Fred Levine - Investigator Profile
The major focus of my laboratory is on the relationship between growth and differentiation of the human endocrine pancreas. The ultimate goal of this work is to develop expanded populations of human pancreatic b-cells that might be used for b-cell replacement. To this end, we have been using retroviral vectors expressing dominant oncogenes under inducible control to develop cell lines from the endocrine cells and endocrine precursor cells of the human adult and fetal pancreas. Although the cell lines that we have developed have extended lifespans, they are not truly immortal. Because of this, we have initiated studies to examine the role of telomere length and telomerase in immortalization of both primary pancreatic endocrine cells as well as the cell lines. The cell lines that we have developed express islet hormones, but only at low levels. Because of the loss of hormone expression in the primary cells and the cell lines, we have begun to focus on methods to induce hormone expression. By transferring b-cell-specific transcription factors into the cell lines, we have succeeded in upregulating the level of islet hormones, including somatostatin, and most significantly, insulin. More recently, we have succeeded in recapitulating the entire b-cell differentiation program in vitro. These studies should lead to a more complete understanding of the relationship between cellular growth and differentiation in the pancreas.
Scientific Interests/Keywords
Gene Therapy, Gene Transfer, Diabetes, Retroviral Vectors, Oncogenes, Islet Cell
Publications
| Publication | Citation |
|---|---|
| 12107268 | Demeterco C, Itkin-Ansari P, Tyrberg B, Ford LP, Jarvis RA, Levine F c-Myc controls proliferation versus differentiation in human pancreatic (2002) J Clin Endocrinol Metab 87: 3475-85 (Added 2005-04-13 12:55:58) |
| 12003641 | Tyrberg B, Anachkov KA, Dib SA, Wang-Rodriguez J, Yoon KH, Levine F Islet expression of the DNA repair enzyme 8-oxoguanosine DNA glycosylase (2002) BMC Endocr Disord 2: 2 (Added 2005-04-13 12:55:56) |
| 11899076 | Halvorsen T, Levine F Diabetes mellitus-cell transplantation and gene therapy approaches. (2001) Curr Mol Med 1: 273-86 (Added 2005-04-13 12:55:46) |
| 11846472 | Gordon SL, Oppenheimer SR, Mackay AM, Brunnabend J, Puhlev I, Levine F Recovery of human mesenchymal stem cells following dehydration and (2001) Cryobiology 43: 182-7 (Added 2005-04-13 12:55:51) |
| 11846465 | Lao G, Polayes D, Xia JL, Bloom FR, Levine F, Mansbridge J Overexpression of trehalose synthase and accumulation of intracellular (2001) Cryobiology 43: 106-13 (Added 2005-04-13 12:55:53) |
| 11763159 | Tyrberg B, Levine F Current and future treatment strategies for type 2 diabetes: the beta-cell (2001) Curr Opin Investig Drugs 2: 1568-74 (Added 2005-04-13 12:55:48) |
| 11578120 | Puhlev I, Guo N, Brown DR, Levine F Desiccation tolerance in human cells. (2001) Cryobiology 42: 207-17 (Added 2005-04-13 13:07:18) |
| 11313956 | Wood LD, Halvorsen TL, Dhar S, Baur JA, Pandita RK, Wright WE, Hande MP, Calaf G, Hei TK, Levine F, Shay JW, Wang JJ, Pandita TK Characterization of ataxia telangiectasia fibroblasts with extended (2001) Oncogene 20: 278-88 (Added 2005-04-13 13:07:21) |
| 11222748 | de la Tour D, Halvorsen T, Demeterco C, Tyrberg B, Itkin-Ansari P, Loy M, Yoo SJ, Hao E, Bossie S, Levine F Beta-cell differentiation from a human pancreatic cell line in vitro and (2001) Mol Endocrinol 15: 476-83 (Added 2005-04-13 12:55:43) |
| 11171547 | Demeterco C, Levine F Gene therapy for diabetes. (2001) Front Biosci 6: D175-91 (Added 2005-04-13 12:55:41) |
