Endocrinology and Metabolism Service
Department of Medicine
Hadassah University Hospital
Ein-Karem, Jerusalem
E-mail: danielle@md2.huji.ac.il
Phone: (+972)-2-677-8398
Fax: (+972)-2-643-7940
Senior Lecturer in Endocrinology
Endocrinology and Metabolism Service
Education
Ph.D. in the department of Cell Biology, the Weizmann Institute of Science, Rehovot, Israel.
1987 Postdoctoral fellow, in the department of Molecular Biology, Genentech Inc, South San Fransisco.
1988-90 Postdoctoral fellow, in the Hormone Research Institute, U.C.S.F., San Fransisco.
Employment
2000- Present: Senior Lecturer, Endocrinology and Metabolism
1994-1999 Lecturer, Endocrinology and Metabolism- Hadassah-Hebrew University Med. Ctr. Jerusalem
06/1990-93 Scientist, Lautenberg Center for Cancer and General Immunology. Hadassah Medical School, Jerusalem.
Areas of Research Interests
* Mechanisms of glucose-regulated insulin expression gene.
* Effect of hyperglycemia on beta-cell functions.ß
* Role of the Transcription Factor NF-B in beta-cells.
Membership in Professional Organizations
* The European Association for the Study of Diabetes
* The Israel Diabetes Association
* The Israel Endocrine Society
Research Projects
· Glucose effect on insulin gene expression. Characterization of the beta cell specific glucose sensitive factor (GSF/PDX-1). Mechanism of action.
· Control mechanisms involved in the tissue specific expression of the GSF/PDX-1 gene.
· Effect of chronic exposure of human islets to high glucose, on beta-cell functions.
· B in regulating beta-cell survival underkRole of the transcription factor NF- physiological and pathophysiological conditions.
Recent Representative Publications
· Melloul, D. Transcription Factors in Islet Development and Physiology: Role of PDX-1 in Beta-Cell Function. Ann N Y Acad Sci. 1014:28-37. 2004.
· Melloul D, Stoffel M. Regulation of transcriptional coactivator PGC-1alpha. Sci Ag Kn Env. 9: 9. Review. 2004.
· Schwitzgebel VM, Mamin A, Brun T, Ritz-Laser B, Zaiko M, Maret A, Jornayvaz FR, Theintz GE, Michielin O, Melloul D, Philippe J. Agenesis of human pancreas due to decreased half-life of insulin promoter factor 1. J Clin Endocrinol Metab. 88:4398-406. 2003.
· Melloul D., Tsur A, and D. Zangen. The ß-cell specific transcription factor PDX-1 in health and disease. Journal of Pediatric Endocrinology & Metabolism. 15:1461-72, 2002.
· Melloul D., Marshak S, and E. Cerasi. Regulation of insulin gene transcription. Diabetologia. 45:309-326, 2002.
· Melloul D, Marshak S, and E Cerasi. Regulated expression of the pdx-1 gene. Diabetes, 51 :S320-325. 2002.
· Leibowitz G, Yuli M, Donath YM, Melloul D, Cerasi E, Gross, JD and Kaiser, N. ß-Cell Glucotoxicity in the Psammomys obesus Model of Type 2. Diabetes. 50: S92- S96, 2001.
· Melloul, D. Glucose signaling to transcription factors of the insulin gene. In: Molecular Basis of Pancreatic Endocrine Development and Function. Eds. Habener J. F. & Hussain M. A. Kluwer Academic Publishers. Boston, pp 19- 33, 2001.
· Marshak S, Benshushan E, Shoshkes M, Leibovitz G, Kaiser N, Gross D, Bertuzzi F, Cerasi E and Melloul, D. ß- Cell- specific expression of the insulin and pdx-1 genes. Diabetes. 50: S110- 111, 2001.
· Marshak S, Benshushan E, Shoshkes M, Havin L, Cerasi, E and Melloul, D. Regulatory elements involved in human pdx-1 gene expression. Diabetes. 50: S33- S34, 2001.
· Leibowitz, G., Ferber, S., Apelqvist, A., Edlund, H., Gross, JD., Cerasi, E., Melloul, D. and Nurit Kaiser. ß-Cell dysfunction due to lack of functional Ipf1/Pdx1 in Psammomys obesus, an animal with Type 2 diabetes. Diabetes. 50:1799-806, 2001.
· BenShushan, E., Marshak., S, Shoshkes, M., Cerasi, E. and Melloul, D. A pancreatic aß-cell- specific enhancer in the human PDX-1 gene is regulated by HNF3ß, HNF1 and Sps transcription factors. J. Biol. Chem.276:17533-17540, 2001.
· Melloul, D., Kaiser, N. and E. Cerasi, Chronic Exposure to High Glucose Impairs Multiple ß-Cell Functions in Cultured Human Pancreatic Islets. Current Opinion in Endocrinology. 7: 44- 48, 2000.
· Marshak, S, Benshushan, E, Shoshkes, M, Havin, L, Cerasi, E and Melloul, D. Functional conservation of regulatory elements in the PDX-1 gene: PDX-1 and HNF3ß transcription factors mediate ß- cell specific expression. Mol. Cell. Biol. 20: 7583ñ7590, 2000.
· Ben-Shushan, E., Cerasi, E. and Melloul, D. Regulation of the insulin gene by glucose: Stimulation of transactivation potency of the human PDX-1 N-terminal domain. DNA Cell biology. 18: 471- 479, 1999.
· Marshak, S., Leibowitz, G, Socci, C., Bertuzzi, F., Kaiser, K., Gross, J. D., Cerasi, E and Melloul, D. Impaired ß-Cell functions induced by chronic exposure of cultured human pancreatic islets to high glucose. Diabetes. 48: 1230- 1236, 1999.
· Marshak, S., Totary, H., Cerasi, E. and Melloul, D. Purification of the ß-cell glucose-sensitive factor which transactivates the insulin gene differentially in normal and transformed islet cells. Proc. Natl. Acad. Sci. 93: 15057-15062, 1996.
· Melloul, D. and Cerasi, E. Transcription of the insulin gene: towards defining the glucose-sensitive cis-acting element and trans-acting factors. Diabetologia. S37: 3-10, 1994.
· Melloul, D., Ben-Neriah, Y. and Cerasi, E. Glucose modulates the binding of an islet specific factor to a conserved sequence within the rat I and the human insulin promoters. Proc. Natl. Acad. Sci. 90: 3865-3869, 1993.
· Eldor R., Yeffet A., Baum K., Doviner V., Amar D., Christofori G., Ben-Neriah Y. , Carel J.C. , Boitard C. , Klein T. , Serup P., Eizirik D.L. and D. Melloul. Conditional and specific NF-†B blockade protects pancreatic beta cells from diabetogenic inducers. Proc Natl Acad Sci U S A. 103:5072-5077. 2006.
· Neve B, Fernandez-Zapico ME, Ashkenazi-Katalan V, Dina C, Hamid YH, Joly E, Vaillant E, Benmezroua Y, Durand E, Bakaher N, Delannoy V, Vaxillaire M, Cook T, Dallinga-Thie GM, Jansen H, Charles MA, Clement K, Galan P, Hercberg S, Helbecque N, Charpentier G, Prentki M, Hansen T, Pedersen O, Urrutia R, Melloul D, Froguel P. Role of transcription factor KLF11 and its diabetes-associated gene variants in pancreatic beta cell function. Proc Natl Acad Sci U S A. 102:4807-12. 2005.
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