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.

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.

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.

                                                 

Meet Pierre Coulombe

Dr. Coulombe was born and raised in Montréal, Canada. He has been studying epithelial biology from the perspective of keratin regulation and function since 1988, when he joined Elaine Fuchs’ laboratory at the University of Chicago for postdoctoral training. In that latter capacity Dr. Coulombe played a key role in the discovery of the structural support function of keratin intermediate filaments in vivo, along with the first set of mutations in an intermediate filament gene (keratin 14), causing epidermolysis bullosa simplex (EBS).

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.

In parallel, his laboratory uncovered and characterized several novel, non-canonical functions for keratin proteins in studies focused on the wound-repair associated keratins – i.e., the K6 paralogs, K16 and K17 – whose expression is also markedly elevated in acute and chronic inflammatory skin conditions and in cancer. Key contributions from the laboratory include the discovery and characterization of roles for keratin proteins in regulating: i) protein synthesis and cell growth; ii) keratinocyte migration; iii) keratinocyte-based innate and acquired immune responses; iv) regulation of gene expression (which, in part, involves a nuclear-localized form of keratin proteins); and v) impacting the course of tumorigenesis in vivo and of tumor cell properties ex vivo.

 

Over the past several years, the study of tumorigenesis and other chronic skin conditions has become a dominant theme of the research being pursued in the Coulombe laboratory.

Recent Publications

Randomized, split-body, single-blinded clinical trial of topical broccoli sprout extract: Assessing the feasibility of its use in keratin-based disorders.

Kerns ML, Guss L, Fahey J, Cohen B, Hakim JM, Sung S, Lu RG, Coulombe PA.

J Am Acad Dermatol. 2016 Nov 23. pii: S0190-9622(16)30900-8. doi: 10.1016/j.jaad.2016.10.009. [Epub ahead of print]

Loss of Keratin 17 induces tissue-specific cytokine polarization and cellular differentiation in HPV16-driven cervical tumorigenesis in vivo.

Hobbs RP, Batazzi AS, Han MC, Coulombe PA.

Oncogene. 2016 Oct 27;35(43):5653-5662. doi: 10.1038/onc.2016.102.

Discovery of keratin function and role in genetic diseases: the year that 1991 was.

Coulombe PA.

Mol Biol Cell. 2016 Sep 15;27(18):2807-10. doi: 10.1091/mbc.E15-09-0625.

Keratins Are Going Nuclear.

Hobbs RP, Jacob JT, Coulombe PA.

Dev Cell. 2016 Aug 8;38(3):227-33. doi: 10.1016/j.devcel.2016.07.022.

Oxidative stress and dysfunctional NRF2 underlie pachyonychia congenita phenotypes.

Kerns ML, Hakim JM, Lu RG, Guo Y, Berroth A, Kaspar RL, Coulombe PA.

J Clin Invest. 2016 Jun 1;126(6):2356-66. doi: 10.1172/JCI84870.

Skin Keratins.

Wang F, Zieman A, Coulombe PA.

Methods Enzymol. 2016;568:303-50. doi: 10.1016/bs.mie.2015.09.032.

View all on PubMed

Pierre A. Coulombe, Ph.D.

Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health

Joint Appointments in Biological Chemistry, Dermatology and Oncology at the School of Medicine

Epithelial Homeostasis in Health and Disease

COPYRIGHT © Dr. Pierre Coulombe 2020