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, Ectodermal
Jiangli Chen, D.V.M., Ph.D.
Kenneth Barentsen, M.S.
Saiphone Webb, B.S.
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.
- Abhilasha Jain, M.S.
- Mellissa Tjandra
- Jason Dinella, Ph.D.
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
Click here for Bibliography
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)
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.