release from squamous cell carcinoma keratinocytes. The FASEB Journal 2017 Apr 24, doi: 10.1096/fj.201601138RR (Epub ahead of print).
- Roberts, B. J., R. A. Svoboda, A. M. Overmiller, J. D. Lewis, A. P. Kowalczyk, M. G. Mahoney, K. R. Johnson and J. K. Wahl, 3rd. 2016. Palmitoylation of desmoglein 2 is a regulator of assembly dynamics and protein turnover.J Biol Chem 291:24857-24865.
- Overmiller, A. M., K. P. McGuinn, B. J. Roberts, F. Cooper, D. M. Brennan-Crispi, T. Dequchi, S. Peltonen, J. K. Wahl, 3rd and M. G. Mahoney. 2016. C-Src/Cav1-dependant activation of the EGFR by Dsg2. Oncotarget 7(25):37536-37555.
- Luong, K. V., L. Wang, B. J. Roberts, J. K. Wahl, 3rd, and A. Peng. 2016. Cell fate determination in cisplatin resistance and chemosensitization. Oncotarget 26;7(17):23383-94.
- Mumaw, M.M., M. de la Fuente, A. Arachiche, J.K. Wahl, 3rd, and MT Nieman. 2015. Development and characterization of monoclonal antibodies against Protease Activated Receptor 4 (PAR4). Thromb Res 135:1165-1171.
- McAtee, C.O., A.R. Berkebile, C.G. Elowsky, T. Fangman, J.J. Barycki, J.K. Wahl, 3rd, O. Khalimonchuk, N. Naslavsky, S. Caplan, and M.A. Simpson. 2015. Hyaluronidase Hyal1 increases tumor cell proliferation and motility through accelerated vesicle trafficking. J Biol Chem 290:13144-13156.
- Katoch, P., S. Mitra, A. Ray, L. Kelsey, B.J. Roberts, J.K. Wahl, 3rd, K.R. Johnson, and P.P. Mehta. 2015. The carboxyl tail of connexin32 regulates gap junction assembly in human prostate and pancreatic cancer cells. J Biol Chem 290:4647-4662.
- Roberts, B.J., K.E. Johnson, K.P. McGuinn, J. Saowapa, R.A. Svoboda, M.G. Mahoney, K.R. Johnson and J.K. Wahl III. 2014. Palmitoylation of plakophilin is required for desmosome assembly. J. Cell Sci 127:3782-3793.
- Roberts, B.J., R. Reddy, and J.K. Wahl III. 2013. Stratifin (14-3-3 sigma) limits plakophilin-3 exchange with the desmosomal plaque. PLoS One. 8:e77012.
- Brennan, D., S. Peltonen, A. Dowling, W. Medhat, K.J. Green, J.K. Wahl III, F. Del Galdo, and M.G. Mahoney. 2012. A role for caveolin-1 in desmoglein binding and desmosome dynamics. Oncogene 31:1636-1648.
- Roberts, B.J., A. Pashaj, K.R. Johnson, and J.K. Wahl III. 2011. Desmosome dynamics in migrating epithelial cells requires the actin cytoskeleton. Exp Cell Res 317:2814-2822.
- Bharadwaj, A.G., N.P. Goodrich, C.O. McAtee, K. Haferbier, G.G. Oakley, J.K. Wahl III, and M.A. Simpson. 2011. Hyaluronan suppresses prostate tumor cell proliferation through diminished expression of N-cadherin and aberrant growth factor receptor signaling. Exp Cell Res 317:1214-1225.
- Katafiasz, D., L.M. Smith, and J.K. Wahl III. 2011. Slug (SNAI2) expression in oral SCC cells results in altered cell-cell adhesion and increased motility. Cell Adh Migr 5:315-322.
- Wang, L., L.A. Fisher, J.K. Wahl III, and A. Peng. 2011. Monoclonal antibodies against Xenopus greatwall kinase. Hybridoma (Larchmt) 30:469-474.
- Wang, H., Z.Y. Li, Y. Liu, J. Persson, I. Beyer, T. Moller, D. Koyuncu, M.R. Drescher, R. Strauss, X.B. Zhang, J.K. Wahl III, N. Urban, C. Drescher, A. Hemminki, P. Fender, and A. Lieber. 2011. Desmoglein 2 is a receptor for adenovirus serotypes 3, 7, 11 and 14. Nat Med 17:96-104.
- Sobolik-Delmaire, T., R. Reddy, A. Pashaj, B.J. Roberts, and J.K. Wahl III. 2010. Plakophilin-1 localizes to the nucleus and interacts with single-stranded DNA. J Invest Dermatol 130:2638-2646.
- Mahoney, M.G., S. Sadowski, D. Brennan, P. Pikander, P. Saukko, J.K. Wahl III, H. Aho, K. Heikinheimo, L. Bruckner-Tuderman, A. Fertala, J. Peltonen, J. Uitto, and S. Peltonen. 2010. Compound heterozygous desmoplakin mutations result in a phenotype with a combination of myocardial, skin, hair, and enamel abnormalities. J Invest Dermatol. 130:968-978.
- Narayana, N., J. Gist, T. Smith, D. Tylka, G. Trogdon, and J.K. Wahl III. 2010. Desmosomal component expression in normal, dysplastic, and oral squamous cell carcinoma. Dermatol Res Pract. 2010:649731.
- Hall, C., S. Li, H. Li, V. Creason, and J.K. Wahl III. 2009. Arrhythmogenic Right Ventricular Cardiomyopathy Plakophilin-2 Mutations Disrupt Desmosome Assembly and Stability. Cell Commun Adhes 1-13.
- 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. Hybridoma 27(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 Biol 181(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 Cell 18(4):1220-32, Apr 2007.
- Wahl, J.K. Desmogleins and desmocollins as adhesive molecules. J Invest Dermatol 127: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 Dermatol 15:101-9, 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. Differentiation 74:129-40, 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 Chem 281:16962-70, 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). Oncogene 25:4595-604, 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 Biochem 96(2):390-403, 2005.
- 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. Differentiation 72:434-449, 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 Chem 278:17269-76, 2003.
- Wahl, J.K. Generation of monoclonal antibodies specific for desmoglein family members. Hybridoma and Hybridomics 21:37-44, 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 Biol 321:133-148, 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 Biol 154: 415-426, 2001.
- Wahl, J.K., Nieset, J.E., Sacco-Bubulya, PA, 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 Sci 113:1737-45, 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 Dermatol 142:702-11, 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 Dermatol 142:321-30, 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.