My primary research interest is to understand the emerging role of neuronal activity in childhood cancer. Neurofibromatosis-1 (NF1) is a cancer predisposition syndrome; children born with mutations in the NF1 tumor suppressor gene are predisposed to nervous system neoplasms [e.g., optic pathway gliomas (OPG) and malignant peripheral nerve sheath tumors (MPNST)]. Using a mouse model of NF1-OPG, I uncovered, for the first time, that neuronal activity can drive the initiation of nervous system cancer (Pan et al., Nature, 2021). Moreover, I found that the cancer-predisposing Nf1 mutation synergizes with neuronal activity to initiate OPG.

At MD Anderson, my first objective will be to expand on my...

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My primary research interest is to understand the emerging role of neuronal activity in childhood cancer. Neurofibromatosis-1 (NF1) is a cancer predisposition syndrome; children born with mutations in the NF1 tumor suppressor gene are predisposed to nervous system neoplasms [e.g., optic pathway gliomas (OPG) and malignant peripheral nerve sheath tumors (MPNST)]. Using a mouse model of NF1-OPG, I uncovered, for the first time, that neuronal activity can drive the initiation of nervous system cancer (Pan et al., Nature, 2021). Moreover, I found that the cancer-predisposing Nf1 mutation synergizes with neuronal activity to initiate OPG.

At MD Anderson, my first objective will be to expand on my initial findings and elucidate the mechanisms of neuronal activity-driven OPG pathogenesis. NF1 mutations also predispose patients to peripheral nerve cancers such as MPNST, raising the intriguing possibility that neuronal activity also drives MPNST development. Based on my previous findings in the central nervous system (Pan et al., Genes & Dev., 2018; Pan et al., Oncotarget, 2017) that parallel findings in the peripheral nervous system, my second objective is to understand the role of neuronal activity in MPNST development. Last, my ongoing study suggests that Nf1 mutations in glial cells lead to preneoplasia and neurological deficits, which could be exacerbated by chemotherapy. My third objective is to determine how Nf1 mutations lead to these glial deficits, whether these glial deficits lead to neurotoxicities and whether chemotherapy affects the same pathways.

My lab will perform these studies using neuromodulatory approaches, cell/molecular biology, and genetically engineered mouse models. Together, the goal of my lab will be to provide insights into the prediction, prevention, and treatment of childhood nervous system cancer, with an initial focus on the NF1 cancer predisposition syndrome, and to further our understanding of mechanisms involved in chemobrain.

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