Research Interests

The Tsukamoto laboratory has revealed altered cell fate regulation underlies "activation" of hepatic stellate cells and consequent liver fibrogenesis via a series of publications in J Biol Chem from 2000 and 2007. This research led to a recent and novel finding that activated Wnt signaling inhibits "adipogenic" transcriptional regulation in hepatic stellate cells and thereby induces myofibroblastic transdifferentiation in the genesis of liver fibrosis {Am J Physiol, 294:G39-49, 2008). Most recently, this anti-adipogenic regulation is shown to be mediated by epigenetic repression of the master adipogenenic regulator Ppary involving the methyl CpG binding protein MeCP2 and the PRC methyltrasferase EZH2 (Gastroenterology 1 38:;705-14, 1 38:705-14, 2010). Further, the nuclear protein NECDIN is shown to target Wnt10b proximal promoter to induce this anti-adipogenic morphogen which in turn renders epigenetic repression of Ppary (J Biol Chem 285:30463-71,2010). These findings point to the PparTepigenetic repression as a potential target for liver fibrosis. lndeed, their most recent study to be submitted for publication soon, demonstrate certain polyphenols such as rosmarinic acid have the ability to reverse this epigenetic repression via induction of microRNA species and consequent downregulation of MeCP2 andEZH2. These results have formed the basis for a new R01 application submitted in December of 2010.
  • Cellular and molecular mechanisms of cirrhosis
  • Hepatic stellate cell biology
  • Macrophage biology
  • Iron-dependent NF-kB activation
  • PPARgamma and hepatic stellate cell activation
  • Bioartificial liver development


  • Kobe University, PhD, 1988
  • University of California - Davis, MS, 1980


  • American Society for Biochemistry and Molecular Biology
  • American Association for Studies of Liver Diseases
  • American Physiological Society
  • Research Society on Alcoholism
  • American Association of Advancement of Science


  • Zhu N-1, Wang J, Tsukamoto H, Necdin-Wnt pathway causes epigenetic PPARy repression in hepatic stellate cells. J Biol Chem, 285{40):30affi-71, 2010.
  • Subramanian VS, Subramanya SB, Tsukamoto H, and Said HM, Effect of chronic alcohol feeding on physiological and molecular parameters of renalthiamin transport. Am J Physiol Renal Physiol. 2010 Jul;299(1):F28-34. Epub 2010 Apr 28.
  • Machida K, Tsukamoto H, Liu J-C, Han Y-P, Govindarajan S, Shizuo Akira S, Lai MC, Ou J J-H. The c-Jun mediates HCV hepatocarcinogenesis through stat3 and nitric oxide. Hepatology Aug;52(2):480-92, 2010.
  • Ramani K, Yang H, Kuhlenkamp J, Tomasi L, Tsukamoto H, Mato JM, Lu SC. Changes in the Expression of Methionine Adenosyltransferase Genes and S-adenosylmethionine Homeostasis during Hepatic Stellate Cell Activation, Hepatology, Mar;51(3):986-95, 201 0.
  • Esfandiari F, Medici V, Wong D, Jose S, Dolatshahi M, Dayal S, Lentz S, Tsukomoto H, Zhang M, French SW, Halsted CH. Epigenetic regulation of endoplasmic reticulum stress pathways in a genetically altered ethanol-fed mouse model. Hepatology. Mar;513):932-41, 2010.
  • Ciuclan L, Ehnert S, llkavets l, Weng H-1, Gaitantzi H, Tsukamoto H, Ueberham E, Singer MV, Breitkopf K, Dooley S. TGF-B enhances alcohol dependent hepatocyte damage via downregulation of alcohol dehydrogenase L J Hepatol,
    Mar;52(3):407-16, 2410.
  • Mann J, Chu CK, Maxwell A, Oakley F, Tsukamoto H, Mann DA. An epigenetic regulatory circuit controls hepatic stellate cellactivation and the wound-healing response of the injured liver. Gastroenteroloqy, 138:705-14, 2010.
  • Please visit the PIBBS website for more information

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