The gastrointestinal epithelium plays a central role in maintaining and coordinating mucosal homeostasis and immunity. Intestinal epithelial barrier compromise in mucosal wounds is seen in many pathologic states that encompass inflammatory bowel diseases, ischemia, mechanical injury and surgical procedures. Coordinated epithelial cell migration and proliferation required for wound closure is a complex process that is not well understood. Our overarching hypothesis is that epithelial and immune cell mediators in the intestinal mucosa coordinate epithelial repair responses. Thus, the proposed studies will identify and characterize mechanisms by which lipid and protein mediators in the intestinal mucosa promote wound repair. Knowledge gained from these studies in the short term will provide a better understanding of basic mechanisms by which inflammatory cell and epithelial mediators control intestinal epithelial homeostasis and mucosal wound repair. In the long term these studies will aid in the development of new therapeutic strategies aimed at promoting intestinal mucosal wound repair.
The lining of the gastrointestinal tract plays an important role in immune defense, which can be significantly compromised by conditions such as inflammatory bowel diseases, ischemia, mechanical injury and surgical procedures. This grant will address mechanisms by which the mucosal lining heals after such damage. Knowledge gained from these studies in the short term will provide a better understanding of basic mechanisms by which wound healing is controlled, and in the long term, these studies will aid in the development of new therapeutic strategies aimed at promoting mucosal wound repair.
|Cruz-Acuña, Ricardo; Quirós, Miguel; Farkas, Attila E et al. (2017) Synthetic hydrogels for human intestinal organoid generation and colonic wound repair. Nat Cell Biol 19:1326-1335|
|Garcia-Hernandez, Vicky; Quiros, Miguel; Nusrat, Asma (2017) Intestinal epithelial claudins: expression and regulation in homeostasis and inflammation. Ann N Y Acad Sci 1397:66-79|
|Kudelka, Matthew R; Hinrichs, Benjamin H; Darby, Trevor et al. (2016) Cosmc is an X-linked inflammatory bowel disease risk gene that spatially regulates gut microbiota and contributes to sex-specific risk. Proc Natl Acad Sci U S A 113:14787-14792|
|Gómez-Suárez, M; Gutiérrez-Martínez, I Z; Hernández-Trejo, J A et al. (2016) 14-3-3 Proteins regulate Akt Thr308 phosphorylation in intestinal epithelial cells. Cell Death Differ 23:1060-72|
|Medina-Contreras, Oscar; Harusato, Akihito; Nishio, Hikaru et al. (2016) Cutting Edge: IL-36 Receptor Promotes Resolution of Intestinal Damage. J Immunol 196:34-8|
|Luissint, Anny-Claude; Parkos, Charles A; Nusrat, Asma (2016) Inflammation and the Intestinal Barrier: Leukocyte-Epithelial Cell Interactions, Cell Junction Remodeling, and Mucosal Repair. Gastroenterology 151:616-32|
|Butin-Israeli, Veronika; Houser, Madelyn C; Feng, Mingli et al. (2016) Deposition of microparticles by neutrophils onto inflamed epithelium: a new mechanism to disrupt epithelial intercellular adhesions and promote transepithelial migration. FASEB J 30:4007-4020|
|Matthews, Jason D; Sumagin, Ronen; Hinrichs, Benjamin et al. (2016) Redox control of Cas phosphorylation requires Abl kinase in regulation of intestinal epithelial cell spreading and migration. Am J Physiol Gastrointest Liver Physiol 311:G458-65|
|Leoni, Giovanna; Nusrat, Asma (2016) Annexin A1: shifting the balance towards resolution and repair. Biol Chem 397:971-9|
|Lili, Loukia N; Farkas, Attila E; Gerner-Smidt, Christian et al. (2016) Claudin-based barrier differentiation in the colonic epithelial crypt niche involves Hopx/Klf4 and Tcf7l2/Hnf4-? cascades. Tissue Barriers 4:e1214038|
Showing the most recent 10 out of 63 publications