External Seminar: Andrew NEISH
Oct 01, 2018
from 11:00 to 12:00
|Where||1 place de l'école|
|Contact Name||François Leulier|
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Next week we will have the pleasure to host Pr Andrew Neish from Emory University, Atlanta, US. Andy is an expert of epithelial biology, especially in the intestine in the context of Host-Microbes interactions and uses mouse and fly models. His talk is entitled: Regulation of Epithelial Homeostasis by the Microbiota You'll find below an abstract of his work and a list of some of his important papers.
The resident prokaryotic microbiota of the intestine can influence normal gut proliferation, development, growth and response to injury. We describe a common paradigm wherein contact of prokaryotic organisms stimulate the enzymatic generation of reactive oxygen species (ROS) in the host epithelia in organisms as disparate as flies and mice. These events occur via the action of highly conserved NADPH oxidase enzymes (dNox in Drosophila and Nox1 in mammals). Interestingly, a subset of bacterial taxa, predominately Lactobacilli, potently stimulates Nox dependent ROS generation in both systems, and activates redox responsive transcriptional circuits, including the Nrf2/Keap pathway. Germ-free mice and flies exhibit reduced epithelial proliferation and increased sensitivity to tissue damage. Consistently, epithelial-specific Nox1 and Nrf2 null mice, and dNox and CnC (Nrf2 ortholog in flies) mutant Drosophila demonstrate aberrant intestinal stem cell dynamics and responses to injury. Conversely, commensal bacteria such as the Lactobacilli and Akkermansia accelerate epithelial cell movement and mucosal restitution mice and flies, and correct proliferative defects observed in germ-free animals, in a Nox1 and Nrf2 dependent fashion. At the tissue level, bacterially induced ROS generation is strikingly excluded from discrete stem cell niches, resulting in a redox gradient across stem cell compartments in both mice and flies that is absent in germ-free animals. Ectopic generation of ROS in enterocytes outside the stem cell niche phenocopied the effects of the natural microbiota. These data suggest how discrete taxa of bacterial symbionts utilize spatially compartmentalized generation of ROS for controlling highly conserved signaling events that regulate intestinal development and homeostasis
Serum Amyloid A1 Is an Epithelial Prorestitutive Factor.
Hinrichs BH, Matthews JD, Siuda D, O'Leary MN, Wolfarth AA, Saeedi BJ, Nusrat A, Neish AS.
Am J Pathol. 2018 Apr;188(4):937-949. doi: 10.1016/j.ajpath.2017.12.013. Epub 2018 Jan 31.
- PMID: 29366677
Redox control of Cas phosphorylation requires Abl kinase in regulation of intestinal epithelial cell spreading and migration.
Matthews JD, Sumagin R, Hinrichs B, Nusrat A, Parkos CA, Neish AS.
Am J Physiol Gastrointest Liver Physiol. 2016 Sep 1;311(3):G458-65. doi: 10.1152/ajpgi.00189.2016. Epub 2016 Jul 14.
The microenvironment of injured murine gut elicits a local pro-restitutive microbiota.
Alam A, Leoni G, Quiros M, Wu H, Desai C, Nishio H, Jones RM, Nusrat A, Neish AS.
Nat Microbiol. 2016 Jan 27;1:15021. doi: 10.1038/nmicrobiol.2015.21.
- PMID: 27571978
Lactobacilli Modulate Epithelial Cytoprotection through the Nrf2 Pathway.
Jones RM, Desai C, Darby TM, Luo L, Wolfarth AA, Scharer CD, Ardita CS, Reedy AR, Keebaugh ES, Neish AS.
Cell Rep. 2015 Aug 25;12(8):1217-25. doi: 10.1016/j.celrep.2015.07.042. Epub 2015 Aug 13.
- PMID: 26279578
Redox signaling regulates commensal-mediated mucosal homeostasis and restitution and requires formyl peptide receptor 1.
Alam A, Leoni G, Wentworth CC, Kwal JM, Wu H, Ardita CS, Swanson PA, Lambeth JD, Jones RM, Nusrat A, Neish AS.
Mucosal Immunol. 2014 May;7(3):645-55. doi: 10.1038/mi.2013.84. Epub 2013 Nov 6.
- PMID: 24192910
Symbiotic lactobacilli stimulate gut epithelial proliferation via Nox-mediated generation of reactive oxygen species.
Jones RM, Luo L, Ardita CS, Richardson AN, Kwon YM, Mercante JW, Alam A, Gates CL, Wu H, Swanson PA, Lambeth JD, Denning PW, Neish AS.
EMBO J. 2013 Nov 27;32(23):3017-28. doi: 10.1038/emboj.2013.224. Epub 2013 Oct 18.
- PMID: 24141879
Enteric commensal bacteria potentiate epithelial restitution via reactive oxygen species-mediated inactivation of focal adhesion kinase phosphatases.
Swanson PA 2nd, Kumar A, Samarin S, Vijay-Kumar M, Kundu K, Murthy N, Hansen J, Nusrat A, Neish AS.
Proc Natl Acad Sci U S A. 2011 May 24;108(21):8803-8. doi: 10.1073/pnas.1010042108. Epub 2011 May 9.