DANIEL W. FULTS
Daniel W. Fults
email: daniel.fults@hsc.utah.edu		 Professor of Neurosurgery

Neurobiology of Disease

B.S. 1975, University of Texas-Austin; M.D. 1979, University of Texas Southwestern; Post-graduate training in neurosurgery, 1979-1985, Wake Forest University School of Medicine; Postdoctoral Fellow, 1985-1987, University of North Carolina-Chapel Hill.

RESEARCH:

Genetic abnormalities that cause human brain tumors

Medulloblastoma, a cancer that arises in the developing cerebellum, is the most common solid tumor in children. Medulloblastomas result from defects in signal transduction pathways governing the growth and differentiation of neural stem cells. A barrier to improving patient treatment is collateral damage to the developing nervous system caused by radiation and chemotherapy. The overall objective of Dr. Fults's current research is to identify signaling molecules that mediate the genesis and progression of medulloblastoma. To do this, he is using a mouse model of medulloblastoma that he developed using the RCAS/tv-a system. This system utilizes a retroviral vector (RCAS), derived from avian leukosis virus (ALV), and a transgenic mouse line (Ntv-a) that produces TV-A (the cell surface receptor for ALV) under control of the Nestin gene promoter. Nestin is an intermediate filament protein expressed by neuronal and glial progenitor cells. This system makes it possible to express exogenous proteins in nestin-expressing neural progenitor cells inside the brain of live mice. Dr. Fults found that activation of the Sonic Hedgehog signaling pathway in neural stem cells of the cerebellum induces medulloblastoma formation. Tumor induction is enhanced by insulin-like growth factors, oncogenic transcription factors (Myc proteins), and the anti-apoptotic protein Bcl-2. The long-range benefit of this research will be the identification of potential targets for anti-cancer drugs or future gene therapy strategies. Insights into the molecular pathogenesis of medulloblastoma will also be directly relevant to brain development.

Selected Publications

McCall, T.D., Pedone, C.A., and Fults, D.W. (2007) Apoptosis Suppression by Somatic Cell Transfer of Bcl-2 Promotes Medulloblastoma Formation in Mice. Cancer Research, 67:5179-5185.

Browd, S.R., Kenney, A.M., Gottfried, O.N., Yoon, J.W., Walterhouse, D., Pedone, C.A., and Fults, D.W. (2006) N-myc Can Substitute for Insulin-like Growth Factor Signaling in a Mouse Model of Sonic Hedgehog-Induced Medulloblastoma. Cancer Research, 66:2666-2672.

Di, C., Liao, S., Adamson, D.C., Parrett, T.J., Broderick, D.K., Shi, Q., Lengauer, C., Cummins, J.M., Velculescu, V.E., Fults, D.W., McLendon, R.E., Bigner, D.D., and Yan, H. (2005) Identification of OTX2 as a Medulloblastoma Oncogene Whose Product can be Targeted by All-Trans-Retinoic Acid, Cancer Research, 65:919-924.

Rao, G., Pedone, C.A., Del Valle, L., Reiss, K., Holland, E.C., and Fults, D.W. (2004) Sonic Hedgehog and Insulin-Like Growth Factor Signaling Synergize to Induce Medulloblastoma Formation from Nestin-Expressing Neural Progenitors in Mice. Oncogene, 23:6156-6162.

Rao, G., Pedone, C.A., Coffin, C.M., Holland, E.C., and Fults, D.W. (2003) c-Myc Enhances Sonic Hedgehog-Induced Medulloblastoma Formation from Nestin-Expressing Neural Progenitors in Mice. Neoplasia, 5:198-204.

Fults, D., Pedone, C., Dai, C., and Holland, E.C. (2002) MYC Promotes the Proliferation of Neural Progenitor Cells in Culture and In Vivo. Neoplasia, 4:32-39.

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