Education:
DVM 1975 Veterinary Medcine - Nippon Vet.and Animal Sci. University, Tokyo, Japan
MS 1980 Comparative Pathology - University of California, Davis
PhD 1989 Cell Biology - Kobe University School of Medicine, Kobe, Japan
Postdoctoral Research Fellowship:
1981 - 1983 University of California, Davis
Started at USC: 1994 Research Topics: Diabetes/Metabolic Diseases
Research Description
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.
10 Selected Publications:
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Mann J,Chu DC,Maxwell A,Oakley F,Zhu NL,Tsukamoto H,Mann DA - MeCP2 controls an epigenetic pathway that promotes myofibroblast transdifferentiation and fibrosis. - Gastroenterology [2009] Oct 17;(): PubMed
Yeligar SM,Machida K,Tsukamoto H,Kalra VK - Ethanol augments RANTES/CCL5 expression in rat liver sinusoidal endothelial cells and human endothelial cells via activation of NF-kappaB, HIF-1alpha, and AP-1. - J Immunol [2009] Nov 1;183(9):5964-76 PubMed
Yeligar S,Tsukamoto H,Kalra VK - Ethanol-induced expression of ET-1 and ET-BR in liver sinusoidal endothelial cells and human endothelial cells involves hypoxia-inducible factor-1alpha and microrNA-199. - J Immunol [2009] Oct 15;183(8):5232-43 PubMed
Zhang AS,Yang F,Wang J,Tsukamoto H,Enns CA - Hemojuvelin-Neogenin Interaction Is Required for Bone Morphogenic Protein-4-induced Hepcidin Expression. - J Biol Chem [2009] Aug 21;284(34):22580-9 PubMed
Lu SC,Ramani K,Ou X,Lin M,Yu V,Ko K,Park R,Bottiglieri T,Tsukamoto H,Kanel G,French SW,Mato JM,Moats R,Grant E - S-adenosylmethionine in the chemoprevention and treatment of hepatocellular carcinoma in a rat model. - Hepatology [2009] Apr 6;(): PubMed
Tsukamoto H,Machida K,Dynnyk A,Mkrtchyan H - "Second hit" models of alcoholic liver disease. - Semin Liver Dis [2009] May;29(2):178-87 PubMed
Gao J,Chen J,Kramer M,Tsukamoto H,Zhang AS,Enns CA - Interaction of the hereditary hemochromatosis protein HFE with transferrin receptor 2 is required for transferrin-induced hepcidin expression. - Cell Metab [2009] Mar;9(3):217-27 PubMed
Boros LG,Deng Q,Pandol SJ,Tsukamoto H,Go VL,Lee WN - Ethanol diversely alters palmitate, stearate, and oleate metabolism in the liver and pancreas of rats using the deuterium oxide single tracer. - Pancreas [2009] Mar;38(2):e47-52 PubMed
Tatsukawa H,Fukaya Y,Frampton G,Martinez-Fuentes A,Suzuki K,Kuo TF,Nagatsuma K,Shimokado K,Okuno M,Wu J,Iismaa S,Matsuura T,Tsukamoto H,Zern MA,Graham RM,Kojima S - Role of Transglutaminase 2 in Liver Injury via Crosslinking and Silencing of Transcription Factor, Sp1. - Gastroenterology [2009] Jan 14;(): PubMed
Miyagawa T,Mochizuki Y,Nakahara Y,Kawamura T,Sasaki S,Tsukamoto H,Tabata H,Okada H - [A case of drug-induced pneumonitis due to Sai-rei-to] - Nihon Kokyuki Gakkai Zasshi [2009] Jan;47(1):47-51 PubMed
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