Fred Levine, M.D., Ph.D.[La Jolla]
As a Pediatric Geneticist who takes care of children with inherited metabolic diseases, I have always been interested in understanding and developing new therapies for childhood diseases. Sanford-Burnham offers an incredibly rich environment in which that goal can be achieved.
Dr. Levine studies the process of pancreatic beta-cell regeneration, with the goal of developing new therapies for diabetes.
Dr. Levine received his M.D. and Ph.D. degree in genetics from the University of Washington.
View All Publications
Induction of β-cell replication by a synthetic HNF4α antagonist.
Lee SH, Piran R, Keinan E, Pinkerton A, Levine F
Stem Cells. 2013 Nov;31(11):2396-407
HNF4α antagonists discovered by a high-throughput screen for modulators of the human insulin promoter.
Kiselyuk A, Lee SH, Farber-Katz S, Zhang M, Athavankar S, Cohen T, Pinkerton AB, Ye M, Bushway P, Richardson AD, Hostetler HA, Rodriguez-Lee M, Huang L, Spangler B, Smith L, Higginbotham J, Cashman J, Freeze H, Itkin-Ansari P, Dawson MI, Schroeder F, Cang Y, Mercola M, Levine F
Chem Biol. 2012 Jul 27;19(7):806-18
Id3 upregulates BrdU incorporation associated with a DNA damage response, not replication, in human pancreatic β-cells.
Lee SH, Hao E, Levine F, Itkin-Ansari P
Islets. 2011 Nov-Dec;3(6):358-66
The Id3/E47 axis mediates cell-cycle control in human pancreatic ducts and adenocarcinoma.
Lee SH, Hao E, Kiselyuk A, Shapiro J, Shields DJ, Lowy A, Levine F, Itkin-Ansari P
Mol Cancer Res. 2011 Jun;9(6):782-90
CENP-A, a protein required for chromosome segregation in mitosis, declines with age in islet but not exocrine cells.
Lee SH, Itkin-Ansari P, Levine F
Aging (Albany NY). 2010 Nov;2(11):785-90
Adult pancreatic alpha-cells: a new source of cells for beta-cell regeneration.
Chung CH, Levine F
Rev Diabet Stud. 2010;7(2):124-31
Pancreatic β-cell neogenesis by direct conversion from mature α-cells.
Chung CH, Hao E, Piran R, Keinan E, Levine F
Stem Cells. 2010 Sep;28(9):1630-8
Phenothiazine neuroleptics signal to the human insulin promoter as revealed by a novel high-throughput screen.
Kiselyuk A, Farber-Katz S, Cohen T, Lee SH, Geron I, Azimi B, Heynen-Genel S, Singer O, Price J, Mercola M, Itkin-Ansari P, Levine F
J Biomol Screen. 2010 Jul;15(6):663-70
Islet specific Wnt activation in human type II diabetes.
Lee SH, Demeterco C, Geron I, Abrahamsson A, Levine F, Itkin-Ansari P
Exp Diabetes Res. 2008;2008:728763
Beta-cell differentiation from nonendocrine epithelial cells of the adult human pancreas.
Hao E, Tyrberg B, Itkin-Ansari P, Lakey JR, Geron I, Monosov EZ, Barcova M, Mercola M, Levine F
Nat Med. 2006 Mar;12(3):310-6
c-Myc controls proliferation versus differentiation in human pancreatic endocrine cells.
Demeterco C, Itkin-Ansari P, Tyrberg B, Ford LP, Jarvis RA, Levine F
J Clin Endocrinol Metab. 2002 Jul;87(7):3475-85
Accelerated telomere shortening and senescence in human pancreatic islet cells stimulated to divide in vitro.
Halvorsen TL, Beattie GM, Lopez AD, Hayek A, Levine F
J Endocrinol. 2000 Jul;166(1):103-9
Telomerase activity is sufficient to allow transformed cells to escape from crisis.
Halvorsen TL, Leibowitz G, Levine F
Mol Cell Biol. 1999 Mar;19(3):1864-70
Fred Levine's Research Focus
Obesity, Type 1 Diabetes, Type 2 Diabetes, Childhood Diseases, Metabolic Diseases, Cancer
Watch Dr. Levine describe his research
Diabetes is a disease in which there is an insufficient amount of insulin, produced by the pancreatic b-cells, to control the blood glucose concentration. In type I diabetes, the b-cell are destroyed by an autoimmune response, while in type II diabetes, the b-cells are dysfunctional and are ultimately lost because of obesity-associated pathology. Our laboratory is interested in how b-cells regenerate under normal and pathophysiological conditions, with the goal of developing new therapies for diabetes that result in an increased number of those cells. Our studies of b-cell growth have also led us to develop lead compounds that are active in cancer, an interesting connection as both obesity and diabetes are now recognized as major risk factors for cancer.
Fred Levine's Research Report
The major interest in the laboratory is pancreatic beta-cell biology and specifically the control of beta-cell growth and differentiation in the adult pancreas. In both type I and type II diabetes,
β-cell mass decreases and is a major factor in the pathogenesis of diabetes. Thus, one major question in which we are interested is the existence and nature of adult endocrine stem/progenitor cells. Using both human and rodent models, we study cells
in vitro and in vivo to determine the competence of various cell populations to undergo endocrine differentiation in response to defined stimuli. The goal is to achieve a sufficient understanding of the process of adult
β-cell regeneration to allow us to enhance
β-cell mass in diabetes.
A second major area of emphasis is to use high-throughput screening to discover compounds that modulate important aspects of
β-cell biology. Our focus has been on modulation of insulin promoter activity, as that gene is acted upon by many diabetogenic stimuli. We have isolated and are characterizing a number of compounds and genes that were discovered in the screening process. Recently, we have discovered ligands for the orphan nuclear receptor HNF4a. HNF4a is involved in a number of diseases processes, including diabetes, liver disease, and cancer.
About Fred Levine
Dr. Levine is a Professor and Director of the Sanford Children’s Health Research Center at Sanford-Burnham Medical Research Institute. Prior to that, he was a Professor in the Department of Pediatrics at the University of California, San Diego School of Medicine, where he continues to see children with inherited metabolic diseases. Dr. Levine received his undergraduate degree in biochemistry from Harvard and his M.D. and Ph.D. degree in genetics from the University of Washington. His clinical training as a pediatric geneticist was at the Children’s Hospital of Philadelphia. Dr. Levine has been working in the field of cell transplantation therapies for diabetes and b-cell biology for more than fifteen years. His laboratory was the first to develop immortalized cell lines from the human endocrine pancreas as models of beta-cell growth and differentiation. He has made insights into cellular senescence in the endocrine pancreas, finding that b-cells undergo rapid senescence when stimulated to proliferate. Most recently, he and his co-workers demonstrated the existence of endocrine stem cells in the adult human pancreas. The laboratory continues to pursue the development of cell therapies for diabetes using a variety of approaches, including high throughput screening.
1975-79 A.B. Harvard University (Biochemistry)
1979-86 M.D. University of Washington
1979-86 Ph.D. University of Washington (Genetics)
1986-87 Pediatric Intern, Children's Hosp. of Philadelphia
1987-89 Pediatric Resident, Children's Hosp. of Philadelphia
1988-89 Clinical Genetics Fellow, Children's Hosp. of Philadelphia
1989-91 Genetics Fellow, Dept. of Pediatrics, UCSD School of Medicine
Health Sciences Clinical Professor of Pediatrics, UCSD School of Medicine
Attending Physician, Rady Children's Hospital