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BCMBJHU SOM

Faculty & Research

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Pierre A. Coulombe

Department Affiliation Primary: Biochemistry & Molecular Biology, SPH
Secondary: Biological Chemistry
RankProfessor & Chairman, SPH Biochemistry and Molecular Biology
Phone Numbers410-955-3671
Lab: (410) 614-3734
Fax: (410) 955-2926
Emailcoulombe@jhsph.edu
School of Medicine Address615 N. Wolfe Street
W8041
Baltimore MD 21205
Link to Lab Homepage
Pierre A.   Coulombe

Research Topic: Structural and signaling roles of keratin cytoskeletal assemblies; Epithelial differentiation and homeostasis in health and disease; Cancer biology

Research in the Coulombe laboratory focuses on the regulation of cell differentiation and tissue homeostasis in complex epithelia such as skin, which it studies 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. We have found that keratins impact the survival, growth, and architecture of keratinocytes in skin epithelia, and that such contributions can be 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. More recently, we discovered that keratin proteins occur in the nucleus, whey they are bound the promoter of specific genes that they help regulate in the setting of chronic inflammatory skin disease and cancer. We are interested in assessing whether targeting keratin expression could be beneficial in such chronic diseases.

Publications:

Hobbs RP, DePianto D, Jacob JT, Han M, Zheng W, Wan F, Coulombe PA (2015). Keratin-dependent regulation of autoimmune regulator (Aire) and gene expression in skin tumor keratinocytes. Nature Genetics 47:933-8.
PubMed Reference 

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.
PubMed Reference

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.
PubMed Reference

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. Proceedings of the National Academy of Sciences USA 110: 19537-42.
PubMed Reference

Lee CH, Kim MS, Leahy DJ, Coulombe PA (2012).  Structural basis for hetero-dimerization and cytoplasmic organization of keratin intermediate filaments.  Nature Structural & Molecular Biology 19:707-15.
PubMed Reference

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.
PubMed Reference

 

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