Research Topics
Genomes and Genes | P A CoulombeSummaryAffiliation: Johns Hopkins University Country: USA Publications
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Publications
The 'ins' and 'outs' of intermediate filament organizationP A Coulombe
Dept of Biological Chemistry, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA
Trends Cell Biol 10:420-8. 2000..This dependence upon a combination of extrinsic and intrinsic determinants contributes to distinguish IFs from other fibrous cytoskeletal polymers and is key to their function...- Cytoplasmic intermediate filaments revealed as dynamic and multipurpose scaffoldsPierre A Coulombe
Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Nat Cell Biol 6:699-706. 2004.... - Great promises yet to be fulfilled: defining keratin intermediate filament function in vivoPierre A Coulombe
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Eur J Cell Biol 83:735-46. 2004..Still, detailed studies of the phenotype exhibited by K6 and K17 null mice yielded novel insight into the properties and function of keratin IFs in vivo... - 'Hard' and 'soft' principles defining the structure, function and regulation of keratin intermediate filamentsPierre A Coulombe
Department of Biological Chemistry, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA
Curr Opin Cell Biol 14:110-22. 2002..Keratin filaments undergo complex regulation involving post-translational modifications and interactions with self and with various classes of associated proteins... 
The nonhelical tail domain of keratin 14 promotes filament bundling and enhances the mechanical properties of keratin intermediate filaments in vitroO Bousquet
Department of Biological Chemistry, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA
J Cell Biol 155:747-54. 2001..These data suggest that the tail domain of K14 contributes to the ability of K5-K14 filaments to self-organize into large bundles showing enhanced mechanical resilience in vitro...- Directed expression of keratin 16 to the progenitor basal cells of transgenic mouse skin delays skin maturationR D Paladini
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Cell Biol 142:1035-51. 1998..We conclude that expression of K16 can significantly alter the response of skin keratinocytes to signaling cues, a distinctive property likely resulting from its unique COOH-terminal tail domain... - A 'hot-spot' mutation alters the mechanical properties of keratin filament networksL Ma
Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Nat Cell Biol 3:503-6. 2001..Our results indicate that the fragility of epithelial cells expressing mutant keratin may result from an impaired ability of keratin polymers to be crosslinked into a functional network... - A reporter transgene based on a human keratin 6 gene promoter is specifically expressed in the periderm of mouse embryosS Mazzalupo
Department of Biological Chemistry, The Johns Hopkins University School of Medicine, 725 N Wolfe St, Baltimore, MD 21205, USA
Mech Dev 100:65-9. 2001..A subset of periderm cells, localized to temporary epithelial fusions, is known to contain keratin 6 protein, and we find that these cells also harbor LacZ enzymatic activity... - Introducing a null mutation in the mouse K6alpha and K6beta genes reveals their essential structural role in the oral mucosaP Wong
Department of Biological Chemistry and Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Cell Biol 150:921-8. 2000..These studies demonstrate an essential structural role for K6 isoforms in the oral mucosa, and implicate filiform papillae as being the major stress bearing structures in dorsal tongue epithelium... - The wound repair-associated keratins 6, 16, and 17. Insights into the role of intermediate filaments in specifying keratinocyte cytoarchitectureK McGowan
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Subcell Biochem 31:173-204. 1998 - The two functional keratin 6 genes of mouse are differentially regulated and evolved independently from their human orthologsK Takahashi
Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, USA
Genomics 53:170-83. 1998..These novel findings have important implications for the evolution, regulation, and function of K6 genes in mammalian species... - Towards a molecular definition of keratinocyte activation after acute injury to stratified epitheliaP A Coulombe
Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Biochem Biophys Res Commun 236:231-8. 1997..This article is focused on the process of recruitment of keratinocytes from intact skin tissue at the proximal wound edges to participate in re-epithelialization... 
