Jonas Cook
Pronouns: he/him/his
Research Mentor(s): Anny-Claude Luissint
Co-Presenter:
Research Mentor School/College/Department: Pathology / Medicine
Presentation Date: April 20
Presentation Type: Oral5
Session: Session 5 – 3:40pm – 4:30 pm
Room: Breakout Room 5
Authors: Jonas Cook, Asma Nusrat, Charles Parkos, Anny-Claude Luissint
Presenter: 4
Abstract
Impaired intestinal barrier function has been associated with chronic intestinal disorders such as ulcerative colitis and Crohn’s disease. At a cellular level, the intestinal mucosal barrier is created by a single layer of intestinal epithelial cells (IEC) which are held together by interactions between transmembrane adhesion proteins on neighboring cells. Cellular cohesion and coordinated collective migration of IEC must be maintained and are crucial for mucosal wound healing after injury and the restoration of epithelial barrier function. CAR-Like Membrane Protein (CLMP) is a transmembrane glycoprotein expressed in IEC. The role of CLMP in intestinal inflammation and mucosal barrier function is unknown. Preliminary studies showed that downregulation of CLMP resulted in weakened cell-cell cohesion, suggesting that CLMP is a positive regulator of barrier function. Additionally, CLMP expression is upregulated in IEC under inflammatory conditions in vitro and vivo. We hypothesized that pro-inflammatory mediators control CLMP expression in IEC which in turn promotes mucosal barrier function. This study used model human IEC expressing CLMP endogenously, and IECs where CLMP expression was silenced or upregulated. To study the role of CLMP in regulating mucosal repair after injury, we used an in vitro scratch-wound healing assay. To assess the effect of pro-inflammatory mediators (such as INF?? and TNF??) on controlling CLMP expression, we used Western blot analysis. Co-immunoprecipitation techniques were used to investigate the candidate partners of CLMP. We validated our preliminary results indicating that CLMP protein expression is regulated by pro-inflammatory mediators. We also found that loss of CLMP resulted in delayed wound repair in vitro, suggesting that it positively regulates intestinal mucosal healing. Lastly, we optimized a co-immunoprecipitation assay to identify CLMP’s interacting partners. Altogether, our results suggest a crucial role for CLMP in the positive regulation of intestinal epithelial barrier function and mucosal repair after injury.
Biomedical Sciences, Interdisciplinary
