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Arthur 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

Biography

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

Research

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

Wu D, Cederbaum AI. Inhibition of autophagy promotes CYP2E1-dependent toxicity in HepG2 cells via elevated oxidative stress, mitochondria dysfunction and activation of p38 and JNK MAPK. Redox Biology 2013 Nov; 1(1): 552-65.

Lu Y, Ward SC, Cederbaum AI. Nicotine enhances ethanol-induced fat accumulation and collagen deposition but not inflammation in mouse liver. Alcohol 2013 Aug; 47(5): 353-7.

Wang X, Wu D, Yang L, Gan L, Cederbaum AI. Cytochrome P450 2E1 potentiates ethanol induction of hypoxia and HIF-1α in vivo. Free Radical Biology and Medicine 2013 Oct; 63: 175-86.

Cederbaum AI. Nrf2 and Antioxidant Defense Against CYP2E1 Toxicity. Sub-cellular Biochemistry 2013; 67: 105-30.

Wu D, Wang X, Zhou R, Yang L, Cederbaum AI. Alcohol steatosis and cytotoxicity: the role of cytochrome P4502E1 and autophagy. Free Radical Biology and Medicine 2012 Sep; 53(6): 1346-57.

Yang L, Wu D, Wang X, Cederbaum AI. Cytochrome P4502E1, oxidative stress, JNK, and autophagy in acute alcohol-induced fatty liver. Free Radical Biology and Medicine 2012 Sep; 53(5): 1170-80.

Lu Y, Zhang XH, Cederbaum AI. Ethanol induction of CYP2A5: role of CYP2E1-ROS-Nrf2 pathway. Toxicological Sciences 2012 Aug; 128(2): 427-38.

Cederbaum AI, Yang L, Wang X, Wu D. CYP2E1 Sensitizes the Liver to LPS- and TNF α-Induced Toxicity via Elevated Oxidative and Nitrosative Stress and Activation of ASK-1 and JNK Mitogen-Activated Kinases. International Journal of Hepatology 2012; 2012.

Yang L, Wu D, Wang X, Cederbaum AI. Depletion of cytosolic or mitochondrial thioredoxin increases CYP2E1-induced oxidative stress via an ASK-1-JNK1 pathway in HepG2 cells. Free Radical Biology and Medicine 2011 Jul; 51(1): 185-96.

Lu Y, Wu D, Wang X, Ward SC, Cederbaum AI. Ethanol induction of CYP2A5: permissive role for CYP2E1. Drug Metabolism and Disposition 2011 Feb; 39(2): 330-6.

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 2013 and/or 2014: 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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1468 Madison Avenue
New York, NY 10029

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

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

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