{"id":77918,"date":"2021-06-21T17:33:29","date_gmt":"2021-06-21T15:33:29","guid":{"rendered":"https:\/\/cri1149.fr\/actuetu\/they-defend-their-thesis\/"},"modified":"2021-06-21T17:33:29","modified_gmt":"2021-06-21T15:33:29","slug":"they-defend-their-thesis","status":"publish","type":"post","link":"https:\/\/cri1149.fr\/en\/news\/they-defend-their-thesis\/","title":{"rendered":"They defend their thesis"},"content":{"rendered":"

\"\"<\/a><\/p>\n

DAN LIU\u00a0<\/span><\/strong><\/p>\n

Title<\/strong>: The role and regulation of NADPH oxidase 1 in intestinal inflammation<\/span><\/p>\n

Defense date<\/strong>: 2021-06-30<\/p>\n

Abstract<\/strong>:<\/p>\n

\n

NADPH oxidases (or NOXs) are a unique family of enzymes dedicated to the production of reactive oxygen species (ROS). NOX1, predominantly expressed in colon epithelial cells, has emerged as a prime regulator of mucosal immunity and inflammation. It is a multicomponent enzyme composed of the transmembrane proteins, NOX1 and p22PHOX<\/sup><\/em>, and the cytosolic proteins, NOXO1, NOXA1, and Rac1. However, dysfunction of NOX1 could be linked to pathological situations in the colon such as inflammatory bowel diseases (IBD). The exact mechanisms through which NOX1 impacts mucosal immunity and inflammation, as well as its regulation in inflammatory conditions, are still unclear.<\/p>\n

In this context, the objectives of my thesis were: 1) to decipher the mechanisms through which NOX1 contributes to mucosal immunity and inflammation 2) to identify new regulators of NOX1 in inflammatory conditions.<\/p>\n

My first work reveals that NOX1-derived ROS drive the expression of bacteriostatic lipocalin-2 (LCN-2) in colonic epithelial cells co-stimulated with TNF-\u03b1 and IL-17, and that the underlying mechanisms involve a p38MAPK-JNK\/ NOXO1\/IkB\u03b6 axis. Furthermore, LCN-2 production and colon damage were decreased in NOX1-deficient mice during TNBS-induced colitis. Finally, analyses of biopsies from patients with Crohn’s disease showed increases in JNK1\/2 activation and NOXO1 and LCN-2 expression.\u00a0 Therefore, NOX1 might play a key role in mucosal immunity and inflammation by controlling LCN-2 expression. (Mucosal Immunology, listed as co-first author)<\/p>\n

My second work identified protein kinase CK2 as a novel regulator of NOX1. CK2 limits NOX1 activity via NOXO1 binding and phosphorylation in colonic epithelial cells and lessens experimental colitis. Loss of CK2 activity during acute colitis results into excessive ROS production, contributing to pathogenesis. Therefore, CK2 acts as a molecular brake to control NOX1 activation and loss of this brake during acute colitis may result in excessive ROS production contributing to pathogenesis. (Submitted, first author)<\/p>\n

Taken together our data uncovered a new function of NOX1-derived ROS in controlling LCN-2 expression and identified CK2 as a novel negative regulator of NOX1 activity in inflammatory situations. Furthermore, dysregulation of these processes may contribute to pathological situations. Strategies to attenuate NOX1 activity or to activate CK2 could be novel therapeutic approaches in IBD.<\/p>\n<\/blockquote>\n

\n

Composition of jury<\/strong> :<\/p>\n

Dr. Fr\u00e9d\u00e9ric Barreau\u00a0\u00a0\u00a0 \u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 CR, HDR, Universit\u00e9 Toulouse\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 \u00a0\u00a0\u00a0 Rapporteur<\/p>\n

Pr. Herve Kovacic\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 PU, Universit\u00e9 Aix-Marseille\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 \u00a0\u00a0\u00a0 Rapporteur<\/p>\n

\u00a0 Dr. Corinne Dupuy\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 DR, Universit\u00e9 Paris-Saclay\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0Examinatrice<\/p>\n

\u00a0Dr. Mariano A. Ostuni\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0PU, Universit\u00e9 de Paris\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 Examinateur<\/p>\n

\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0Dr. Pham My-Chan DANG\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 DR, Universit\u00e9 de Paris\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0Directrice de th\u00e8se.<\/p>\n<\/div>\n

\u00a0<\/div>\n
\n
\n<\/div>\n","protected":false},"excerpt":{"rendered":"

DAN LIU\u00a0 Title: The role and regulation of NADPH oxidase 1 in intestinal inflammation Defense date: 2021-06-30 Abstract: NADPH oxidases (or NOXs) are a unique family of enzymes dedicated to […]<\/p>\n","protected":false},"author":9,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_EventAllDay":false,"_EventTimezone":"","_EventStartDate":"","_EventEndDate":"","_EventStartDateUTC":"","_EventEndDateUTC":"","_EventShowMap":false,"_EventShowMapLink":false,"_EventURL":"","_EventCost":"","_EventCostDescription":"","_EventCurrencySymbol":"","_EventCurrencyCode":"","_EventCurrencyPosition":"","_EventDateTimeSeparator":"","_EventTimeRangeSeparator":"","_EventOrganizerID":[],"_EventVenueID":[],"_OrganizerEmail":"","_OrganizerPhone":"","_OrganizerWebsite":"","_VenueAddress":"","_VenueCity":"","_VenueCountry":"","_VenueProvince":"","_VenueState":"","_VenueZip":"","_VenuePhone":"","_VenueURL":"","_VenueStateProvince":"","_VenueLat":"","_VenueLng":"","_VenueShowMap":false,"_VenueShowMapLink":false,"footnotes":""},"categories":[327],"tags":[],"class_list":["post-77918","post","type-post","status-publish","format-standard","hentry","category-news"],"acf":[],"yoast_head":"\nThey defend their thesis - 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