The Liver Research Center is a 13,000-sq. ft. facility emphasizing molecular biology of liver diseases. Fellows may participate in many of the established studies i.e., genomics, pathogenesis of HCC.
The molecular relationship between chronic hepatitis B, C infection(s) and HCC is under investigation. Of interest is the generation of naturally occurring viral variants which convey different biologic properties i.e., latency, low gene expression, and increased virulence. Ongoing studies examine the molecular mechanisms of viral integration into cellular DNA during the development of HCC with emphasis on HBV variants.
Attempts are underway to understand: hepadnavirus hepatocyte cell surface receptor binding protein, the functional role of hepatitis Bx protein, characterization and cloning of liver specific proteins. All relate to the hepatocyte transformation process since HBx, in combination with cellular factors, acts as a transcriptional transactivator of growth-related genes.
The development of antiviral approaches i.e., antisense oligonucleotides, ribozymes, dominant negative mutants, therapeutic viral DNA-based vaccines, that interfere with HBV/HCV replication. Gene therapy of viral hepatic disease to develop DNA constructs for delivery to the liver i.e., receptor mediated endocytosis of targeted liposomes, and use of various adenoviral, retroviral, and adeno-associated viral constructs that express genes of interest in hepatocytes.
Major work focuses on growth regulation of hepatocytes through factor receptors and intracellular signal transduction pathways i.e., insulin receptor substrate-1 (IRS-1). Downstream MAP kinase activation is being studied in a variety of experimental and human disease systems. Finally, the relationship of chronic HBV infection and activation of growth factor signal transduction cascade is actively pursued at the molecular level.
Finally, we also focus on 1) mechanisms of alcohol and nonalcoholic fatty liver disease that alters liver injury and repair 2) translational research involving early diagnosis and therapy of gastrointestinal and liver tumors, using monoclonal antibody based technology and phage cancer vaccine constructs and 3) signaling pathways important in cell growth and transformation with particular emphasis on the hepatic insulin signaling cascade.