The Fults Lab
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 progenitor 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 progenitor cells of the cerebellum induces medulloblastoma formation. Tumor induction is enhanced by activation of insulin-like growth factor (IGF) signaling and over-expression of the oncogenic transcription factors, c-Myc and N-Myc. 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.