# Mechanisms of ERG in Endothelial Activation

> **NIH NIH R01** · UNIVERSITY OF ARIZONA · 2021 · $382,955

## Abstract

ABSTRACT
Cardiovascular diseases are the most frequent cause of death worldwide and, given the central role of
prolonged endothelial activation in vascular disease, interventions that dampen the molecular drivers of this
process would have far-reaching consequences to improve human health. Still, the development of therapies
to specifically target vascular inflammation requires that the mechanisms driving this process be understood at
the molecular level in cells exposed to disease-relevant conditions. The long-term goal of this application is to
deconstruct the molecular mechanisms that govern healthy and pathogenic endothelial cell traits in human
cells so that these processes may be exploited for human health. The overall objective of this application is to
investigate the molecular attributes that fine-tune how the endothelial-specific transcription factor ERG steers
endothelial cell gene expression towards healthy or diseased states. Importantly, this application combines
traditional molecular approaches with the power of genomics so that targeted hypotheses may be tested on the
genome-wide scale. The central hypothesis is that ERG's transcriptional activity is essential for healthy
endothelial cell function, and molecular interactions altering its function are direct links to vascular disease. The
central hypothesis will be tested through investigation of three specific aims. The first will identify specific
partners of ERG activity that depend on upstream signaling cascades present in inflammation. The second will
identify direct transcription targets of ERG that perpetuate its pro- and anti-inflammatory functions. Finally, the
third will identify the extent to which ERG directs endothelial cell traits downstream of two different
hemodynamic waveforms that distinguish inactive from activated vascular locales in vivo. Experiments to test
these hypotheses will utilize human aortic endothelial cells to maximize the translatability of the findings to
human genetics research and drug development pipelines. The approach is innovative because it uses
genomics to test targeted, molecular hypotheses, and because it will test novel relationships among proteins
that have not been considered in vascular health and disease. The proposed work will provide molecular
insights to inform the development of novel intervention strategies to improve vascular health and
cardiovascular disease.

## Key facts

- **NIH application ID:** 10151628
- **Project number:** 5R01HL147187-03
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** CASEY E ROMANOSKI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $382,955
- **Award type:** 5
- **Project period:** 2019-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10151628

## Citation

> US National Institutes of Health, RePORTER application 10151628, Mechanisms of ERG in Endothelial Activation (5R01HL147187-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10151628. Licensed CC0.

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