Kathleen J. Green, PhD Professor Pathology Intercellular adhesion in differentiation, cancer, skin and heart disease Curricula: Cancer Biology Cell Biology E-mail:   kgreen@northwestern.edu

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Cell adhesion plays a crucial role in embryogenesis, differentiation of adult tissues and wound healing. Our laboratory is studying the assembly, regulation and functions of intercellular junction molecules in desmosomes and adherens junctions that mediate cell-cell adhesion and attachment of the cytoskeleton to the cell surface. In particular, we are addressing how adhesion molecules coordinate their mechanical and signaling roles in normal tissues, as well as in cancer, skin and heart disease.

The transmembrane proteins of these junctions, known as cadherins, are engaged in bi-directional signaling. For instance, we have shown that cadherin function is modulated by growth factors such as EGF that drive cadherin internalization and degradation, thus contributing to loss of adhesion and the acquisition of motility that accompanies wound healing and tumor cell invasion.  On the other hand, we recently showed that a desmosomal cadherin called desmoglein 1, which is expressed only when epidermal cells make a commitment to stratify and undergo a program of differentiation, is capable of attenuating growth factor signaling in the epidermis. This function is required for facilitating the normal differentiation program of this epithelium, and importantly does not depend on desmoglein's adhesive capability. This work may lead to novel therapies for patients with striate palmar plantar keratoderma (SPPK) with desmoglein 1 haploinsufficiency.

Our lab is also investigating the structural and signaling roles of cadherin-associated proteins. We recently identified an associated armadillo protein called plakophilin 2 (PKP2) as a structural scaffold that coordinates PKC and rho GTPase signaling to regulate junction assembly locally while also affecting global intracellular signaling. This pathway may prove to be a key contributor to pathogenesis in the inherited disease ARVC (arrhythmogenic right ventricular cardiomyopathy), which leads to sudden death in patients harboring mutations in PKP2.

Current efforts are focused on defining the molecular mechanisms coupling cadherins and their associated proteins to these signaling pathways through a combination of proteomics and CytoTrap yeast two hybrid screens, cell biology (including living cell analyses using fluorescently tagged molecules), biochemistry, in vitro molecular genetic and transgenic mouse approaches.

Selected Publications:

Getsios, S., C.L. Simpson, S. Kojima, R. Harmon, L.J. Sheu, R.L. Dusek, M.L. Cornwell and K.J. Green. (2009). Desmoglein 1-dependent suppression of EGFR signaling promotes epidermal differentiation and morphogenesis.  J. Cell Biol. 185: 1243-58. 

Klessner, J., B. Desai, E.V. Amargo, S. Getsios and K.J. Green. (2009) EGFR and ADAM17 Cooperate to Regulate Shedding and Endocytic Trafficking of the Desmosomal Cadherin Desmoglein 2.  Mol. Biol. Cell.  20(1):328-37.

Bass Zubek, A.E., R. P. Hobbs, E.V. Amargo, N.J. Garcia, S. N. Hsieh, Chen, X., Wahl, J. K., M. Denning, and K.J. Green. (2008). Plakophilin 2: a critical scaffold for PKCa -that regulates intercellular junction assembly.  J. Cell Biol.  181: 605-613.

Godsel, L.M., R.P. Hobbs, and K.J. Green (2008). Intermediate filament assembly: strength through dynamics. Trends Cell Biol. 18: 28-37.

Abu-Yousif, A.O., K.A. Smith, S. Getsios, K.J. Green, and J.C. Pelling. (2008) Enhancement of UVB-induced apoptosis by apigenin in human keratinocytes and organotypic keratinocyte cultures. Cancer Res. 68: 3057-3065.

Green, K.J. and C.L. Simpson (2007). Desmosomes: New Perspectives on a Classic.  J. Invest. Derm. 127: 2499-2515.

Nava, P., M.G. Laukoetter, A.M. Hopkins, O. Laur, K.J. Green, C.A. Parkos and A. Nusrat (2007). Desmoglein-2: A novel regulator of apoptosis in the intestinal epithelium. Mol. Biol. Cell. 18: 4565-4578.

Dusek, R.L., L.M. Godsel, F. Chen, A. Strohecker, S. Getsios, R. Harmon, E. Müller, R. Caldelari, V.L. Cryns and K.J. Green (2007). Plakoglobin deficiency protects keratinocytes from apoptosis. J. Invest. Derm. 127(4):792-801.

Yang, Z, N.E. Bowles, S.E. Scherer, X. Sanchez, D.L. Kearney, S. Ge, V.V. Nadvoretskiy, G DeFreitas, B. Carabello, L.I. Brandon, L.M. Godsel, K.J. Green, H. Li, H. Calkins, F. Marcus, and J.A. Towbin (2006). Desmosomal dysfunction due to mutations in desmoplakin causes arrhythomogenic right ventricular dysplasia/cardiomyopathy. Circulation Res. 99(6):646-55.

View Publications by Kathy Green listed in the National Library of Medicine (PubMed).

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