Peter J. Koch, Ph.D.

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Associate Professor of Dermatology
Charles C. Gates Regenerative Medicine and Stem Cell Biology Program
University of Colorado Denver (UCD)
Phone: 303 724 0051
Fax: 303 724 3051
E-Mail: Peter.Koch@uchsc.edu

 

 

 

Program and Departmental Associations:
Graduate Program in Cell Biology, Stem Cells and Development (CSD)
Biomedical Science Program of the UCD Graduate School
Dermatology Department
Medical Scientist Training Program (M.D./Ph.D.) of the UCD Graduate School
 
Cancer Cell Biology Program, UCD Cancer Center
 
Other Professional Activities:
Director, Transgenic and Gene Targeting Core; UCD Medical School
Education:
Ph.D. in Biology, University of Heidelberg, Germany, 1992
Postdoctoral Training:
German Cancer Research Center, Heidelberg, Germany, 1992-1994
National Institutes of Health, Bethesda, MD, 1994-1995
University of Pennsylvania, Philadelphia, PA, 1995-1998
Previous Faculty Appointments:
Departments of Dermatology and Molecular & Cellular Biology, Baylor College of Medicine, Houston, Texas
Research Interests:
Cell Adhesion Proteins, Cytoskeleton, Epithelial Cell Biology, Epidermal Stem Cells, Mouse Embryonic Development, Skin and Skin Appendage Development and Diseases, Blistering Skin Diseases, Desmosomes, Cancer

Current Laboratory Members:

Jiangli Chen, D.V.M., Ph.D.
Jiangli.Chen@uchsc.edu

Etienne Tokonzaba, Ph.D.
Etienne.Tokonzaba@uchsc.edu

Ling Wang, M.D.
Ling.Wang@uchsc.edu
(Transgenic and Gene Targeting Core, UCD)

Charlene O'Shea, B.S.
Charlene.Oshea@uchsc.edu

Previous Laboratory Members:

  • Xing Cheng, M.D. Ph.D.
  • Jin Han, Ph.D.
  • Zhining Den, M.D.
  • Maria Merched-Sauvage, M.S.
  • Marvin Coughenour, M.S.

Job Opportunities:

We are currently looking for talented and highly motivated graduate students and postdoctoral fellows that are interested in studying the function of cell adhesion systems in the development and maintenance of the skin and other epithelial organs using genetically engineered mice and cell culture systems. Candidates should contact Peter.Koch@uchsc.edu for further information.

Ongoing Research Projects:

Layman Version:

What we do:

Our laboratory is interested in the role of cell adhesion molecules in the development and maintenance of the skin. Furthermore, we are trying to understand how defects in cell adhesion molecules lead to skin disorders, such as blistering skin diseases, hair disorders and skin cancer.

The skin:

Keratinocytes are cells that form the epidermis, the uppermost part of the skin. All epidermal keratinocytes are derived from a group of cells that are located at the bottom of the epidermis and certain parts of hair follicles, the so called epidermal stem cells. These cells produce daughter cells that slowly move from the bottom of the epidermis to the skin surface where they are sloughed off into the environment. During this move, the cells slowly change their shape and their function (a process termed differentiation) thus producing the different cell layers of the epidermis.

The constant production of new epidermal cells and the loss of cells on the body surface lead to a turn over of the entire skin every 3-4 weeks. Only stem cells remain in the skin for our entire life. Inherited skin disorders and skin cancer are caused by defects in skin stem cells. In order to understand and eventually treat these diseases, we have to learn how stem cells and their daughter cells function in normal development and in diseases.

Scientific Version:

Desmosomes are multi-protein complexes which anchor the intermediate filament cytoskeleton at the plasma membrane of epithelial cells (see Figures below). 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 been shown that abnormal desmosome function can lead to lethal heart diseases (arrhythmogenic right ventricular dysplasia/cardiomyopathy).

Figure 1. (A) Human cultured epithelial cells (colon carcinoma cell line CaCo-2) were stained with antibodies against the intermediate filament (IF) protein cytokeratin 18 (open arrow) and the desmosomal plaque protein desmoplakin (white arrows). Desmosomes are aligned along the boundaries of the cells (white arrows) as small dots. Cytokeratin filaments pass through the cytoplasm and terminate in desmosomes at the plasma membrane. (B) Electron micrograph of desmosomes formed between mouse keratinocytes. In the apparent intercellular space between the cells (termed desmoglea) a narrow “midline” is visible (black arrow). The plasma membranes of the two cells that form a desmosome are marked with white arrows. Note the electron dense plaques on the cytoplasmic surfaces of the plasma membranes that connect the desmosome to the cytokeratin (CKs) intermediate filaments. (From “Desmosomes in Development and Diseases” by Schmidt and Koch, in press)

Figure 2. Simplified model of the desmosomal adhesion complex. Heterophilic interactions between the NH2-terminal extracellular domains of the desmosomal cadherins [desmocollins (Dsc; orange), desmogleins (Dsg; yellow)] are thought to establish cell-cell adhesion. The transmembrane proteins are anchored to the intermediate filament (IF) cytoskeleton (purple) via a complex of the plaque proteins plakophilin (Pkp; blue), plakoglobin (Pg; red) and desmoplakin dimers (Dp; green). Note that the “outer” and “inner” plaque consist of different proteins. The plasma membrane of adjacent cells is indicated (PM). (Modified from “Desmosomes – Just Cell Adhesion or Is There More?” by Schmidt and Koch, 2007; Cell Adhesion & Migration 1:28-32)

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 this 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 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 Peer-Reviewed 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.

Link to Other Publications