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Research Description:
Dr. Fults is a neurosurgeon whose clinical practice is focused on the surgical treatment of patients with brain tumors. His laboratory research is focused on the pathogenesis of medulloblastoma, a malignant brain tumor that afflicts children. Aggressive treatment of medulloblastoma, combining surgery with radiation and chemotherapy, give five-year survival rates exceeding 70%, depending upon clinical risk factors such as patient age and tumor size. Despite these encouraging statistics, treatment-related toxicity can cause cognitive impairment, skeletal growth retardation, hormonal problems, as well as psychiatric and behavioral disturbances in long-term survivors. Thus, there is a critical need to enhance treatment specificity by identifying molecular targets that can be exploited to maximize tumor growth suppression and minimize collateral brain damage. Dr. Fults studies how defects in signaling molecules that normally govern the growth and differentiation of neural stem cells cause medulloblastoma. His approach utilizes a mouse model, in which oncogenes can be transferred and expressed in neural stem cells in the cerebellum of newborn mice. In this way, specific signaling pathways are activated in those cells to determine whether tumors form. Dr. Fults has found that activation of the Hedgehog signaling pathway, which is important in normal brain development, induces tumors in mice that closely mimic human medulloblatomas. Tumor induction can be enhanced by cell growth factors (hepatocyte growth factor and insulin-like growth factor), 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. Insights into the molecular pathogenesis of medulloblastoma will also be directly relevant to brain development.
Research Keywords:
Brain Tumor, Medulloblastoma, Hedgehog signaling, neural stem cells