Imperial College London

DrRachaelBarry

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Imperial College Research Fellow
 
 
 
//

Contact

 

r.barry Website

 
 
//

Location

 

Commonwealth BuildingCommonwealth BuildingHammersmith Campus

//

Summary

 

Publications

Publication Type
Year
to

10 results found

Joseph SR, Lum B, Banushi B, Barry R, Panizza B, Walpole E, Simpson Fet al., 2020, Antibody/Ligand-Target Receptor Internalization Assay Protocol Using Fresh Human or Murine Tumor Ex Vivo Samples, STAR Protocols, Vol: 1, Pages: 100087-100087, ISSN: 2666-1667

Journal article

Chew HY, De Lima PO, Cruz JLG, Banushi B, Echejoh G, Hu L, Joseph SR, Lum B, Rae J, O'Donnell JS, de Long LM, Okano S, King B, Barry R, Moi D, Mazzieri R, Thomas R, Souza-Fonseca-Guimaraes F, Foote M, McCluskey A, Robinson PJ, Frazer IH, Saunders NA, Parton RG, Dolcetti R, Cuff K, Martin JH, Panizza B, Walpole E, Wells JW, Simpson Fet al., 2020, Endocytosis Inhibition in Humans to Improve Responses to ADCC-Mediating Antibodies, CELL, Vol: 180, Pages: 895-+, ISSN: 0092-8674

Journal article

Carson D, Barry R, Eve GD H, Roumeliotis T, García-Weber D, Mullineaux Sanders C, Elinav E, Arrieumerlou C, Choudhary J, Frankel Get al., 2020, Citrobacter rodentium induces rapid and unique metabolic and inflammatory responses in mice suffering from severe disease, Cellular Microbiology, Vol: 22, Pages: 1-17, ISSN: 1462-5814

The mouse pathogen Citrobacter rodentium is used to model infections with enterohaemorrhagic and enteropathogenic Escherichia coli (EHEC and EPEC). Pathogenesis is commonly modelled in mice developing mild disease (e.g., C57BL/6). However, little is known about host responses in mice exhibiting severe colitis (e.g., C3H/HeN), which arguably provide a more clinically relevant model for human paediatric enteric infection. Infection of C3H/HeN mice with C. rodentium results in rapid colonic colonisation, coinciding with induction of key inflammatory signatures and colonic crypt hyperplasia. Infection also induces dramatic changes to bioenergetics in intestinal epithelial cells, with transition from oxidative phosphorylation (OXPHOS) to aerobic glycolysis and higher abundance of SGLT4, LDHA, and MCT4. Concomitantly, mitochondrial proteins involved in the TCA cycle and OXPHOS were in lower abundance. Similar to observations in C57BL/6 mice, we detected simultaneous activation of cholesterol biogenesis, import, and efflux. Distinctly, however, the pattern recognition receptors NLRP3 and ALPK1 were specifically induced in C3H/HeN. Using cell‐based assays revealed that C. rodentium activates the ALPK1/TIFA axis, which is dependent on the ADP‐heptose biosynthesis pathway but independent of the Type III secretion system. This study reveals for the first time the unfolding intestinal epithelial cells' responses during severe infectious colitis, which resemble EPEC human infections.

Journal article

Barry R, Ruano-Gallego D, Radhakrishnan ST, Lovell S, Yu L, Kotik O, Glegola-Madejska I, Tate EW, Choudhary JS, Williams HRT, Frankel Get al., 2020, Faecal neutrophil elastase-antiprotease balance reflects colitis severity, Mucosal Immunology, Vol: 13, Pages: 322-333, ISSN: 1933-0219

Given the global burden of diarrheal diseases on healthcare it is surprising how little is known about the drivers of disease severity. Colitis caused by infection and inflammatory bowel disease (IBD) is characterised by neutrophil infiltration into the intestinal mucosa and yet our understanding of neutrophil responses during colitis is incomplete. Using infectious (Citrobacter rodentium) and chemical (dextran sulphate sodium; DSS) murine colitis models, as well as human IBD samples, we find that faecal neutrophil elastase (NE) activity reflects disease severity. During C. rodentium infection intestinal epithelial cells secrete the serine protease inhibitor SerpinA3N to inhibit and mitigate tissue damage caused by extracellular NE. Mice suffering from severe infection produce insufficient SerpinA3N to control excessive NE activity. This activity contributes to colitis severity as infection of these mice with a recombinant C. rodentium strain producing and secreting SerpinA3N reduces tissue damage. Thus, uncontrolled luminal NE activity is involved in severe colitis. Taken together, our findings suggest that NE activity could be a useful faecal biomarker for assessing disease severity as well as therapeutic target for both infectious and chronic inflammatory colitis.

