UCLA - Division of Pulmonary & Critical Care Medicine

Elizabeta Nemeth, Ph.D.
Associate Professor of Medicine
Address: UCLA, Department of Medicine, CHS 52-239 10833 Le Conte Ave. Los Angeles, CA 90095-1690	Phone: Office: 310-825-7499 FAX: 310-206-8766 Email: enemeth@mednet.ucla.edu

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Education and Training:

Ph.D., Cell, Molecular and Neurosciences, University of Hawaii, 1998
B.S., Molecular Biology and Physiology, University of Belgrade, 1993

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Research Interests :

My research is focused on iron metabolism and its disorders. Iron is an essential trace element whose levels must be maintained in an optimal range. Iron deficiency causes cellular dysfunction most frequently manifested by anemia. Iron excess due to genetic causes or blood transfusion causes free radical mediated cell injury and carcinogenesis, manifested as hepatic cirrhosis, heart failure, multiendocrine failure, arthritis and hepatocellular carcinoma.
The master regulator of systemic iron metabolism is the peptide hormone hepcidin. We and others showed that hepcidin functions by inhibiting iron flows into plasma, including the absorption of dietary iron in the intestine, recycling of iron from old erythrocytes by macrophages, mobilization of iron from hepatic stores, and transfer of iron across the placenta. Hepcidin synthesis is homeostatically increased by plasma iron and iron stores, and decreased by erythropoietic activity, thus allowing modulation of iron absorption and recycling according to the body iron needs. At the molecular level, hepcidin acts by inducing degradation of its receptor, the iron channel ferroportin.
We also demonstrated hepcidin’s role as a pathogenic factor in iron disorders. Hepcidin deficiency or the resistance of ferroportin to hepcidin is the cause of all forms of hereditary hemochromatosis. Hepcidin deficiency also contributes to iron overload in patients with hereditary anemias such as beta-thalassemias. In contrast, elevated hepcidin during inflammation and infections contributes to the development of anemia of inflammation by causing iron retention in macrophages and blocking dietary iron absorption. Hepcidin thus may be useful target for improved diagnostics and therapy of iron disorders.

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Areas of Interest :

Mechanism of hepcidin dysregulation in iron overload diseases and inflammatory disorders
Molecular mechanism of hepcidin interaction with ferroportin
Development of hepcidin antagonists and agonist

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Representative Publications:

1. Nemeth E, Valore EV, Territo M, Schiller G, Lichtenstein A and Ganz T: Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein. Blood;101:2461-3, 2003.

2. Papanikolaou G, Samuels ME, Ludwig EH, MacDonald ML, Franchini PL, Dube MP, Andres L, MacFarlane J, Sakellaropoulos N, Politou M, Nemeth E, Thompson J, Risler JK, Zaborowska C, Babakaiff R, Radomski CC, Pape TD, Davidas O, Christakis J, Brissot P, Lockitch G, Ganz T, Hayden MR, Goldberg YP. Mutations in HFE2 cause iron overload in chromosome 1q-linked juvenile hemochromatosis. Nat Genet. 36:77-82, 2004.

3. Nemeth E, Rivera S, Gabayan V, Keller C, Taudorf S, Pedersen BK and Ganz T. Interleukin-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron-regulatory hormone hepcidin. J Clin Invest. 113:1271-1276, 2004.

4. Nemeth E, Roetto A, Garozzo G, Ganz T, Camaschella C. Hepcidin is decreased in TFR2-Hemochromatosis. Blood. 2005 Feb 15;105(4):1803-6.

5. Nemeth E. Ferroportin mutations: a tale of two phenotypes. Blood. 2005 May 15; 105: 3763-3764.

6. Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM, Ganz T, Kaplan J. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science. 306:2090-3, 2004.

7. Rivera S, Nemeth E, Gabayan V, Lopez MA, Farshidi D, Ganz T. Synthetic hepcidin causes rapid dose-dependent hypoferremia and is concentrated in ferroportin-containing organs. Blood. Sep 15;106(6):2196-9

8. Nemeth E, Preza GC, Jung CL, Kaplan J, Waring AJ, Ganz T. The N-terminus of hepcidin is essential for its interaction with ferroportin: structure-function study. Blood. 2006 Jan 1;107(1):328-33.

9. Ganz T and Nemeth E. Hepcidin and Regulation of Body Iron Metabolism. Review. Am J Physiol - GI and Liver Physiology. Feb 2006; 290: G199 - G203.

10. Nemeth E and Ganz T. Hepcidin and iron-loading anemias. Review. Haematologica. 2006 Jun;91(6):727-32.

11. Ganz T and Nemeth E. Regulation of iron acquisition and iron distribution in mammals. Review. Biochim Biophys Acta. 2006 Jul;1763(7):690-9.

12. Nemeth E and Ganz T. Regulation of iron metabolism by hepcidin. Review. Annu Rev Nutr. 2006;26:323-42.

13. Origa R, Galanello R, Ganz T, Giagu N, Maccioni L, Faa G, Nemeth E. Liver iron concentrations and urinary hepcidin in ß-thalassemia. Haematologica. 2007 May; 92(05):585-590.

14. Lin L, Valore E, Nemeth E, Goodnough J, Gabayan V, Ganz T. Iron-transferrin regulates hepcidin synthesis in primary hepatocyte culture through hemojuvelin and BMP2/4. Blood. 2007 Sep 15;110(6):2182-9.

15. Piperno A, Girelli D, Nemeth E, Trombini P, Bozzini C, Poggiali E, Phung Y, Ganz T, and Camaschella C. Blunted hepcidin response to oral iron challenge in HFE-hemochromatosis. Blood. 2007 Dec 1;110(12):4096-100.

16. Ganz T, Olbina G, Girelli D, Nemeth E and Westerman M. Immunoassay for Human Serum Hepcidin. Blood, 2008 Aug 8.

17. Nemeth E and Ganz T. Iron and aging. Blood Disorders in the Elderly. Balducci et al editors. Cambridge University Press 2008.

18. Nemeth E. Iron regulation and erythropoiesis. Current Opinions in Hematology 2008 May;15(3):169-75.

19. Fernandes A, Preza G, De Domenico I, Ganz T and Nemeth E. The molecular basis of hepcidin-resistant hereditary hemochromatosis. Blood. 2009 Jul 9;114(2):437-43.

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University of California at Los Angeles