Photo of Arthur I. Cederbaum

Arthur I. Cederbaum

  • PROFESSOR Pharmacology and Systems Therapeutics
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Education

  • Fellowship, Princeton University

  • Ph.D., Rutgers University
    Biochemistry

  • Fellowship, Mount Sinai School of Medicine

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 - 1990, 1991, 1992, 1996, 1999, 2001, 2003
    Excellence in Teaching Medical School

  • 1990 - 1999
    MERIT AWARD
    NIH/NIAAA

Research

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

Postdoctoral Fellows: Aparajita Dey, Yongke Lu, Xiadong Wang, Lili Yang

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.

Publications

Lu Y, Wu D, Wang X, Ward SC, Cederbaum AI. Chronic alcohol-induced liver injury and oxidant stress are decreased in cytochrome P4502E1 knockout mice and restored in humanized cytochrome P4502E1 knock-in mice. Free Radic Biol Med 2010 Nov; 49(9): 1406-1416.

Cederbaum A. Nrf2 and antioxidant defense against CYP2E1 toxicity. Expert Opin Drug Metab Toxicol 2010 Oct; 5(10): 1223-1244.

Wu D, Cederbaum A. Activation of ASK-1 and downstream MAP kinases in cytochrome P4502E1 potentiated tumor necrosis factor alpha liver injury.. Free Radic Biol Med 2010 Aug; 49(3): 348-360.

Wang X, Lu Y, Xie B, Cederbaum AI. Chronic ethanol feeding potentiates Fas Jo2-induced hepatotoxicity: role of CYP2E1 and TNF-alpha and activation of JNK and P38 MAP kinase. Free Radic Biol Med 2009 Sep; 47(5): 518-528.

Wu D, Cederbaum AI. Oxidative stress and alcoholic liver disease. Semin Liver Dis 2009 May; 29(2): 141-154.

Wu D, Xu C, Cederbaum AI. Role of nitric oxide and nuclear factor-kappaB in the CYP2E1 potentiation of tumor necrosis factor alpha hepatotoxicity in mice. Free Radic Biol Med 2009 Feb; 46(4): 480-491.

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

Lu Y, Cederbaum AI. CYP2E1 and oxidative liver injury by alcohol. Free Radic Biol Med 2008 Mar ; 44(5): 723-738.

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

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 Jul; 293(1): G91-103.

Industry Relationships

Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device and biotechnology companies to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their relationships with such companies.

Dr. Cederbaum did not report having any of the following types of financial relationships with industry during 2012 and/or 2013: consulting, scientific advisory board, industry-sponsored lectures, service on Board of Directors, participation on industry-sponsored committees, equity ownership valued at greater than 5% of a publicly traded company or any value in a privately held company. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.

Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website at http://icahn.mssm.edu/about-us/services-and-resources/faculty-resources/handbooks-and-policies/faculty-handbook. Patients may wish to ask their physician about the activities they perform for companies.

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Address

Annenberg Building Floor 19 Room 19-14 (Lab)
1468 Madison Avenue
New York, NY 10029

Tel: 212-241-7285
Fax: 212-996-7214

Address

Annenberg Building Floor 19 Room 19-10 (Office)
1468 Madison Avenue
New York, NY 10029

Tel: 212-241-9352
Fax: 212-996-7214

Address

Annenberg Building Floor 19 Room 19-20 (Lab)
1468 Madison Avenue
New York, NY 10029

Tel: 212-241-7285
Fax: 212-996-7214