# Pathogenesis of Vascular Anomalies with GNAQ mutations

> **NIH NIH R01** · CINCINNATI CHILDRENS HOSP MED CTR · 2024 · $608,559

## Abstract

PROJECT SUMMARY/ ABSTRACT:
Hyperactive, postzygotic mutations in the GNAQ gene (encoding for Gaq proteins) have been identified in
vascular anomalies. Patients affected by this class of vascular anomalies experience extensive disfigurement
and can develop a life-threatening coagulopathy termed Kasabach-Merritt Phenomenon (KMP). Despite these
genetic findings, animal models for GNAQ-related vascular anomalies and KMP do not exist. This has severely
hindered the preclinical development of effective targeted therapies for these patients.
In our preliminary experiments we generated a transgenic murine model of mutant hyperactive GNAQ-driven
vascular anomaly which recapitulates common histopathological findings in patients and a coagulopathy
reminiscent of KMP, a potentially lethal disease complication. Furthermore, our studies showed that in patient-
derived lesional tissue with GNAQ Q209L mutation, the MAPK/ERK signaling pathway is hyperactive as well as
increased EC proliferation. We have exciting data that the MEK/ERK inhibitor Trametinib extended the life span
of GNAQ mutant mice suggesting this may be a promising therapy for patients.
To date there are no studies examining the role of mutant active GNAQ (p.Q209L) in vascular development and
disease. This proposal will culminate with the development of innovative in vivo, in vitro, and Vessel-on-Chip
models that we will use for the identification of cellular and molecular mechanisms implicated in vascular disease.
Furthermore, with our powerful murine model we are uniquely positioned to develop a comprehensive research
program to investigate the GNAQ role in vascular lesion formation and expansion with the goal of identifying
highly needed therapeutic targets for vascular anomalies and related complications such as coagulopathies.
Additionally, our studies will provide cellular and mechanistic insights to advance our understanding of
pathological and physiological vessel formation and size maintenance.

## Key facts

- **NIH application ID:** 10868134
- **Project number:** 1R01HL167700-01A1
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** ELISA BOSCOLO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $608,559
- **Award type:** 1
- **Project period:** 2024-04-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10868134

## Citation

> US National Institutes of Health, RePORTER application 10868134, Pathogenesis of Vascular Anomalies with GNAQ mutations (1R01HL167700-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10868134. Licensed CC0.

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