Research in the laboratory focuses on the regulation of cell differentiation and tissue homeostasis in complex epithelia such as skin, which we study from the unique perspective of keratin intermediate filament genes and proteins. A major role of keratin filaments is to endow epithelial cells and tissues with the ability to withstand mechanical and other forms of stresses. Genetic mutations that affect the primary structure of individual keratin proteins compromise this role and underlie several inherited blistering diseases in which epithelial cells are fragile and prone to rupture upon exposure to physical stress. We study the biochemical and structural determinants of this vital role, and are pursuing novel approaches to treat keratin-based genetic diseases.

A newly defined role for keratins is to modulate the activity of regulators and signaling effectors in epithelial cells, with a significant impact on homeostasis in complex epithelia. Thus we discovered that keratins may impact the survival, growth, and architecture of keratinocytes in skin epithelia, and that such contributions can be crucially important during wound repair, in the lifelong growth cycle of hair follicles, and in the context of genodermatoses, cancer, and related diseases. The laboratory also discovered a role for keratins in the regulation of protein synthesis and epithelial cell growth, and the regulation of inflammation and innate and acquired immunity, in skin tissue. Recently, we discovered that keratin proteins occur inside the cell nucleus, where they contribute to regulating the expression of genes involved in inflammation and immune responses. Keratin proteins also participate in the regulation of the redox balance in skin keratinocytes. Here again, the laboratory is interested in assessing whether targeting keratin expression is of interest when developing novel therapies for chronic skin disorders and cancer.

Research

Epithelial Homeostasis in Health and Disease

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