Updated February 2008
Professor, Researcher,
Goldyne Savad Institute of Gene Therapy
Email: stella@cc.huji.ac.il
Affiliation
Hadassah University Hospital, the Hebrew University-Hadassah Medical School, Jerusalem, Israel
Education
1967-1970 B.Sc. in Biology at the University of Barcelona, Spain
1971-1973 M.Sc. in Microbiology, the Hebrew University of Jerusalem, Jerusalem, Israel.
1977-1981 Ph.D. in Virology, the Hebrew University of Jerusalem, Jerusalem, Israel. Advisors: Prof. N. Goldblum, Department of Virology, the Hebrew University of Jerusalem, Jerusalem; Prof. George Klein, Karolinska Institute, Stockholm, Sweden.
Research interests
Basic Research on Molecular Genetics mostly focused on muscular diseases
Selected Recent Publications
Eisenberg I, Eran A, Nishino I, Moggio M, Lamperti C, Amato AA, Lidov HG, Kang PB, North KN, Mitrani-Rosenbaum S, Flanigan KM, Neely LA, Whitney D, Beggs AH, Kohane IS, Kunkel LM. 2007. Distinctive patterns of microRNA expression in primary muscular disorders. Proc Natl Acad Sci USA. 104(43):17016-21.
Krause S, Aleo A, Hinderlich S, Merlini L, Tournev I, Walter MC, Argov Z, Mitrani-Rosenbaum S, Lochmuller H. 2007. GNE protein expression and subcellular distribution are unaltered in HIBM. Neurology 69(7):655-9.
Amsili S, Shlomai Z, Levitzki R, Krause S, Lochmuller H, Ben-Bassat H, Mitrani-Rosenbaum S. 2007. Characterization of hereditary inclusion body myopathy myoblasts: possible primary impairment of apoptotic events. Cell Death Differ 14(11):1916-24.
Nissan A, Jager D, Roystacher M, Prus D, Peretz T, Eisenberg I, Freund HR, Scanlan M, Ritter G, Old LJ, Mitrani-Rosenbaum S. 2006. Multimarker RT-PCR assay for the detection of minimal residual disease in sentinel lymph nodes of breast cancer patients. Br J Cancer 94(5):681-5.
Penner J, Mantey LR, Elgavish S, Ghaderi D, Cirak S, Berger M, Krause S, Lucka L, Voit T, Mitrani-Rosenbaum S, Hinderlich S. 2006. Influence of UDP-GlcNAc 2-epimerase/ManNAc kinase mutant proteins on hereditary inclusion body myopathy. Biochemistry 7;45(9):2968-77.
Krause S, Hinerlich S, Amsili S, Horstkorte R, Wiendl H, Argov Z, Mitrani-Rosenbaum S, Lochmuller H. 2005. Localization of UDP-G1cNAc 2-epimerase/ManAc kinase (GNE) in the Gilgi complex and the nucleus of mammalian cells. Exp Cell Res 304:365-379.
Salama I, Hinderlich S, Shlomai Z, Eisenberg I, Krause S, Yarema K, Argov Z, Lochmuller H, Reutter W, Dabby R, Sadeh M, Ben-Bassat H, Mitrani-Rosenbaum S. 2005. No overall hyposialylation in hereditary inclusion body myopathy myoblasts carrying the homozygous M712T GNE mutation. Biochem Biophys Res Commun 328(1):221-6.
Avidor B, Efrat G, Weinberg M, KraOz Z, Satinger J, Mitrani-Rosenbaum S, Yaron Y, Shulman L, Tepperberg-Oikawa M, Wolf D, Berger SA, Lipitz S, Mendelson E, Giladi M. 2004. Insight into the intrinsic sensitivity of the PCR assay used to detect CMV infection in amniotic fluid specimens. J Clin Virol 4:260-70.
Hinderlich S, Salama I, Eisenberg I, Potikha T, Mantey L, Yarema K, Horstkorte R, Argov Z, Sadeh M, Reutter W, Mitrani-Rosenbaum S. 2004. The homozygous M712T mutation of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase results in reduced enzyme activities but not in altered cellular sialylation in hereditary inclusion body myopathy. FEBS Letters 566:105-109.
Eisenberg I., Grabov-Nardini G., Hochner H., Korner M., Sadeh M., Bertorini T., Bushby K., Castellan C., Felice K., Mendell J., Merlini M., Shilling C., Wirguin I., Argov Z., Mitrani-Rosenbaum S. 2003. Mutations spectrum of the GNE gene in Hereditary Inclusion Body Myopathy sparing the quadriceps. Hum Mutat 21: 99.
Argov Z., Eisenberg I., Grabov-Nardini G., Sadeh M.,Wirguin I., Soffer D., Mitrani-Rosenbaum S. 2003. Hereditary Inclusion Body Myopathy: the middle eastern genetic cluster. Neurology 60:1519-1523.
Hinderlich S., Salama I., Eisenberg I., Mitrani-Rosenbaum, S. 2003. Distal myopathy with rimmed vacuoles is allelic to hereditary inclusion body myopathy". Neurology 61:145.
