Ph.D. in Biology, University of Heidelberg, Germany, 1992
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
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, Epidermal Stem Cells, Stem Cells, Induced pluripotent stem (iPS) Cells, Tissue Engineering
Ongoing Research Projects
What we do:
Our laboratory is interested in the role of cell adhesion molecules in the development and maintenance of the skin. Cell adhesion proteins are required to attach cells to each other or to the extracellular matrix (a mixture of proteins that surrounds cells). Further, our goal is to understand how inherited and acquired defects in cell adhesion molecules and certain transcription factors (p63) lead to skin and hair disorders.
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.
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
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, 2007)
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.
A new area of research in our laboratory is the role of
the transcription factor p63 in a group of inherited skin disorders, termed
ectodermal dysplasias (e.g. AEC; Ankyloblepharon Ectodermal Dysplasia and Clefting).
This work, done in collaboration with Maranke Koster, aims at elucidating the molecular
mechanisms underlying these severe childhood diseases which affect skin and
skin appendages. Using induced
pluripotent stem cell (iPSC) technology, the Koster and Koch laboratories are
establishing in vitro and in vivo models of skin diseases caused by p63
mutations. These tools will be invaluable for understanding the patho-mechanism
of ectodermal dysplasias and to develop therapeutic strategies for these severe
diseases. For more information regarding ectodermal dysplasias see Dr. Koster's webpage and visit www.nfed.org.
Selected Peer-Reviewed Publications:
- Ganeshan, R., J. Chen, and Peter J. Koch 2010. Mouse models for blistering skin disorders. Dermatology Research and Practice, Article ID 584353 (online format)
- Chen, J., Z. Den, and Peter J. Koch. 2008. Loss of desmocollin 3 in mice leads to epidermal blistering. Journal of Cell Science. 121:2844-2849
- 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.
- 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.