Pierre A. Coulombe, PhD
- Biochemistry and Molecular Biology (Primary)
- School of Medicine (Joint)
615 N. Wolfe Street
Baltimore, Maryland 21205
PhD, University of Montreal, 1987
Topic: Structural and signaling roles of keratin cytoskeletal assemblies; Epithelial differentiation and homeostasis in health and disease.
Our laboratory studies the biology of complex epithelia, in health and in disease, from the perspective of large family of conserved genes encoding keratin cytoskeletal proteins. These proteins polymerize to form 10-nm wide “intermediate” filaments which, in vivo, are organized in intricate cytoplasmic networks anchored at the surface of the nucleus and at cell-cell and cell-matrix adhesion complexes.
A major role of keratin filaments is to endow epithelial cells and tissues with the ability to withstand mechanical stress. Mutations affecting keratin sequences underlie several inherited blistering diseases in which epithelial cells are fragile and rupture readily upon exposure to stress. We are studying the biochemical, biophysical, and structural determinants of this important function, and pursuing novel approaches to treat such diseases.
A newly defined role for keratins is to bind and modulate the activity of a variety of signaling effectors. In skin, we found that keratins impact the survival, growth, and immune function of keratinocytes, and that these contributions are physiologically important during wound repair, in the lifelong growth cycle of hair follicles, and in the context of chronic diseases such as cancer.
Honors and Awards
2013: Inaugural Mary Schwartz Lecture in Skin Biology, University of Dundee, UK
2013: Irwin M. Freedberg Memorial Lecture, Gordon Research Conference on Epithelial Differentiation
2009: Elected Fellow, Section of Biological Sciences, Amer. Assoc. Adv. Sciences
2008: E. V. McCollum Endowed Professorship, Bloomberg School of Public Health
2008: William F. Montagna lecturer, Society for Investigative Dermatology
2008: “Milestone Discovery” for the cytoskeleton, Nature Publishing Group
2000: Teacher of the Year, J.H.U. Graduate Student Association
1995-97: Junior Faculty Research Award - American Cancer Society
1994-95: James A. Shannon Director’s Award - National Institutes of Health
1992: Thomas B. Fitzpatrick Research Award in Dermatology
1989-92: Centennial Fellowship Award - Medical Research Council of Canada
- skin, epidermis, hair follicle and keratinocyte
- keratin, intermediate filament, cytoskeleton, and genodermatose
- tissue repair, cancer, inflammation, immunity, and gene expression
- Assays involving purified protein, cultured cells, and transgenic mouse models
Representative publications from the recent past are given here:
Lessard JC, Pina-Paz S, Rotty JD, Hickerson RP, Kaspar RL, Balmain A, Coulombe PA (2013). Keratin 16 regulates innate immunity in response to epidermal barrier breach. Proc Natl Acad Sci (USA) 110(48):19537-42.
Lee CH, Kim MS, Leahy DJ, Coulombe PA (2012). Structural basis for heterodimerization and cytoplasmic organization of keratin intermediate filaments. Nat. Struct. Mol. Biol. 19(7):707-15.
Rotty J, Coulombe PA (2012). A wound-induced keratin regulates Src activity during keratinocyte migration and tissue repair. J. Cell Biol. 197(3):381-9.
Pan X, Hobbs R, Coulombe PA (2012). The expanding significance of keratin intermediate filaments in normal and diseased epithelia. Curr. Opin. Cell Biol. 25(1): 47-56.
DePianto D, Kerns M, Dlugosz AA, Coulombe PA (2010). Keratin 17 promotes epithelial proliferation and tumor growth by polarizing the immune response in skin. Nat. Genet. 42: 910-4.