# Investigation of TRIM9 in cell shape change in the aging brain

> **NIH NIH R35** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $199,361

## Abstract

PROJECT SUMMARY
Over the past nine years, my lab has focused on the function of the brain enriched E3 ubiquitin
ligase TRIM9. Our interest in TRIM9 originated from our identification of direct interactions
between TRIM9 and the actin polymerase VASP, the exocytic synaptic t-SNARE SNAP25 and
the netrin receptor DCC. This led us to hypothesize that TRIM9 coordinated cytoskeletal and
membrane remodeling during netrin triggered cellular shape change. Our work has shown that
TRIM9 regulates cytoskeletal dynamics and membrane remodeling during several critical stages
of morphogenesis of developing neurons. This includes not only changes in developmentally
relevant stages such as growth cone morphology, and axonal and dendritic branching, but later
morphogenetic stages with synaptic function relevance, such as dendritic spine density. Several
lines of evidence suggest that TRIM9 may continue to play a critical role in the health and function
of the aging neuron. First, TRIM9 enrichment in nervous system continues into adult and is
repressed in the brains of human patients with Parkinson's disease and dementia with Lewy
bodies. Our work has shown that deletion of murine Trim9 results in dramatic cognitive
impairment, specifically in spatial learning and memory. Trim9-deficient mice exhibit increased
neuroinflammation, whereas increasing TRIM9 expression plays neuroprotective roles following
ischemic stroke. Finally, TRIM9 is a novel marker for paraneoplastic cerebellar degeneration.
Here, we propose to expand our investigation into how TRIM9 specifically affects the shape and
function of the aging neuron, and susceptibility to AD.

## Key facts

- **NIH application ID:** 10121328
- **Project number:** 3R35GM135160-01S1
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Stephanie Gupton
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $199,361
- **Award type:** 3
- **Project period:** 2019-12-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10121328

## Citation

> US National Institutes of Health, RePORTER application 10121328, Investigation of TRIM9 in cell shape change in the aging brain (3R35GM135160-01S1). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10121328. Licensed CC0.

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