Mission statement and core values

The Coulombe laboratory strives to achieve scientific excellence at the highest level, make and report ground-breaking discoveries, and lead in various capacities in its efforts to study the development, differentiation and homeostasis of epithelial tissues in health and disease.

People, programs, and projects in place in the Coulombe laboratory are integrated so as to provide an outstanding training experience that fosters professional growth, innovation, independence, integrity, and rigor in an open, collaborative, congenial and hard working environment.

The core values of the laboratory include professionalism, innovation, productivity, rigor, integrity, and team work.

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Description of Research

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 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 rendered fragile and rupture readily 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 bind and modulate the activity of a variety of regulators and signaling effectors, with a significant impact on homeostasis in complex epithelia. We have discovered that keratins impact the survival, growth, and architecture of keratinocytes in skin epithelia, and that such contributions can be critically important during wound repair, in the lifelong growth cycle of hair follicles, and in the context of cancer, psoriasis, and related diseases. Also, the laboratory discovered a role for keratin proteins in the regulation of protein synthesis and epithelial cell growth, and in the regulation of inflammation and innate and acquired immunity, in skin tissue. Recently, we discovered that keratin proteins occur in the nucleus, where they are bound to promoters of and regulate the expression of specific genes involved in inflammation and immune responses, and 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.

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As an independent investigator appointed at the Johns Hopkins University since 1992, Dr. Coulombe has made several important contributions to our understanding of the structural support function provided by keratin filaments at a biochemical, biophysical, and structural levels, mainly through studies of K5-K14 filaments in basal layer keratinocytes and their defects in EBS.