# Neurofibromin 1 as a novel regulator of lipid metabolism

> **NIH NIH F99** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $49,974

## Abstract

PROJECT SUMMARY
High grade gliomas (pHGGs) represent the greatest number of solid tumors in the pediatric population, and now
are the greatest cancer related cause of death. Within the past 20 years, treatment progress has remained
stagnant, as 5-year survival rates remain less than 20%. Ras signaling has been shown to be highly upregulated
in many pHGGs, although Ras mutations are very rare. The role of negative regulators of Ras signaling, Ras
GAPs, in pHGGs remain vastly understudied. We discovered that Neurofibromin 1 (Nf1) is a Ras GAP commonly
mutated in 10% or higher of pHGGs. Additionally, 1 in 3000 individuals per year are born with Neurofibromatosis
Type I, a tumor predisposition syndrome with somatic heterozygous NF1 mutation. These individuals are at
greater risk for developing a number of cancers, including brain tumors. We leveraged pHGG transcriptomic and
proteomic datasets and GSEA pathway analysis and identified that alterations in cellular metabolism correlate
with NF1 loss in pediatric high grade gliomas, specifically through vast changes in lipid content.
I hypothesize that NF1 is a critical regulator of lipid metabolism, and that metabolic intervention could be used
to treat NF1 driven gliomas. My goal during the remainder of my graduate training (F99 phase) is to elucidate
how NF1 loss alters fatty acid/lipid metabolism, and whether targeting this phenotype in pHGG models is
efficacious. Upon finishing my graduate training, I will identify a post-doctoral mentor (K00) and further
investigate the metabolic roles of NF1 on brain tumor epigenetics. The proposed project leverages in vitro and
in vivo systems to study a distinct metabolic phenotype at the cellular and tumor levels. Our research will inform
a molecular mechanism and translational relevance for a role of NF1 in lipid metabolism. This data could also
be applicable to other cancer types and tumor predisposition syndromes. Combined together, the two phases of
this award will provide me with the means to establish myself as a successful cancer researcher and enable
me to lay the foundation for my own independent cancer research laboratory predicated on intertwined
study of brain tumor biology, neuroscience, and metabolism.

## Key facts

- **NIH application ID:** 11075431
- **Project number:** 1F99NS141404-01
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Taylor Gatesman
- **Activity code:** F99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $49,974
- **Award type:** 1
- **Project period:** 2024-09-20 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11075431

## Citation

> US National Institutes of Health, RePORTER application 11075431, Neurofibromin 1 as a novel regulator of lipid metabolism (1F99NS141404-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11075431. Licensed CC0.

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