# Mechanisms regulating hemangioendothelioma: A plastic surgeon's challenge

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 2020 · $338,625

## Abstract

Project Summary
Hemangiomas are the most common tumors in infants. These tumors can threaten the child's life (1%),
threaten the development of vital structures (10%) and cause residual deformity in 50% of affected children.
The majority occur in the head and neck area resulting in obvious physical deformity that causes tremendous
distress for parents. Despite these significant complications, the majority of affected children do not receive
treatment because of the high risks associated with current pharmacologic therapies. The absence of safe
therapeutic alternatives is a critical barrier to care and good clinical outcomes for children with hemangiomas.
In the previous cycle of funding we discovered markedly elevated levels of microRNA (miR)126 in the urine of
children with proliferating hemangiomas indicating its potential usefulness as a biomarker. It is also markedly
upregulated (104 x) in our validated murine model using EOMA cells and transdermal delivery of miR 126
inhibitor resulted in complete tumor regression in the murine model. miR126 is the predominant miR transcript
expressed by endothelial cells during development and the transcription factor GATA binding protein 2
(GATA2) is critical driver of fetal endothelial cell development. Both are upregulated in EOMA cells, which
supports the conceptual paradigm that endothelial cells in hemangiomas retain a persistent fetal phenotype,
i.e. they are fetal rests. This proposal will establish miR126 as a critical driver of hemangioma development
and proliferation and GATA2 as a key transcriptional regulator of miR126 biogenesis. We have previously
reported that a standardized natural berry extract (NBE) can effectively limit hemangioma development and
proliferation using the EOMA model. This safe nutritional intervention also inhibits the GATA2/miR126 axis in
EOMA cells. This proposal will test the ability of NBE to inhibit hemangioma proliferation in the murine model
and in children with hemangiomas. Changes in urinary levels of miR126 in response to NBE therapy will be
measured to establish utility as a biomarker. The innovation in this proposal includes: the use of important
contextual cues from fetal development to inform lines of investigation, establishing the critical significance of
miR regulation of hemangioma proliferation, the identification of a safe nutritional intervention with
pharmacokinetic data to determine first in human dosing, and the identification and testing of a biomarker for
hemangioma. Successful completion of this proposal will change clinical management of hemangioma by
making treatment safely available to all affected children in an effort to prevent death, disability or deformity
caused by these tumors.

## Key facts

- **NIH application ID:** 10012938
- **Project number:** 5R01GM095657-09
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Gayle M Gordillo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $338,625
- **Award type:** 5
- **Project period:** 2011-02-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10012938

## Citation

> US National Institutes of Health, RePORTER application 10012938, Mechanisms regulating hemangioendothelioma: A plastic surgeon's challenge (5R01GM095657-09). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10012938. Licensed CC0.

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