Peter J. Koch Associate Professor Department of Dermatology Ph.D., University of Heidelberg, Germany, 1992 UC D - Anschutz Medical Campus RC-1 North, Room P18-8133 Mail Stop 8320 12801 East 17th Ave Aurora, CO 80045 Phone: 303-724-0051 Fax: 303-724-3051 Email: Peter.Koch@ucdenver.edu

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Departmental Affiliations Dermatology Group Charlene O’Shea, B.S., PRA Members: Jiangli Chen, Ph.D., D.V.M., Instructor   Etienne Tokonzaba, Ph.D., Postdoctoral Fellow

Other Graduate Program Affiliations Biomedical Sciences Program (BSP) Medical Scientist Training Program (MSTP) Other Affiliations Charles C. Gates Regenerative Medicine and Stem Cell Biology (RMSCB) Program, UC D UCD Cancer Center Director: Transgenic and Gene Targeting Core

The Role of Desmosomal Cell Adhesion Proteins in Development and Diseases

Desmosomes are multi-protein complexes which anchor the intermediate filament cytoskeleton at the plasma membrane of epithelial cells. Desmosomes also function as cell adhesion structures (cell junctions) that connect neighboring cells. Consequently, impaired desmosome function can lead to tissue fragility disorders. The classic examples of desmosomal diseases are blistering skin disorders (e.g. pemphigus diseases). In recent years, it has also been shown that abnormal desmosome function can lead to lethal heart diseases (arrhythmogenic right ventricular dysplasia/cardiomyopathy).

Immunofluorescence microscopy using cultured epithelial cells that were stained with antibodies against a desmosomal protein (desmoplakin, yellow) and an intermediate filament protein (keratin 8, red). Nuclei are shown in blue. Note that desmosomes line up like “pearls on a string” along the plasma membrane of cells that are in direct contact. Desmosomes also anchor the intermediate filaments at the plasma membrane.

One major goal of our research is to elucidate the role of cell adhesion systems, in particular desmosomes, in the development and maintenance of skin and its appendages. Furthermore, we are interested in how mutations in desmosomal genes affect the susceptibility of epidermal stem cells to skin cancer formation. To address these question, we generate and analyze genetically engineered mouse lines (conventional and BAC transgenics, mice with inducible and tissue-specific transgene expression, conventional knockout mice, inducible and tissue-specific knockout and knockin mice). Further, we use a basic cell biological and biochemical approach to test the effects of mutations in desmosomal genes on cell behavior in vitro.

Selected Publications

Schmidt, A. and P. J. Koch. 2007. Desmosomes: Just Cell Adhesion or is there more? Cell Adhesion & Migration. 1:28-32.

Chen, J., X. Cheng, M. Merched-Sauvage, Dennis R. Roop, and P. J. Koch. 2007. Reply to: The ends of a conundrum? J. Cell Sci., 120:1147-1148

Chen, J., X. Cheng, M. Merched-Sauvage, Dennis R. Roop, and P. J.Koch. 2006. An unexpected role for keratin 10 end domains in susceptibility to skin cancer. J. Cell Sci. 119: 5067-5076

Den, Z., X.Cheng, M.Merched-Sauvage, and P.J.Koch. 2006. Desmocollin 3 is required for pre-implantation development of the mouse embryo. J. Cell Sci. 119:482-489.

Cheng, X., Z.Den, and P.J.Koch. 2005. Desmosomal cell adhesion in mammalian development. Eur. J. Cell Biol. 84:215-223.

Yang, T., D.Liang, P.J.Koch, D.Hohl, F.Kheradmand, and P.A.Overbeek. 2004. Epidermal detachment, desmosomal dissociation, and destabilization of corneodesmosin in Spink5-/- mice. Genes Dev. 18:2354-2358.

Koch, P.J. and D.R.Roop. 2004. The role of keratins in epidermal development and homeostasis-going beyond the obvious. J. Invest.Dermatol. 123:x-xi

Cheng, X., K.Mihindukulasuriya, Z.Den, A.P.Kowalczyk, C.C.Calkins, A.Ishiko, A.Shimizu, and P.J.Koch. 2004. Assessment of splice variant-specific functions of desmocollin 1 in the skin. Mol. Cell Biol. 24:154-163.

Cheng, X. and P.J.Koch. 2004. In vivo function of desmosomes. J. Dermatol. 31:171-187

Koch, P.J., P.A.de Viragh, E.Scharer, D.Bundman, M.A.Longley, J.Bickenbach, Y.Kawachi, Y.Suga, Z.Zhou, M.Huber, D.Hohl, T.Kartasova, M.Jarnik, A.C.Steven, and D.R.Roop. 2000. Lessons from loricrin-deficient mice. Compensatory mechanisms maintaining skin barrier function in the absence of a major cornified envelope protein. J Cell Biol. 151:389-400.

Koch, P.J., M.G.Mahoney, G.Cotsarelis, K.Rothenberger, R.M.Lavker, and J.R.Stanley. 1998. Desmoglein 3 anchors telogen hair in the follicle. J. Cell Sci. 111 ( Pt 17):2529-2537.

Koch, P.J., M.G.Mahoney, H.Ishikawa, L.Pulkkinen, J.Uitto, L.Shultz, G.F.Murphy, D.Whitaker-Menezes, and J.R.Stanley. 1997. Targeted disruption of the pemphigus vulgaris antigen (desmoglein 3) gene in mice causes loss of keratinocyte cell adhesion with a phenotype similar to pemphigus vulgaris. J. Cell Biol. 137:1091-1102.

Book Chapters

Schmidt, A., and Koch, P.J. Desmosomes in Development and Diseases. In Cell Junctions: Adhesion, Development and Disease, A. Kowalczyk and S. LaFlamme editors, Wiley-VCH, in press

Arin, M.J., Roop, D.R., Koch, P.J., and Koster, M. I. Biology of Keratinocytes. In Dermatology 2nd edition, J. Bolognia editor. Elsevier, in press

Koch, P.J., Z.Zhou, and D.R.Roop. 2004. Cornified Envelope and Corneocyte-Lipid Envelope. In Skin Barrier. P.M.Elias and K.R.Feingold, editors. Marcel Dekker, Inc., New York.

Koch, P.J. and D.R.Roop. 2002. Loricrin. In Wiley Encyclopedia of Molecular Medicine. John Wiley & Sons Inc., New York. 1956-1959.

Kartenbeck, J., P.J.Koch, and W.W.Franke. 1993. Desmoglein. In Guidebook to the Extracellular Matrix and Adhesion Proteins. T.Kreis and R.Vale, editors. Oxford University Press, Oxford, New York, Tokyo. 133-135.

Latest Publications in PubMed