Increased levels of keratin 16 alter epithelialization potential of mouse skin keratinocytes in vivo and ex vivoM J Wawersik
Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Mol Biol Cell 12:3439-50. 2001..Various lines of evidence suggest that the mechanism(s) involved is complex and not strictly cell autonomous. These findings have important implications for the function of K16 in vivo...- Onset of keratin 17 expression coincides with the definition of major epithelial lineages during skin developmentK M McGowan
Department of Biological Chemistry and Department of Dermatology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Cell Biol 143:469-86. 1998..The pattern of K17 gene expression during development has direct implications for the morphogenesis of skin epithelia, and points to the existence of a molecular relationship between development and wound repair... - The functional diversity of epidermal keratins revealed by the partial rescue of the keratin 14 null phenotype by keratin 16R D Paladini
Departments of Biological Chemistry and Dermatology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Cell Biol 146:1185-201. 1999.... - Keratin 17 expression in the hard epithelial context of the hair and nail, and its relevance for the pachyonychia congenita phenotypeK M McGowan
Departments of Biological Chemistry and Dermatology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
J Invest Dermatol 114:1101-7. 2000..Our data suggest a role for K17 in the formation and maintenance of various skin appendages and directly support the concept that pachyonychia congenita is a disease of the nail bed... - Intermediate filament scaffolds fulfill mechanical, organizational, and signaling functions in the cytoplasmSeyun Kim
Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Genes Dev 21:1581-97. 2007..As this discovery process continues to unfold, a rationale for the large size of this family and the context-dependent regulation of its members is finally emerging... - A transgenic mouse model with an inducible skin blistering disease phenotypeK Takahashi
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Proc Natl Acad Sci U S A 93:14776-81. 1996.... - Loss of keratin 6 (K6) proteins reveals a function for intermediate filaments during wound repairPauline Wong
Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
J Cell Biol 163:327-37. 2003.... - Pairwise assembly determines the intrinsic potential for self-organization and mechanical properties of keratin filamentsSoichiro Yamada
Department of Chemical Engineering, The Johns Hopkins University, Baltimore, MD 21218, USA
Mol Biol Cell 13:382-91. 2002..Our findings underscore the fundamental importance of pairwise polymerization and have implications for the functional significance of keratin sequence diversity... - An ex vivo assay to assess the potential of skin keratinocytes for wound epithelializationStacy Mazzalupo
Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Invest Dermatol 118:866-70. 2002..The assay is quantitative and can successfully detect increases or decreases in epithelialization potential, and can be useful in the characterization of transgenic mouse models... - Intermediate filaments and tissue repairDaryle DePianto
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Exp Cell Res 301:68-76. 2004..Here we review the literature showing that modulation of cytoplasmic IFs occurs rapidly after injury to a variety of tissues and that such changes play an important role in the context of a timely repair response... - Onset of re-epithelialization after skin injury correlates with a reorganization of keratin filaments in wound edge keratinocytes: defining a potential role for keratin 16R D Paladini
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Cell Biol 132:381-97. 1996.... - The co-repressor hairless has a role in epithelial cell differentiation in the skinJoanna M Zarach
Kennedy Krieger Research Institute, Baltimore, MD 21205, USA
Development 131:4189-200. 2004.... - Keratin 17 promotes epithelial proliferation and tumor growth by polarizing the immune response in skinDaryle DePianto
Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA
Nat Genet 42:910-4. 2010..Our findings establish an immunomodulatory role for Krt17 in Hh driven basaloid skin tumors that could impact additional tumor settings, psoriasis and wound repair... - Mouse models of alopecia: identifying structural genes that are baldly neededXuemei Tong
Dept of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Trends Mol Med 9:79-84. 2003..Here we discuss transgenic mouse models that exhibit alopecia as a primary phenotype, resulting from the inactivation of genes encoding structural proteins... - A keratin cytoskeletal protein regulates protein synthesis and epithelial cell growthSeyun Kim
Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Nature 441:362-5. 2006..These findings reveal a new and unexpected role for the intermediate filament cytoskeleton in influencing cell growth and size by regulating protein synthesis... - Keratin function in skin epithelia: a broadening palette with surprising shadesLi Hong Gu
Department of Biological Chemistry, Johns Hopkins University School of Medicine, 725 N Wolfe St, Baltimore, MD 21205, USA
Curr Opin Cell Biol 19:13-23. 2007..Other studies extended the role of keratin proteins in regulating the response to pro-apoptotic signals, and revealed their ability to modulate protein synthesis and cell size in epithelial cells challenged to grow... - Keratin expression provides novel insight into the morphogenesis and function of the companion layer in hair folliclesLi Hong Gu
Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Invest Dermatol 127:1061-73. 2007..These findings provide novel insight into the morphogenesis and properties of the Cl, and raise the distinct possibility that it is an integral part of the IRS compartment... - Contribution of olfactory neural stem cells to tissue maintenance and regenerationCheuk T Leung
Center for Sensory Biology and the Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, 725 N Wolfe Street, PCTB 801, Baltimore, Maryland 21205, USA
