Hidekazu (Hide) Tsukamoto


Keck School of Medicine

Research Topics

  • Diabetes/Metabolic Diseases

Research Overview

Role of Iron in Activation of NF-kB in Hepatic Macrophages in Liver Injury: This study investigates how a chelatable pool of intracellular iron participates in signal transduction leading to activation of NF-kB, a critical transcription factor for expression of pro-inflammatory genes (cytokines, adhesion molecules, iNOS), in hepatic macrophages.

Role of Paroxisome Proliferator Activated Receptor-gamma (PPAR-gamma) in Activation of Hepatic Stellate Cells and Macrophages: This project investigates the molecular mechanisms by which decreased activity of PPAR-gamma has a permissive role in fibroproliferative activation of hepatic stellate cells (HSC) and upregulation of pro-inflammatory genes by hepatic macrophages in liver injury. Diminished cross-coupling of PPAR-gamma with other transcription factors such as NF-kB, AP-1 and STAT, is the main theme of the project.

IL-10 in Liver Fibrogenesis: This project tests a hypothesis that the failure for hepatic stellate cells to maintain IL-10 expression, underlies pathologic progression to liver cirrhosis. An autocrine self-regulation of hepatic stellate cells by IL-10, has recently been identified by us in experimental liver fibrosis. Our in vitro and in vivo experiments attempt to define the mechanisms of regulation for expression of IL-10 and its receptors, as well as the biologic significance of this autocrine loop in liver fibrogenesis.

Development of a new generation of bioartificial liver: Based on our years of experiences in biology of non-parenchymal liver cells such as hepatic stellate cells (HSC) and their importance in differentiation of hepatocytes, we are testing a new prototype of bioartificial liver using the radial flow system and co-culture with HSC. We also use thismodel to examine the effects of vector-mediated expression of growth and differentiation factors, as well as hematopictic stem cells.