Gender	Male
E-mail	arthur.cederbaum@mssm.edu
Education and Training	Ph.D., Rutgers University
	Fellowship, Mount Sinai School of Medicine
	Fellowship, Princeton University
Awards	2008 Mount Sinai Faculty Council Award for Academic Excellence
	2003 Ronald G. Thurman Lectureship Award University of North Carolina
	1993 Outstanding Faculty Achievement Award Basic Sciences
	1990 - 1999 MERIT AWARD NIH/NIAAA
	1990 - 1990, 1991, 1992, 1996, 1999, 2001, 2003 Excellence in Teaching Medical School

Cederbaum Laboratory

Mount Sinai Liver Disease Research Center

Education and Training	Ph.D., Rutgers University
	Fellowship, Mount Sinai School of Medicine
	Fellowship, Princeton University

Dr. Cederbaum is Director of the Cederbaum Laboratory and Co-Director of the Mount Sinai Liver Disease Research Center.

Postdoctoral Fellows: Jian Zhuge, Aparajita Dey, Yongke Lu, Xiadong Wang.

Research Personnel: Jingxiang Boi. Pengfei Gong, Defeng Wu, Andres Caro.

Summary of Research Studies:
The main research efforts are to evaluate the production of an increased state of oxidative stress by ethanol, and the role of reactive oxygen species in the hepatotoxicity produced by ethanol. We are focusing on the ability of ethanol to increase the levels of a cytochrome P450 isoform called CYP2E1, which has been shown to be powerful producer of superoxide radical and H2O2. We have developed stable HepG2 cell lines which over-express CYP2E1 and have shown that ethanol produces cytotoxicity in cells expressing CYP2E1, but not cells lacking CYP2E1. The cytotoxicity is apoptotic in nature and can be prevented by a variety of antioxidants, inhibitors of CYP2E1, caspase 3 inhibitors and transfection with a plasmid which expresses bcl-2. Ethanol toxicity is enhanced by administration of polyunsaturated fatty acids or by iron, which promote lipid peroxidation. Impairment of mitochondrial function is an early step in the CYP2E1 plus ethanol toxicity. The role of calcium in! the overall mechanism of toxicity and up-regulation of protective factors such as glutathione and antioxidants is under evaluation. Protection by adenoviral vectors expressing antioxidant enzymes such as catalase has been demonstrated. We are currently co-incubating our CYP2E1 cell lines with stellate or Kupffer cells to evaluate possible activation of collagen or cytokine production. Reactive oxygen species are detected by ESR spectroscopy but new HPLC spin-trapping methods have been developed which are more sensitive and we are characterizing the utility of these new approaches. A major mechanism by which ethanol enhances the level of CYP2E1 is by stabilizing the enzyme against degradation. We are characterizing this degradation process and the role of the proteasome-ubiquitin system, and molecular chaperones.

Lu Y, Gong P, Cederbaum AI. Pyrazole induced oxidative liver injury independent of CYP2E1/2A5 induction due to Nrf2 deficiency. Toxicology 2008 Oct 30; 252(1-3): 9-16.

Wang X, Cederbaum AI. S-adenosyl-L-methionine decreases the elevated hepatotoxicity induced by Fas agonistic antibody plus acute ethanol pretreatment in mice. Arch Biochem Biophys 2008 Sep; 477(1): 1-11.

Lu Y, Zhuge J, Wang X, Bai J, Cederbaum AI. Cytochrome P450 2E1 contributes to ethanol-induced fatty liver in mice. Hepatology 2008 May; 47(5): 1483-1494.

Wu D, Cederbaum AI. Development and properties of HepG2 cells that constitutively express CYP2E1. Methods Mol Biol 2008; 447: 137-150.

Wu D, Cederbaum A. Cytochrome P4502E1 sensitizes to tumor necrosis factor alpha-induced liver injury through activation of mitogen-activated protein kinases in mice. Hepatology 2008; 47(3): 1005-1017.

Lu Y, Cederbaum AI. CYP2E1 and oxidative liver injury by alcohol. Free Radic Biol Med 2008 Mar 1; 44(5): 72.

Wang X, Cederbaum AI. Acute ethanol pretreatment increases FAS-mediated liver injury in mice: role of oxidative stress and CYP2E1-dependent and -independent pathways. Free Radic Biol Med 2007 Apr 1; 42(7): 971-984.

Dey A, Caro AA, Cederbaum AI. S-adenosyl methionine protects ob/ob mice from CYP2E1-mediated liver injury. Am J Physiol Gastrointest Liver Physiol 2007 July; 293(1): G91-103.

Kessova IG, Cederbaum AI. Mitochondrial alterations in livers of Sod1-/- mice fed alcohol. Free Radic Biol Med 2007 May 15; 42(10): 1470-1480.

Bai J, Cederbaum AI. Catalase protects HepG2 cells from apoptosis induced by DNA-damaging agents by accelerating the degradation of p53. J.Biol.Chem 2003; 278: 4660-4667.