# Functional Validation of Intracranial Aneurysm Risk Genes

> **NIH NIH R01** · YALE UNIVERSITY · 2020 · $603,007

## Abstract

Intracranial aneurysms (IA) represent a significant health issue in the US and worldwide. Their rupture leads to
intracranial hemorrhage, with devastating outcomes: 30% of patients with ruptured IA die within a month of the
initial event, and 50% of survivors are left with severe neurological deficits requiring long-term care. In our
previous studies, we completed a series of genome-wide association studies (GWAS), which identified several
IA risk loci containing candidate IA risk genes. We now propose to investigate the biological significance of select
candidate genes using genome editing in human endothelial and vascular smooth muscle cell lines, and validate
these findings in zebrafish and mouse, two model organisms that are ideal for genetic manipulations and
analyses of brain vasculature. The proposed studies will establish the mechanisms by which modulation of gene
dosage may enhance risk of aneurysm formation, testing to the hypothesis that they impact vascular
homeostasis and vessel tone regulation. If successful, these studies will stimulate future research into rational
and molecularly informed therapeutic approaches for IA.

## Key facts

- **NIH application ID:** 9857083
- **Project number:** 5R01NS111935-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** MURAT GUNEL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $603,007
- **Award type:** 5
- **Project period:** 2019-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9857083

## Citation

> US National Institutes of Health, RePORTER application 9857083, Functional Validation of Intracranial Aneurysm Risk Genes (5R01NS111935-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9857083. Licensed CC0.

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