# SOX17/RUNX1 Axis Regulates Endothelial Cell Fate in the Pathogenesis of Pulmonary Arterial Hypertension

> **NIH NIH R01** · RHODE ISLAND HOSPITAL · 2022 · $410,000

## Abstract

Project Summary/Abstract:
Pulmonary arterial hypertension (PAH) is a progressive disease characterized by an obliterative vasculopathy of
the distal pulmonary circulation. Adverse structural remodeling and increased pulmonary vascular resistance
result in cardiac hypertrophy and ultimately failure of the right ventricle, with annual mortality averaging 10%.
Current therapies can improve symptoms and delay disease progression, but there is no cure. There is a critical
need to develop new therapies that effectively halt and reverse the disease by targeting the cellular and
molecular mechanisms underlying the pathophysiology of PAH. In Sox17 mutant PAH patients, we postulate
that loss-of-function mutations in the Sox17 gene result in insufficient upregulation of Sox17 during normal
reparative responses to vascular injury allowing increased RUNX1 signaling to drive aberrant angiogenesis.
Thus, our central hypothesis is that loss of repression of Runx1 by endothelial SOX17 predisposes to the
development of PAH through impaired arterial endothelial differentiation and aberrant angiogenesis. To test our
hypothesis, we plan the following specific aims: Aim 1. Determine if endothelial SOX17 deficiency leads to higher
susceptibility of developing PAH. Aim 2. Determine if SOX17/RUNX1 imbalance leads to impaired arterial
differentiation and aberrant angiogenesis following SuHx-PH induction. Aim 3: Determine if Sox17 mutant PAH
patient iPSC-derived ECs have impaired arterial differentiation and defective angiogenic capability.

## Key facts

- **NIH application ID:** 10521366
- **Project number:** 1R01HL158841-01A1
- **Recipient organization:** RHODE ISLAND HOSPITAL
- **Principal Investigator:** JAMES Raymond KLINGER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $410,000
- **Award type:** 1
- **Project period:** 2022-08-25 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10521366

## Citation

> US National Institutes of Health, RePORTER application 10521366, SOX17/RUNX1 Axis Regulates Endothelial Cell Fate in the Pathogenesis of Pulmonary Arterial Hypertension (1R01HL158841-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10521366. Licensed CC0.

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