# Genetic and molecular mechanisms of Nf1-dependent neuronal regulation of metabolism

> **NIH NIH R01** · SCRIPPS FLORIDA · 2022 · $27,380

## Abstract

Project Summary
Neurofibromatosis type 1 is a relatively common monogenetic, multisystemic disorder that affects
approximately one in 3,500 individuals worldwide. The causative gene encodes a protein called
neurofibromin (Nf1), which essentially acts as a brake on Ras signaling via Ras-GAP activity. Nf1
affects multiple downstream signaling cascades, including central regulators of metabolism. Prior
studies have suggested that loss of Nf1 may affect metabolism, but the mechanisms, particularly at
the systemic level are unclear. Nf1 effects on metabolic processes may underlie or modulate some of
the symptoms of the disease, such as behavioral alterations and cancer predisposition.
This project will test the mechanisms underlying how loss of Nf1 affects metabolism in vivo, using the
powerful Drosophila model for neurofibromatosis type 1. Upon completion, we will have a clear
picture of: (1) the genes and cellular signaling cascades that regulate metabolism in an Nf1-
dependent manner, (2) how Nf1 functions in neuronal circuits to regulate metabolism through central
control, (3) the neurotransmitters and/or peptides that are involved in the central control of metabolic
regulation, (4) how loss of Nf1 mechanistically regulates peripheral energy stores through the effects
of novel genes. The highly conserved nature of Nf1 and its signaling functions, as well as
fundamental neuronal circuit functional principles, underscores the broad applicability of the results.
Overall, this project will contribute to understanding conserved Nf1 functions in metabolism and
neuronal function, laying the foundation for research into metabolic effects of Nf1 across organisms
and future development of novel therapeutic interventions.

## Key facts

- **NIH application ID:** 10418360
- **Project number:** 1R01NS126361-01
- **Recipient organization:** SCRIPPS FLORIDA
- **Principal Investigator:** Seth M Tomchik
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $27,380
- **Award type:** 1
- **Project period:** 2022-03-01 → 2022-04-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10418360

## Citation

> US National Institutes of Health, RePORTER application 10418360, Genetic and molecular mechanisms of Nf1-dependent neuronal regulation of metabolism (1R01NS126361-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10418360. Licensed CC0.

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