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Pierre A. Coulombe, Ph.D.

Photo of Dr. Pierre A. Coulombe, Ph.D.

Department Chair, Biochemistry and Molecular Biology

Joint Appointment in Biological Chemistry

Research Interests: Differentiation and homeostasis in (skin) epithelia; Structure, properties, and function of intermediate filaments; Translational approaches to treatment of genetic skin diseases; Role of keratin cytoskeleton in growth signaling pathways; Rregulation of innate and acquired immunity in skin; Novel determinants of tumor inception and growth. ...read more

Contact for Research Inquiries

Baltimore, MD 21205 map
Phone: 410-955-3671
Fax: 410-955-2926

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Background

Dr. Pierre Coulombe is a professor of biochemistry and molecular biology and dermatology at the Johns Hopkins University School of Medicine. He is a leading expert in the cytoskeleton and underlying causes of diseases affecting the skin.

Dr. Coulombe serves as the E.V. McCollum Professor and chair of the Johns Hopkins Bloomberg School of Public Health’s Department of Biochemistry and Molecular Biology. He is a member of the Johns Hopkins Kimmel Cancer Center.

He earned his Ph.D. from Université de Montréal and completed a postdoctoral fellowship at the University of Chicago.

His research focuses on the keratin filament cytoskeleton in epithelial cells with an emphasis on skin tissue. He is working to gain a better understanding of keratin genes at a mechanistic and molecular level. His laboratory discovered several novel functions for keratin proteins, including a role in regulating protein synthesis and epithelial cell growth during epithelial remodeling events. Dr. Coulombe’s research has led him to devise a therapeutic strategy for the treatment of epidermolysis bullosa simplex (EBS) and related disorders.

Dr. Coulombe has received numerous awards for both his teaching and research. In 2009, he was elected as a fellow for the American Association for the Advancement of Science. Coulombe has authored 111 publications and is the co-inventor of the patented use of Nrf2 inducers to treat epidermolysis bullosa simplex and related diseases.

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Titles

  • Department Chair, Biochemistry and Molecular Biology
  • E.V. McCollum Professor
  • Joint Appointment in Biological Chemistry
  • Joint Appointment in Dermatology
  • Joint Appointment in Oncology

Research & Publications

Research Summary

Dr. Coulombe’s research primarily focuses on the keratin filament cytoskeleton in epithelial cells with an emphasis on skin tissue. He is working to gain a better understanding of keratin genes at a mechanistic and molecular level.

The Coulombe laboratory discovered several novel functions for keratin proteins, including a role in regulating protein synthesis and epithelial cell growth during epithelial remodeling events. Keratin gene mutations are causative for a large number of dominantly inherited diseases, such as epidermolysis bullosa simplex (EBS).

Following his discovery of mutations in select keratin genes of EBS sufferers, which he made as a postdoctoral fellow at the University of Chicago, Dr. Coulombe has continued to investigate this important problem, an effort that led him to devise a therapeutic strategy for the treatment of EBS and related disorders. The innovative therapy uses a natural product commonly found in the diet.

Lab

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.

Lab Website: Pierre Coulombe Laboratory

Selected Publications

View all on Pubmed

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. Nat. Genet. 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. J. Cell Biol. 208(5):613-27.

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(10): 910-14.

Kim S, Wong P, Coulombe PA (2006). Interaction of keratin 17 with 14-3-3 regulates protein synthesis and epithelial cell growth. Nature 441: 362-5.

Coulombe PA, Hutton ME, Letai A, Paller AS, Hebert A, Fuchs E (1991): Point mutations in human K14 genes of epidermolysis bullosa simplex patients: Genetic and functional analyses. Cell 66: 1301-1311.

Academic Affiliations & Courses

Graduate Program Affiliation

Graduate Program in Cellular and Molecular Medicine

Activities & Honors

Honors

  • Inaugural Mary Schwartz Lecture in Skin Biology, University of Dundee, 2013
  • Irwin M. Freedberg Memorial Lecture, Gordon Research Conference on Epithelial Differentiation, 2013
  • Elected Fellow, Section of Biological Sciences, Amer. Assoc. Adv. Sciences, 2009
  • 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, 2008
  • Teacher of the Year, J.H.U. Graduate Student Association, 2000
  • Junior Faculty Research Award , American Cancer Society, 1995 - 1997
  • James A. Shannon Director’s Award , National Institutes of Health, 1994 - 1995
  • Thomas B. Fitzpatrick Research Award in Dermatology, 1992
  • Centennial Fellowship Award , Medical Research Council of Canada, 1989 - 1992
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