Last Updated: 5/13/2009

Clinical Interests
Pediatric Endocrinology

Research Interests
Our laboratory primarily focuses on the in vivo actions of insulin-like growth factor-I (IGF-I) in the central nervous system by generating transgenic mice with alterations in IGF-I expression or function in the brain. Our studies focus on IGF-I mechanisms of action in the brain and do not directly address a role for IGF-I in tumorigenesis. Nonetheless, this research has relevance to cancer because IGF-I has been implicated as a progression factor in the growth of a number of cancers, including those of the nervous system. Specifically, one aspect of our work investigates the role of IGF-I in the stimulation of neuron proliferation and the inhibition of neuron apoptosis, and asks whether IGF-I also increases neuron number by promoting their differentiation from neural stem cells. Our work has demonstrated that IGF-I can increase neuron number by stimulating proliferation of neuron progenitors in the embryo (by shorten the duration of G1 in the cell cycle) and by inhibiting apoptosis later in development. In other work, we study IGF-I's influence on cells in the oligodendrocyte lineage, and recently have focused on the mechanisms that govern oligodendrocyte development. We have shown that IGF-I is a potent stimulator of myelination, and that it protects oligodendrocytes from a variety of injuries, such as the demyelination induced by TNF-alpha and interferon-gamma.

Recent Accomplishments and Honors
We have demonstrated that IGF-I has potent effects on the survival of neuron and oligodendrocytes. In addition, we have made significant progress in delineating IGF-I signaling mechanisms in vivo. We also have shown that IGF-I can ameliorate the demyelinating effects of Tumor Necrosis Factor-alpha (TNF- alpha). Each of these finding suggest that IGF-I could be therapeutically valuable in the treatment of a variety of injuries to the CNS, including those that result from cancer treatment (e.g. radiation and chemotherapy).

Publications
Publications Publications in the last two years:

Ye P, Kollias G, and D'Ercole AJ.2007 Insulin-like Growth Factor (IGF)-I ameliorates demyelination induced by tumor necrosis factor in transgenic mice. J. Neurosci. Res. 85: 712-722.(TNF)-

Zeger M, Popken G, Zhang J, Xuan S, Lu QR, Schwab MH, Nave K-A, Rowitch D, D'Ercole AJ, and Ye P. 2007 Insulin-like growth factor type 1 receptor signaling in the cells of oligodendrocyte lineage is required for normal in vivo oligodendrocyte development and myelination. Glia 55(4): 400-411.

Lagarde WH, Benjamin R, Heerens AT, Ye P, Cohen RI, Moats-Staats B, and D'Ercole AJ. 2007. Non-transformed oligodendrocyte precursor cell Line, OL-1, facilitates studies of insulin-like growth factor-I (IGF-I) signaling during oligodendrocyte development. Internatl. J. Develop. Neurosci. 25: 95-105.

Zhang J, Moats-Staats B, Ye P and D'Ercole AJ. 2007. Expression of Insulin-like Growth Factor System Genes during the Early Postnatal Neurogenesis in the Mouse Hippocampus. J. Neurosci. Res. 85:1618-1627.

Hodge A, D'Ercole AJ, and O'Kusky, JR. 2007 Insulin-like Growth Factor I (IGF-I) inhibits neuronal apoptosis in the developing cerebral cortex in vivo. Internatl. J. Develop. Neurosci. 25:233-241.

Liu H, Hu Q, Kaufman A, D'Ercole AJ, and Ping Ye. 2008 Developmental expression of Histone Deacetylase 11 in Murine Brain. J Neurosci Res 86:537-543.

Coulter DW, Blatt J, D'Ercole AJ, and Moats-Staats. 2008 IGF-I Receptor Inhibition Combined with Rapamycin or Temsirolimus Inhibits Neuroblastoma Cell growth. Anticancer Res. 28:1509-1516.

Liu H, Hu Q, D'Ercole AJ, and Ping Ye. 2008 Histone Deacetylase 11 regulates oligodendrocyte gene expression and development. Glia 57:1-12

D'Ercole AJ and Ye P, 2008 Minireview: Expanding the Mind: IGF-I and Brain Development. Endocrinology. 149:5958-5962.

Liu W, Ye P, O'Kusky JR, and D'Ercole AJ. 2009. Type 1 Insulin-like growth factor receptor signaling is essential for essential for the development of the hippocampal formation and dentate gyrus. J. Neurosci. Res. (in press).

E-mail: ajd@med.unc.edu
Telephone: (919) 966-4435
FAX: (919) 966-2423
Address: Dept. of Pediatrics Chapel Hill, NC

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