Journal article

Mullineaux-Sanders C, Sanchez-Garrido J, Hopkins EGD, Shenoy AR, Barry R, Frankel Get al., 2019, Citrobacter rodentium-host-microbiota interactions: immunity, bioenergetics and metabolism, NATURE REVIEWS MICROBIOLOGY, Vol: 17, Pages: 701-715, ISSN: 1740-1526

Journal article

Joseph SR, Gaffney D, Barry R, Hu L, Banushi B, Wells JW, Lambie D, Strutton G, Porceddu SV, Burmeister B, Leggatt GR, Schaider H, Dolcetti R, Frazer IH, Saunders NA, Foote M, Soyer HP, Simpson Fet al., 2019, An Ex Vivo Human Tumor Assay Shows Distinct Patterns of EGFR Trafficking in Squamous Cell Carcinoma Correlating to Therapeutic Outcomes, JOURNAL OF INVESTIGATIVE DERMATOLOGY, Vol: 139, Pages: 213-223, ISSN: 0022-202X

Journal article

Barry R, John SW, Liccardi G, Tenev T, Jaco I, Chen CH, Choi J, Kasperkiewicz P, Fernandes-Alnemri T, Alnemri E, Drag M, Chen Y, Meier Pet al., 2018, SUMO-mediated regulation of NLRP3 modulates inflammasome activity, Nature Communications, Vol: 9, ISSN: 2041-1723

The NLRP3 inflammasome responds to infection and tissue damage, and rapidly escalates the intensity of inflammation by activating interleukin (IL)-1β, IL-18 and cell death by pyroptosis. How the NLRP3 inflammasome is negatively regulated is poorly understood. Here we show that NLRP3 inflammasome activation is suppressed by sumoylation. NLRP3 is sumoylated by the SUMO E3-ligase MAPL, and stimulation-dependent NLRP3 desumoylation by the SUMO-specific proteases SENP6 and SENP7 promotes NLRP3 activation. Defective NLRP3 sumoylation, either by NLRP3 mutation of SUMO acceptor lysines or depletion of MAPL, results in enhanced caspase-1 activation and IL-1β release. Conversely, depletion of SENP7 suppresses NLRP3-dependent ASC oligomerisation, caspase-1 activation and IL-1β release. These data indicate that sumoylation of NLRP3 restrains inflammasome activation, and identify SUMO proteases as potential drug targets for the treatment of inflammatory diseases.

Journal article

Plaza-Menacho I, Barnouin K, Barry R, Borg A, Orme M, Chauhan R, Mouilleron S, Martínez-Torres RJ, Meier P, McDonald NQet al., 2016, RET Functions as a Dual-Specificity Kinase that Requires Allosteric Inputs from Juxtamembrane Elements, Cell Reports, Vol: 17, Pages: 3319-3332, ISSN: 2211-1247

Journal article

Hill MM, Daud NH, Aung CS, Loo D, Martin S, Murphy S, Black DM, Barry R, Simpson F, Liu L, Pilch PF, Hancock JF, Parat M-O, Parton RGet al., 2012, Co-Regulation of Cell Polarization and Migration by Caveolar Proteins PTRF/Cavin-1 and Caveolin-1, PLOS ONE, Vol: 7, ISSN: 1932-6203

Journal article

Ashe A, Butterfield NC, Town L, Courtney AD, Cooper AN, Ferguson C, Barry R, Olsson F, Liem KF, Parton RG, Wainwright BJ, Anderson KV, Whitelaw E, Wicking Cet al., 2012, Mutations in mouse Ift144 model the craniofacial, limb and rib defects in skeletal ciliopathies, HUMAN MOLECULAR GENETICS, Vol: 21, Pages: 1808-1823, ISSN: 0964-6906

Journal article

This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.

Request URL: http://wlsprd.imperial.ac.uk:80/respub/WEB-INF/jsp/search-html.jsp Request URI: /respub/WEB-INF/jsp/search-html.jsp Query String: respub-action=search.html&id=00888115&limit=30&person=true