Research / Clinical
Summary
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Fred Levine, MD, PhD
Adjunct Professor, Pediatrics / The Burnham Institute for Medical Research
Cancer Biology Program
Contact by Email
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Diseases/Research Topics
Beta Cell, Cancer, Cell Line, Diabetes, Gene Therapy, Insulinoma, Oncogenes, Pancreas, Senescence, Transplantation
The major focus of Dr. Levine's 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, they 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 they have developed have extended lifespans, they are not truly immortal. Because of this, Levine and his associates 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 they 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, they have begun to focus on methods to induce hormone expression. By transferring b-cell-specific transcription factors into the cell lines, they have succeeded in upregulating the level of islet hormones, including somatostatin, and most significantly, insulin.
More recently, they 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.
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