Eisenberg I., Barash M., Kahan T., Mitrani-Rosenbaum S. 2002. Cloning and characterization of a human novel gene C9orf19 encoding a conserved putative protein with an SCP-like extracellular protein domain. Gene 293:141-8
Eisenberg 2002. Cloning and characterization of a novel human gene RNF38 encoding a conserved putative protein with a RING finger domain. Biochem Biophys Res Commun 294:1169-76 I., Hochner H., Levi T., Yelin R., Kahan T.(C), Mitrani-Rosenbaum S.
Eisenberg I., Hochner H., Sadeh M., Argov Z., Mitrani Rosenbaum S. 2002. Establishment of the genomic structure and identification of thirteen single-nucleotide polymorphisms in the human RECK gene. Cytogenet Genome Res 97:58-61.
Research group
Post doc:
Iris Eisenberg, Ph.D., tel 44727,email: eisenb@md.huji.ac.il
Ph.D. students:
Ilan Salama, tel 44701, salami@pob.huji.ac.il
Shira Amsili, tel 44700, shir1@md.huji.ac.il
M.Sc students:
Adi Rizansky, tel 44702, adirizansky@md.huji.ac.il
Yulia Luktav, tel 44702, yuliag@md.huji.ac.il
Michal Becker-Cohen, tel 44716, michalbec@md.huji.ac.il
Collaborators
Prof Werner Reutter, Dr Stephan Hinderlich, Institut für Biochemie und Molekularbiologie, Charité Universitätsmedizin, Berlin
Dr Kevin Yarema, Whitaker Institute of Biomedical Engineering The Johns Hopkins University, Baltimore
Prof Hanns Lochmuller, Genzentrum and Friedrich-Baur-Institute, Ludwig-Maximilians-University, Munich
Prof Zohar Argov, Hadassah University Hospital
Prof Menachem Sadeh, Wolfson Hospital
Prof Hannah Ben-Bassat
Dr.Aviram Nissan, Hadassah University Hospital
Prof Chani Maayan, Hadassah University Hospital
Dr Ronen Segman, Hadassah University Hospital
Dr Annick Raas Rothschild, Hadassah University Hospital
Dr Azaria Rein, Hadassah University Hospital
Dr Stanley Kurman, Hadassah University Hospital
RESEARCH SUMMARY
Hereditary Inclusion Body Myopathy: Characterization of the effects of the mutated GNE gene in the pathophysiology of muscle tissue.
Hereditary Inclusion Body Myopathy (HIBM) is a unique group of neuromuscular disorders characterized by adult-onset, slowly progressive distal and proximal muscle weakness, and typical muscle pathology, including rimmed vacuoles and filamentous inclusions. This disease is the most common form of ethnic-related familial degenerative myopathy, with a prevalence of 1:1500 in the Jewish Iranian community. The identification in our laboratory of GNE as the gene causing HIBM, a form of myopathy till then considered almost exclusively as a Middle Eastern Jewish disease, allowed the recognition of that same disorder worldwide and a new classification of this group of diseases.
UDP-N-acetylglucosamine2-epimerase/ N-acetylmannosamine kinase (GNE) is a bifunctional enzyme which plays a key role in the biosynthetic pathway of sialic acid. Because of its terminal position on macromolecules and on cell membranes, sialic acid is an essential molecule involved in many biological and pathological processes.
Our research is now aimed towards the understanding of the biochemistry and biology of GNE in non affected muscle, and subsequently in HIBM muscle tissue, by investigating different biochemical and biological aspects of the GNE activity in muscle tissue and cell cultures. Transgenic animals will also be established bearing the mutated gene. Simultaneously we are investigating the potential partners of GNE in muscle cells by mass spectrometry, and microchip technology.
We anticipate that these in vitro and in vivo systems specifically designed for a genomic and proteomic approach will provide us with the necessary tools to unravel the mechanisms of GNE protein in normal muscle tissue and possible steps for the eventual correction of the mutation effect in HIBM.
Identification of genes involved in hereditary cardiomyopathies
Recently, several transcription factors have been implicated in the complex biological process of cardiac development. An approach to the understanding of some of the steps involved is the identification of human mutations that cause congenital heart disease. In collaboration with Dr Annick Raas Rothschild from the Department of Human Genetics and Dr Azaria Rein from the Department of Pediatric Cardiology, we are analyzing various families affected by congenital cardiac diseases.
Molecular markers for the detection of breast and colon cancer micrometastases in axillary lymph nodes
Micrometastases in axillary lymph nodes have been detected by serial sectioning and immunohistochemistry., and shown to have prognostic significance. When compared to node-negative disease, the presence of even a single micrometastasis in a lymph node, is associated with a significant difference in recurrence and survival, and therefore will determine the nature of the treatment to follow. In collaboration with Dr Aviram Nissan, from the Department of Surgery at Mount Scopus, we are developing assays for an increased rate of detection of tumor involvement within an excised node, by the measurement of differentially expressed gene transcripts, using a Real Time PCR amplification methods.