Nat Neurosci 10:720-6. 2007..Our data support a new model of adult neurogenesis in which distinct cell populations mediate normal neuronal turnover and neuronal replacement upon traumatic injury... - Reprogramming of keratin biosynthesis by sulforaphane restores skin integrity in epidermolysis bullosa simplexMichelle L Kerns
Department of Biological Chemistry, 725 North Wolfe Street, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Proc Natl Acad Sci U S A 104:14460-5. 2007..Nrf2 induction is brought about by treatment with sulforaphane, a natural product. Sulforaphane thus represents an attractive option for the prevention of skin blistering associated with K14 mutations in EBS... - Hedgehog signaling, keratin 6 induction, and sebaceous gland morphogenesis: implications for pachyonychia congenita and related conditionsLi Hong Gu
Department of Biological Chemistry, Johns Hopkins University School of Medicine, 725 N Wolfe St, Baltimore, MD 21205, USA
Am J Pathol 173:752-61. 2008.... - Overexpressed transient receptor potential vanilloid 3 ion channels in skin keratinocytes modulate pain sensitivity via prostaglandin E2Susan M Huang
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21025, USA
J Neurosci 28:13727-37. 2008..Our results reveal a previously undescribed mechanism for keratinocyte participation in thermal pain transduction through keratinocyte TRPV3 ion channels and the intercellular messenger PGE(2)... - Self-organization of keratin intermediate filaments into cross-linked networksChang Hun Lee
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA
J Cell Biol 186:409-21. 2009..We propose that self-organization is a key determinant of the structural support function of keratin IFs in vivo... - Keratin 16 expression defines a subset of epithelial cells during skin morphogenesis and the hair cycleKelsie M Bernot
Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
J Invest Dermatol 119:1137-49. 2002.... - Exploiting the keratin 17 gene promoter to visualize live cells in epithelial appendages of miceNicholas Bianchi
Predoctoral Program in Human Genetics, McKusick Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 212105, USA
Mol Cell Biol 25:7249-59. 2005..The compact mK17 gene promoter provides a novel tool for appendage-preferred gene expression and manipulation in transgenic mice... - Defining the properties of the nonhelical tail domain in type II keratin 5: insight from a bullous disease-causing mutationLi Hong Gu
Departments of Biological Chemistry and Dermatology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Mol Biol Cell 16:1427-38. 2005..These data provide a mechanistic basis for the cell fragility seen in individuals bearing the K5-1649delG allele, and point to the role of the C-terminal 41 residues in determining K5's assembly properties... - Role for keratins 6 and 17 during wound closure in embryonic mouse skinStacy Mazzalupo
Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Dev Dyn 226:356-65. 2003.... - Wound epithelialization: accelerating the pace of discoveryPierre A Coulombe
Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
J Invest Dermatol 121:219-30. 2003 - A novel mouse type I intermediate filament gene, keratin 17n (K17n), exhibits preferred expression in nail tissueXuemei Tong
Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
J Invest Dermatol 122:965-70. 2004..Depending on the existence of a human ortholog or a functional equivalent, our findings may also provide a molecular explanation for several unusual aspects of hK17-based diseases... - Hairless triggers reactivation of hair growth by promoting Wnt signalingGerard M J Beaudoin
Kennedy Krieger Research Institute and Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Proc Natl Acad Sci U S A 102:14653-8. 2005..This work links HR and Wnt function, providing a model in which HR regulates the precise timing of Wnt signaling required for hair follicle regeneration... - Overcoming functional redundancy to elicit pachyonychia congenita-like nail lesions in transgenic micePauline Wong
Department of Biological Chemistry, Johns Hopkins University School of Medicine, 725 North Wolfe St, Baltimore, MD 21205, USA
Mol Cell Biol 25:197-205. 2005..Our findings point to significant redundancy among the multiple keratins expressed in hair and nail, which can be related to the common ancestry, clustered organization, and sequence relatedness of specific keratin genes... - Skin: an ideal model system to study keratin genes and proteinsKelsie M Bernot
Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Methods Cell Biol 78:453-87. 2004 - Intermediate filament proteins and their associated diseasesM Bishr Omary
From the Department of Medicine, Palo Alto Veterans Affairs Medical Center and Stanford University, Palo Alto, Calif 94304, USA
N Engl J Med 351:2087-100. 2004 - Barrier function in transgenic mice overexpressing K16, involucrin, and filaggrin in the suprabasal epidermisRichard B Presland
J Invest Dermatol 123:603-6. 2004 - MIM/BEG4, a Sonic hedgehog-responsive gene that potentiates Gli-dependent transcriptionChristopher A Callahan
Program in Epithelial Biology and Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA
Genes Dev 18:2724-9. 2004..These data define MIM as both a Shh-responsive gene and a new member of the pathway that modulates Gli responses during growth and tumorigenesis... - A new fold on an old story: attachment of intermediate filaments to desmosomesPierre A Coulombe
Nat Struct Biol 9:560-2. 2002
Research Grants
- 2002 Gordon Research Conf. on Intermediate FilamentsPIERRE COULOMBE; Fiscal Year: 2002..In addition, there will be a special "Perspectives" session and a platform session dedicated to the discussion of posters. ..
- Training Program in Cellular and Molecular MedicinePIERRE COULOMBE; Fiscal Year: 2007..Applicable to SBIR/STTR Only. See instructions. ^ Yes C] No PHS 398 (Rev. 05/01) ' Page 2 ..
- Keratin proteins and non-melanoma skin tumorsPIERRE COULOMBE; Fiscal Year: 2007..We hope that our findings lead to new ideas for the therapeutic management of aggressive and recurring forms of these tumors. ..