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Spiro Getsios, PhD
Assistant Professor
Dermatology
Adjunct member, Department of Cell and Molecular Biology
Robert H. Lurie Comprehensive Cancer Center Tumor Invasion, Metastasis and Angiogenesis Program
Cell-cell adhesion and communication in development and disease
Curricula:
Molecular Biology and Genetics
Cell Biology
E-mail: s-getsios@northwestern.edu
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Defects in embryonic development, tissue homeostasis and unregulated growth in cancer occur when cells no longer sense or respond appropriately to their surroundings. Our laboratory aims to understand how cells receive and interpret information about their environment through adhesion and signaling receptors present on adjacent cell surfaces. Epithelial cells elaborate extensive cell-cell contact sites that render them particularly well-suited for physically interacting and directly exchanging information with their neighbors. We employ cell and biochemical approaches in primary epithelial cells isolated from human tissues to study the molecular composition, character and coordination of cell surface proteins that participate in adhesion-signaling networks during normal tissue formation and organization. Genetic reprogramming of primary skin cells is employed to test the importance of novel adhesion-signaling networks during epithelial morphogenesis in a three-dimensional raft model that mimics the human epidermis in vivo.
In the past, we have found that cell adhesion molecules of the cadherin family not only maintain epithelial tissue integrity by stabilizing cell-cell contacts but also orchestrate intracellular signaling pathways that control epidermal cell differentiation and morphogenesis. Our more recent work is focused on the role of the Eph receptor tyrosine kinase family in regulating epithelial tissue homeostasis. Eph receptors are engaged by ephrin ligands on adjacent cell surfaces and are thus intimately linked to the process of cell-cell adhesion. The activation of Eph receptors can in turn regulate signaling pathways that influence cell adhesion, proliferation and differentiation. Our goal is to therapeutically harness this adhesion-signaling network in order to restore epithelial tissue architecture during wound healing and in pathological conditions such as skin hyperplasia or cancer.
Selected Publications:
S Getsios*, CL Simpson*, R Harmon, S Kojima, LJ Sheu, RL Dusek, M Cornwell, S Crawford, and KJ Green (2009). Desmoglein 1-dependent suppression of EGFR signaling promotes epidermal differentiation and morphogenesis. J Cell Biol 185:1243-1258. *co-first authors.
JL Klessner, BV Desai, EV Amargo, S Getsios, and KJ Green (2009). EGFR and ADAMs cooperate to regulate shedding and endocytic trafficking of the desmosomal cadherin desmoglein 2. Mol Biol Cell 20:328-37.
J Yu, DG Ryan, S Getsios, M Oliveira-Fernandes, A Fatima, and RM Lavker (2008). MicroRNA-184 antagonizes microRNA-205 to maintain SHIP2 levels in epithelia. Proc Natl Acad Sci USA 105:19300-5.
A Abu-Yousif, KA Smith, S Getsios, RT Van Dross, KJ Green, and JC Pelling (2008).Enhancement of UVB-induced apoptosis by apigenin in human keratinocytes and organotypic keratinocyte cultures. Cancer Res 68:3057-3065.
S Getsios, E Amargo, RL Dusek, K Ishii, L Sheu, LM Godsel, and KJ Green (2004). Coordinated expression of desmoglein 1 and desmocollin 1 regulate intercellular adhesion. Differentiation 72:419-433.
S Getsios, AC Huen, and KJ Green (2004). Working out the strength and flexibility of desmosomal proteins. Nature Rev Mol Cell Biol 5:271-281.
