Digestive Health Center

  • Chronic Liver Disease

    Mike A. Leonis, MD, PhD
    Assistant Professor
    Department of Pediatrics; Division of Gastroenterology, Hepatology, & Nutrition

    Description of Research

    Dr. Leonis investigates the mechanisms of hepatic tumorigenesis. The long-term goal of his research is to define the role of the tyrosine kinase Ron receptor in liver pathophysiology, focusing primarily on the role of the Ron receptor gain-of-function in hepatic tumorigenesis. He has previously used the well-characterized lipopolysaccharide-induced murine model of acute liver failure in galactosamine-sensitized mice to show that mice containing a deletion in the tyrosine kinase domain of the Ron receptor have a reduction in the number of liver cells undergoing apoptosis compared to wild-type mice. Currently he is testing the hypothesis that gain-of-function of the Ron receptor leads to hepatic tumorigenesis, possibly via activation of the beta-catenin transcriptional cascade. In preliminary experiments to test this hypothesis both in vitro and in vivo, he has established hepatic cell lines that overexpress either the wild type or a constitutively active form of the Ron receptor, and generated a transgenic mouse line with liver-specific overexpression of wild type Ron receptor. In complementary studies, Dr. Leonis investigates the activation of intracellular signaling pathways controlled by the Ron receptor in liver biopsies from patients with hepatoblastoma.  

    Collaborations and Core Use

    Dr. Leonis has used the Integrative Morphology Core in collaboration with Dr. Waltz to study the role of Ron in the hepatic protection against apoptosis. Projection of Core use: Integrative Morphology Core.

 
  • Research image.

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    Research image.

    Hepatic microtumors from transgenic mice overexpressing Ron. Panel A: Immunostaining of transgenic liver using antibodies to Ron receptor. Liver tumor, right of dotted line; uninvolved liver, left of dotted line. Inset: control liver. Panel B: Anti-albumin immunofluorescence in a transgenic liver tumor (right of dotted line) and neighboring normal hepatic parenchyma (left of dotted line). Panels C-E: staining using antibodies to glutamine synthetase (panel C), HNF4a (panel D) and alpha-fetoprotein (panel E). Insets: isotype-specific IgG control. Figure in a manuscript submitted for publication.