The scope of our research is to evaluate therapeutic strategies to enhance liver regeneration and repair that could aid in improving patients'outcomes in the setting of liver transplantation using marginal liver graft, as well as extended liver resection for cancer that are at higher risk for primary non-function and acute hepatic failure. Our team utilizes genomic, proteomic, and metabolomic platforms to study liver regeneration and identify novel therapeutic targets to improve outcomes. The focus of our laboratories is to develop state-of-the-art gene therapy platforms to deliver the hepatoprotective and liver regenerative gene A20.
We uncovered a potent hepatoprotective function for A20, also called TNFAIP3, through its combined anti-inflammatory, anti-apoptotic, and proliferative functions in hepatocytes. Liver targeted A20 gene therapies protected from lethality in mouse models of toxic hepatitis, extended 78%and lethal radical hepatectomies 90%and also prolonged liver ischemia. Recent promising pre-translational studies in large animal prelude clinical translation of this therapy.
This protocol offers a unique surgical model designed for investigating small for size syndrome, as well as assessing therapeutic strategies to improve outcomes of extensive hepatectomies for cancer, and increase successful rates of marginal and extended criteria liver grafts. When the 78%hepatectomy is performed correctly, this procedure results in approximately 50%postoperative survival as opposed to nearly 100%survival associated with the classical 2/3 partial hepatectomy in healthy mice.
