Unable to make it to Thomas E. Starzl Biomedical Science Tower? Dr. Nejak-Bowen’s lecture will be available via live stream to people with Pitt login credentials by clicking this link (sign in using your Pitt username and password): https://pitt.hosted.panopto.com/Panopto/Pages/Viewer.aspx?id=028d82f1-51d9-4ae7-ac70-ab3d011bae03If you have problems with the video, contact the CSSD help line at 412-624-4357 (4-HELP).
The Wnt/b-catenin signaling pathway has a well-described role in liver physiology and pathology and controls multiple cellular processes through its regulation of target gene expression. In this talk, Nejak-Bowen will discuss her recent findings, which demonstrate that modulation of this pathway alters the progression of certain liver diseases. Wnt/b-catenin signaling regulates expression of heme synthesis and metabolism genes, which could have implications in treatment of porphyrias. Indeed, inhibiting Wnt/b-catenin signaling in a porphyria mouse model alleviated injury and disease progression through decreased production of porphyrin intermediates, along with increased autophagy. The Nejak-Bowen lab also focuses on cholangiopathies, which are chronic, progressive diseases of the biliary tree that result from bile secretory defects or impairment of bile flow. Regardless of etiology, cholangiopathies share common pathologic mechanisms, including inflammation, ductular reaction, fibrosis, and cholestasis, which can, over time, result in cirrhosis or liver failure. Wnt/b-catenin signaling induces expression of biliary markers in hepatocytes, a process known as cellular reprogramming, during sustained cholestasis and injury to the biliary epithelium. These cells may facilitate hepatobiliary repair by contributing to de novo ducts for improving bile flow. Stimulating hepatocyte reprogramming through b-catenin activation increases hepatocyte reprogramming, thus reducing cholestatic injury. Collectively, these findings indicate a novel opportunity to alleviate multiple types of liver diseases through either inhibition or activation of this pathway.