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
Experiences & Accomplishments
Université de Montréal
Université du Québec à Montréal
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 & 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
Representative publications from the recent past are given here:
- Kerns ML, Lu R, Hakim J, Guo Y, Berroth A, Kaspar RL, Coulombe, PA (2016). Oxidative stress and dysfunctional Nrf2 precedes onset of pachyonychia congenita-associated palmoplantar keratoderma. Journal of Clinical Investigation 126(6):2356-66
- Hobbs RP, DePianto D, Jacob JT, Han MC, Chung BM, Batazzi AS, Poll BG, Guo Y, Han J, Ong S, Zheng W, Taube JM, Cihakova D, Wan F, Coulombe PA (2015). Keratin-dependent regulation of Aire and gene expression in skin tumor keratinocytes. Nature Genetics 47(8):933-8.
- Chung BM, Ilagan E, Arutyunov A, Yao N, Wills-Karp M, Coulombe PA (2015). Regulation of C-X-C chemokine gene expression by keratin 17 and hnRNP K in skin tumor keratinocytes. Journal of Cell Biology 208(5):613-27
- Feng X, Coulombe PA (2015). A role for disulfide bonding in keratin intermediate filament organization and dynamics in skin keratinocytes. Journal of Cell Biology 209:59-72.
- 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.