Pierre A. Coulombe, PhD
Research in the Coulombe laboratory focuses on the regulation of cell differentiation and tissue homeostasis in complex epithelia such as skin, studied from the perspective of a large multigene family encoding keratin intermediate filament 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 keratin proteins compromise this role and underlie several inherited diseases in which epithelial cells are rendered fragile and/or unable to withstand stress. We have been studying the biochemical, biophysical, and structural determinants of this vital role with the goal of exploring novel approaches to treat keratin-based genetic diseases.
A newly defined role for keratin proteins is to bind and modulate the activity of a variety of signaling regulators and effectors. We have found that keratins impact the survival, growth, and architecture of keratinocytes in skin epithelia, and that such contributions are crucial during wound repair, in the lifelong developmental growth cycle of hair follicles, and in the context of cancer, psoriasis, and keratin mutation-based skin diseases. Our laboratory championed the discovery of several novel roles for keratin proteins, e.g., the regulation of protein synthesis and cell growth, of inflammation and both innate and acquired immunity, and of the balance between proliferation and differentiation via Hippo signaling, in skin tissue. More recently, the laboratory discovered that keratin proteins reside inside the nucleus, where they impact nuclear architecture, chromatin organization, gene expression, and DNA damage and repair, with direct relevance to tumor biology.