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Peter J. Koch, Ph.D.

Professor


Program and Departmental Associations:

Department of Dermatology
Department of Cell and Developmental Biology
Graduate Program in Cell Biology, Stem Cells and Development (CSD)
Biomedical Science Program of the UC AMC Graduate School
Medical Scientist Training Program (M.D./Ph.D.) of the UC AMC Graduate School

Koch Lab 

Director: Bioengineering Core, UC 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, Epidermal Stem Cells, Stem Cells, Induced pluripotent stem (iPS) Cells, Tissue Engineering

 

Koch Lab

Jiangli Chen
Abhilasha Jain

 


Saiphone Webb
Jason Dinella
      Previous Lab Members
    • Xing Cheng, M.D. Ph.D.
    • Jin Han, Ph.D.
    • Zhining Den, M.D.
    • Maria Merched-Sauvage, M.S.
    • Marvin Coughenour, M.S.
    • Ling Wang, M.D.
    • Etienne Tokonzaba, Ph.D.
    • Radhika Ganeshan, Ph.D.
    • Nitya Maddodi, Ph.D.

 

       

Scientific Interests:

Currently, the main focus of my laboratory is the use of stem cell technology to elucidate disease mechanisms underlying a group of diseases termed ectodermal dysplasias (ED; www.nfed.org). Further, our long term goal is to provide proof-of-principle that stem cell-based therapies can be used to treat epithelial lesions in these diseases. In collaboration with Dr. Maranke Koster , we developed a project to analyze the molecular pathology underlying ectodermal dysplasias (ED) using iPSC-based disease modeling (see Koster et al., 2014; Koch et al., 2014 and Dinella et al., 2014). EDs are a group of inherited disorders with defects in several organ systems, including the skin and the eye. These diseases are caused by mutations in the transcription factor TP63. Our funded project focuses on the pathophysiology of ED in the skin.

We are now extending our research into the role of TP63 in the limbal stem cell (LSC) compartment of the eye, which is a natural extension of our long term goal to understand the role of this protein in epithelial stem cells. Our experimental design utilizes animal models to assess in vivo effects of TP63 in several interconnected tissue and organ systems of the eye (e.g. limbus, cornea). These experiments are complemented with studies utilizing human iPSC-derived limbal epithelial cells from ED patients and primary mouse limbal epithelial cells to assess the cell autonomous role of TP63 in LSC.

Research interests unrelated to stem cells: I have a long standing interest in the role of cell adhesion proteins in the skin, especially with respect to their role in normal development, fragility disorders and skin cancer. We have recently demonstrated that loss of a desmosomal adhesion protein (DSC3) leads to skin fragility in mice. Work by others has now shown that mutations in DSC3 gene occur in humans causing a blistering skin disorder, i.e. we were the first to point to a new disease mechanism relevant to skin fragility syndromes. Further, we have demonstrated that loss of certain desmosomal protein expression is a crucial step in skin tumor progression, specifically at the transition from benign papillomas to malignant squamous cell carcinomas. Further, we identified epidermal signaling cascades that regulate desmosomal gene expression during skin appendage development. These studies established for the first time a link between signaling pathways essential for the formation of skin appendages (EDAR/NFkB and TCF/Lef-1) and cell adhesion. This observation led to our hypothesis that morphogenetic movements of keratinocytes during skin appendage formation are controlled by these pathways, at least in part by modulating desmosomal cell-cell contacts.

Click here for Bibliography


Koch Lab: Fig. 1 


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)

Koch Lab: Fig. 2


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)


 

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.

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