# Mechanisms of Nf1 Pathophysiology Underlying Hyperactivity

> **NIH NIH R01** · SCRIPPS FLORIDA · 2021 · $236,761

## Abstract

Neurofibromatosis type 1 is one of the most common monogenic developmental disorders, affecting ~1 in
3,500 individuals worldwide. Some form of cognitive or neuropsychiatric dysfunction is present in
approximately 50-80% of individuals with NF1, and these are often considered the major causes of lifetime
morbidity. The neurofibromin protein (Nf1) directly inhibits Ras signaling, but also affects several other
signaling cascades (possibly indirectly). The complexity of the signaling cascades implicated in
neurofibromatosis 1, combined with the lack of drugs to target Nf1 directly, highlights the pressing need for
new approaches to target NF1 phenotypes. Uncovering genetic modifers of neurofibromatosis 1-related
cellular dysfunction would provide potential new targets for treating this disorder.
This project will focus on hyperactivity and repetitive behaviors in Drosophila loss of function nf1 mutants. The
large effect size of these behavioral deficits will enable their use it as a readout to unravel both the in vivo
molecular and circuit functions of the neurofibromin protein in a powerful genetic model organism. Specific
aims will investigate how Nf1 loss of function affects hyperactivity/repetitive behaviors, test the signaling and
genetic interactions underlying Nf1 function, probe its role in a putative signaling complex with a novel lipid
signaling interaction partner, and decipher the effects of loss of Nf1 on neuronal circuit excitability and function.

## Key facts

- **NIH application ID:** 10142546
- **Project number:** 5R01NS097237-05
- **Recipient organization:** SCRIPPS FLORIDA
- **Principal Investigator:** Seth M Tomchik
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $236,761
- **Award type:** 5
- **Project period:** 2017-05-01 → 2022-04-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10142546

## Citation

> US National Institutes of Health, RePORTER application 10142546, Mechanisms of Nf1 Pathophysiology Underlying Hyperactivity (5R01NS097237-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10142546. Licensed CC0.

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