Activating the Hippo pathway effector YAP to augment liver regeneration
Grant Project Details:
The goal of this proposal is to speed up liver regeneration by activation a regeneration pathway with a drug treatment. This will be tested in multiple models, including models in which regeneration is not as good at baseline. Positive results would provide a potential treatment to improve liver function in patients suffering from liver failure.
With this proposal we are evaluating the ability to improve the regeneration of the liver following surgical removal of a portion of it with two separate medications. Our hope is that positive results will give us both further insight into what the mechanisms are that regulate liver regeneration in patients that have had a portion of their liver removed, but also positive results from the drug studies could provide the preclinical data necessary to pursue human trials of these treatments. Our studies are currently on track. In the first year we have completed testing of the compounds in cells and have completed several studies in mouse models of liver surgery. The results have been encouraging. In the second year we will complete the studies in mouse models of fatty liver disease, a common condition in the United States that limits the ability of the liver to regenerate.