Current Research

Cancer is a disease phenotype often caused by abnormal, uncontrolled cell division. In adults, external factors, such as lifestyle choices, environmental exposures, or occupational hazards commonly underlie tumorigenesis. In children, however, these external factors play a smaller role. Instead, pediatric cancer is thought to arise from a block of developmental maturation. Therefore, effectively treating pediatric cancer will require a thorough knowledge of normal development, including the cellular function of the genes involved.

For example, in medulloblastoma, a highly aggressive embryonic brain tumor, a differentiation block in distinct progenitor cell types gives rise to fo­ur tumor subgroups. Each subgroup has its own clinical features, prognosis, and treatment options. Although 70% of diagnosed children survive over five years, current treatments severely compromise quality of life. Learning more about medulloblastoma disease modalities in relation to their developmental origins will guide patient-specific treatment, increasing remission rates and reducing long-term toxicity. Researchers have identified probable genetic causes using -omic analyses of patient samples. However, rigorous functional validation of putative disease-causing genes and the corresponding cell states is still required. By studying basic neural development, we may better understand pediatric tumor initiation and progression. Our group's long-term goal is to understand normal brain development and elucidate the progression to malignancy. We use induced pluripotent stem cell models and mouse models investigate the role of oncogenes and tumor suppressor genes during development and tumorigenesis. Ultimately, we want to develop mechanism-of-action-based treatments with reduced toxicity for children with brain tumors.

 

Kutscher Fig1

Figure 1. Early progenitors migrate out of the developing rhombic lip.

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Latest Revision: 2020-03-10
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