Neuron-cancer crosstalk in nervous system tumors
Recent findings have demonstrated the critical role of neurons in cancer initiation, growth and metastases. These findings contribute to the emerging field of cancer neuroscience. Neurofibromatosis Type 1 (NF1), a cancer predisposition syndrome and neurogenetic disorder, is a valuable platform for understanding the interaction between neurons and neoplastic cells. Individuals affected by NF1 are born with mutations in the NF1 tumor suppressor gene and are predisposed to neoplasms, especially in the nervous system (e.g., optic pathway gliomas [OPG] and malignant peripheral nerve sheath tumors [MPNST]). Using a genetically engineered mouse model (GEMM) of NF1-OPG, we uncovered that neuronal activity synergizes with the germline Nf1 mutation to drive the initiation of NF1-OPG (Pan et al., Nature, 2021). Using a variety of GEMM of NF1, we aim to determine the cellular and molecular mechanisms underlying the neuronal activity-mediated nervous system neoplasms associated with NF1.
Neuron-glia interactions and cognitive function
In neurogenetic disorders such as NF1, the germline mutation affects every cell type including neurons and glial cells. Our ongoing studies suggest that Nf1 mutations lead to dysregulated neuron-glia interactions and neurological deficits, which could be exacerbated by chemotherapy. Using neuroscience approaches and GEMM, we aim to determine how cancer-predisposing mutations lead to deficits in neuron-glial interactions and neurological function, and whether chemotherapy exacerbates the deficits.