faculty photo

Itzhak Nissim

Research Professor of Pediatrics
Department: Pediatrics

Contact information
CHOP, Division of Metabolism and Genetic
34th & CIVIC CENTER 4399
Philadelphia, PA 19104
Office: 2155903392
Fax: 2155905199
Education:
B.Sc. (Life Science)
Bar Ilan University, Ramat Gan, Israel , 1972.
M.Sc. (Life Science)
Hebrew University, Jerusalem, Israel, 1974.
Ph.D. (Life Science)
Weizmann Institute of Science, Rehovot, Israel, 1979.
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Description of Research Expertise

I am a biochemist with a long-standing interest in research related to metabolic disorders, including neurochemical aberrations, defects in hepatic nitrogen metabolism, obesity, fatty liver disease, diabetes and pathogenic mitochondrial integrity and function. A special emphasis is on development of pharmacotherapeutic intervention to mitigate metabolic derangements. I have pursued studies to understand the benefits and risks of drugs for treatment of obesity-induced metabolic derangements, impaired hepatic nitrogen metabolism, type-2-diabetes, the regulation of insulin release from β-cells, the benefits of ketogenic diet in cases of neurochemical aberrations or amino acids diet in case of traumatic brain injury.

Description of Other Expertise

As a director of the Metabolomic Core Facility at Children’s Hospital of Philadelphia, I have collaborated and contributed to many projects investigating metabolomic profiling in normal and disease states such as, neurological dysfunction caused by traumatic brain injury, the molecular and metabolomic profiling in animal models of cancer before and after chemotherapy treatment, the molecular and metabolomic characteristic of renal carcinoma or the mTOR and protein homeostasis. As a member of the Institute of Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, I have been involved in various projects dealing with hepatic metabolism and insulin resistance, obesity or diabetes. My research is unique in its use of in vivo and in vitro model systems, and methodological approach including, molecular biology, stable isotopes, liquid chromatography-mass spectrometry and Nuclear Magnetic Resonance to determine body composition, metabolic fluxes and metabolomic profiling.

Selected Publications

Bo Li, Bo Qiu, David S.M. Lee, Zandra E. Walton, Joshua D. Ochocki, Lijoy K. Mathew, Anthony Mancuso, Terence P.F. Gade, Brian Keith, Itzhak Nissim, and M. Celeste Simon: Fructose-1,6-bisphosphatase opposes renal carcinoma progression. Nature September 12 2014 Notes: In Press.

Nissim I, Horyn O, Daikhin Y, Li C, Chen P, Wherli Z. Nissim Ilana and Yudkoff M: The Molecular and Metabolic Influence of Long Term Agmatine Consumption. J Biol Chem. 289(14): 9710-9729, 04 2014.

Li C, Liu C, Nissim I, Chen J, Chen P, Doliba N, Zhang T, Nissim I, Daikhin Y, Stokes D, Yudkoff M, Bennett MJ, Stanley CA, Matschinsky FM, Naji A.: Regulation of glucagon secretion in normal and diabetic human islets by γ-hydroxybutyrate and glycine. J. Biol. Chem. 288(3): 3938-3951, 2013.

Cang C, Zhou Y, Navarro B, Seo YJ, Aranda K, Shi L, Battaglia-Hsu S, Nissim I, Clapham DE, Ren D.: mTOR regulates lysosomal ATP-sensitive two-pore Na(+) channels to adapt to metabolic state. Cell 152(4): 778-790, 2013.

Nissim I, Horyn O, Ilana Nissim, Daikhin Y, Wehrl SL,Yudkoff M and Matschinsky FM: : Effects of a glucokinase activator onhepatic intermediary metabolism: study with 13C-isotopomer-based metabolomics. Biochem J. 444: 537-551, 2012.

Changhong Li, Chengyang Liu, Itzhak Nissim , et al.: : Regulation of Glucagon Secretion in Normal and Diabetic Human Islets by Gamma-Hydroxybutyrate and Glycine. J Biol Chem, 2012.

Falk MJ, Polyak E, Zhang Z, Peng M, King R, Maltzman JS, Okwuego E, Horyn O, Nakamaru-Ogiso E, Ostrovsky J, Xie LX, Chen JY, Marbois B, Nissim I, Clarke CF, Gasser DL: Probucol ameliorates renal and metabolic sequelae of primary CoQ deficiency in Pdss2 mutant mice. EMBO Mol Med. 7: 410-427, 2011.

Nissim I, Horyn O, Nissim I, Daikhin Y, Caldovic L, Barcelona B, Cervera J, Tuchman M,Yudkoff M.: Down-regulation of hepatic urea synthesis by oxypurines: xanthine and uric acid inhibit N-acetylglutamate synthase. J Biol Chem. 286: 22055-22068, 2011.

Li C, Chen P, Palladino A, Narayan S, Russell LK, Sayed S, Xiong G, Chen J, Stokes D, Butt YM, Jones PM, Collins HW, Cohen NA, Cohen AS, Nissim I, Smith TJ, Strauss AW, Matschinsky FM, Bennett MJ, Stanley CA. : Mechanism of hyperinsulinism in short-chain 3- hydroxyacyl-CoA dehydrogenase deficiency involves activation of glutamate dehydrogenase. J Biol Chem. 285: 1806-1818, 2010.

Nissim I, , Horyn O, Daikhin Y, Nissim I, Luhovyy B., Phillips, PC, and Yudkoff M.: Ifosfamide-Induced Nephrotoxicity: Mechanism and Prevention Cancer Res. 66 66: 7824-7831, 2006.

Yudkoff M, Ah Mew N, Daikhin Y, Horyn O, Nissim I, Nissim I, Payan I, Tuchman M. : Measuring in vivo ureagenesis with stable isotopes. Mol Genet Metab. 100: 37-41, 2010.

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Last updated: 11/03/2014
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