Project Grant R35NS142919

This $877,001 R35 research program award from the National Institute of Neurological Disorders and Stroke (NINDS), under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) grant program, supports research at The Washington University to investigate the cellular and molecular mechanisms underlying the clinical heterogeneity observed in children with neurofibromatosis type 1 (NF1).

The project aims to (1) mechanistically define the multicellular circuits that drive the development and progression of the two most common NF1-associated nervous system problems - low-grade gliomas and neurodevelopmental deficits, and (2) determine how various risk factors modify these multicellular circuits to create the wide variability in clinical symptoms seen in NF1 patients. The research leverages patient-derived cell lines, CRISPR-engineered iPSCs, and mouse models with patient-derived NF1 mutations, along with multi-omic bioinformatic analysis, to establish the etiologic bases for NF1 clinical heterogeneity. The findings are expected to guide the development of more personalized and effective treatment approaches for NF1.