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 research is to identify signaling molecules that induce medulloblastoma formation and to target these molecules therapeutically to maximize tumor growth suppression and minimize treatment-related neurotoxicity. 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 stem cells inside the brain of live mice. Dr. Fults found that activation of the Sonic Hedgehog (SHH) signaling pathway in cerebellar neuron progenitors induces medulloblastoma in mice and that the tumors closely mimic the human disease. Tumor induction can be enhanced by cell growth factors Hepatocyte Growth Factor (HGF) and Insulin-like Growth Factor-II (IGF-II), oncogenic transcription factors (Myc proteins), and the anti-apoptotic protein Bcl-2. Dr. Fults is also using this mouse model as a preclinical testing platform for therapies that target SHH and HGF signaling specifically. His lab group has shown that an HGF neutralizing monoclonal antibody or a small molecule that inhibits SHH signaling significantly prolongs the survival of mice, in which medulloblastomas are induced by RCAS-mediated gene transfer.

Selected Publications

Binning, M.J., Niazi, T., Pedone, C.A., Lal, B., Eberhart, C.G., Kim, K.J., Laterra, J., and Fults, D.W. (2008) Hepatocyte Growth Factor and Sonic Hedgehog Expression in Cerebellar Neural Progenitor Cells Costimulate Medulloblastoma Initiation and Growth. Cancer Research, 68:7838-7845.

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.

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