ALSF Researcher Spotlight: Nicole Brossier, MD/PhD

July 15, 2022

Nicole Brossier, MD/PhD, of Washington University was awarded an ALSF Young Investigator grant in 2019. Her project, Defining the Molecular Mechanisms Underlying Pediatric Brain Tumor Penetrance, would address the inability to provide accurate risk assessment for developing optic pathway gliomas (OPGs) for children born with a germline neurofibromatosis type 1 (NF1) gene mutation. She planned to perform an analysis of the potential cells of origin for these tumors using a novel collection of NF1 mutant mice genetically engineered to harbor different NF1 patient germline NF1 gene mutations.

During the course of the project, Dr. Brossier identified three functionally and molecularly distinct populations of mouse TVZ (Third Ventricle Zone) NPCs (Neural Stem/Progenitor cells), one of which (“M” cells) exhibits the highest clonogenic incidence, proliferation, and abundance during embryogenesis. This suggests that “M” cells may be the cell of origin for NF1 OPG. She further demonstrated that the proliferation of TVZ NPCs, including “M” cells, dramatically decreases after birth. The germline NF1 mutations that support NF1 OPG formation in a tumor-bearing model were found to increase the proliferation of TVZ NPCs during embryogenesis. NF1 germline mutation did not affect the proliferation of NPCs in other germinal zones in the brain at this age. Overall, this supports that both neurodevelopmental and genetic factors may control when and where gliomas form in children with NF1.

In the next phase of this project, Dr. Brossier will directly assess the ability of “M” cells versus other TVZ NPCs, such as “V” and “D” cells, to form gliomas following biallelic NF1 loss. She aims to determine the molecular differences between TVZ NPCs with germline mutations that support tumor formation in murine models (e.g. R681X, R1278P) and those that do not (G848R). She is also interested in how environmental exposures may interact with mutation in these cells to affect tumor formation. Dr. Brossier has also shared resources through ALSF’s Childhood Cancer Research Resources (CCRR) portal. “I think it’s important for researchers to share data, particularly with these large computational data sets, in order to prevent duplicated efforts. Building off of each other’s results allows faster research progress, which ultimately is a good thing for kids with cancer,” she explains. We appreciate her efforts to support collaboration and accelerate progress!