gastroenterologist-2016_keynote

2 / 5

Volume 6, Issue 4(Suppl) J Gastrointest Dig Syst 2016
ISSN:2161-069X JGDS, an open access journal
Page 10
Gastro 2016
August 11-12, 2016
conferenceseries.com
August 11-12, 2016 Birmingham, UK
6th Global Gastroenterologists Meeting
Nathalie Rivard, J Gastrointest Dig Syst 2016, 6:4(Suppl)
Epithelial SHP-2 protects the intestinal mucosa against colitis and colorectal cancer
S HP-2 is a Src homology 2 containing protein tyrosine phosphatase (PTP) expressed in most embryonic and adult tissues.
SHP-2 regulates many cellular functions including growth, differentiation, innate immune response, chemotaxis and
survival. Genetic and biochemical evidence demonstrate that SHP-2 can regulate major signalling pathways including the
RAS/MAPK, PI3K/Akt and JAK/STAT pathways. Interestingly, variations within the human gene locus encoding SHP-2
have been associated with increased susceptibility to develop ulcerative colitis. We thus, analyzed the role of SHP-2 in the
intestine by first generating mice with an intestinal epithelial cell (IEC)-specific deletion of SHP-2 expression (SHP-2IEC-KO
mice). Interestingly, these mice rapidly developed inflammation one month after birth, with clinical and histopathological
features similar to ulcerative colitis. Alterations in Goblet/Paneth cell ratio were observed two weeks after birth, before the
onset of inflammation and were associated with significant alterations in microbiota composition. With age, SHP-2 mice
developed colitis-associated adenocarcinomas. To further analyze the protective role of SHP-2 in the intestinal epithelium,
we also generated mice expressing a constitutive active form of SHP-2 specifically in IECs (SHP-2IEC-E76K mice). These mice
were either challenged with dextran sulfate sodium (DSS) to induce chemical colitis or with Citrobacter rodentium to induce
infectious colitis. Results showed that SHP-2IEC-E76K mice were resistant to DSS treatment or C. rodentium infection.Thus, SHP-2
activation exerts protective actions against mucosal damage and during infection with an A/E (attaching and effacing) bacterial
pathogen. Finally, we found reduced SHP-2 expression in intestinal biopsies from patients with active colitis, emphasizing the
inverse relationship between SHP-2 expression and colonic inflammatory phenotype. Overall, our results indicate that SHP-2
maintains barrier function in the colon and thereby, helps to prevent spontaneous microbiota-driven inflammation and colitis-
associated cancer development.
Biography
Nathalie Rivard received her PhD from Universite de Sherbrooke in 1994 and completed a 3.5 year Post-doctorate at the Centre de Biochimie-CNRS, Université
de Nice, France with Dr. J Pouysségur in 1997. Then, she accepted a faculty position in the Department of Anatomy and Cell Biology at the Faculté de Médecine
et des Sciences de la santé de l’Université de Sherbrooke. Since 2008, she is the Chair of the Department of Anatomy and Cell Biology and Chair of the
Cancer Axis at Université de Sherbrooke. Her research focuses on the analysis of signalling pathways that control proliferation, differentiation, tumorigenesis and
inflammatory response of intestinal epithelial cells. She has published more than 80 papers in reputed journals. She is the recipient of 2013 Canadian Association
of Gastroenterology Research Excellence Award and holds a Canada Research Chair.
Nathalie Rivard
Universite de Sherbrooke, Sherbrooke, Canada