# Metabolic Reprogramming in Laryngotracheal Stenosis

> **NIH NIH R21** · JOHNS HOPKINS UNIVERSITY · 2020 · $163,750

## Abstract

Summary
Dr. Alexander Hillel is a faculty member in the Department of Otolaryngology-Head & Neck Surgery at the
Johns Hopkins School of Medicine where his clinical practice is dedicated to the medical and surgical
management of voice and airway disorders. With the support of an Early Career Research Award, Dr. Hillel
seeks to better understand metabolic mechanisms of laryngotracheal stenosis (LTS) and apply regenerative
medicine techniques to its treatment. Specifically, Dr. Hillel will be focusing on glutamine metabolism and
targeted inhibition of glutamine as a novel approach to treating LTS in vitro on human LTS-scar fibroblasts and
in vivo in a validate mouse model of LTS. As a part of this study, he plans to utilize a drug-eluting stent to
target these metabolic mechanisms in a preclinical model. Aim 1 will be performed in mice to determine the
ability of 6-diazo-5-oxo-l-norleucine (DON), a glutamine inhibitor, to prevent fibrosis. Systemic DON therapy
will be compared with topical DON administration via a drug eluting stent. One of the enzymes DON blocks is
glutaminase, which converts glutamine into glutamate. Aim 2 will specifically investigate glutaminase inhibition
in human tracheal fibroblasts in vitro and in LTS mice in vivo. Preclinical validation of glutamine inhibition as a
treatment for LTS is a critical step prior to translation to human studies.

## Key facts

- **NIH application ID:** 9959389
- **Project number:** 5R21DC017225-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Alexander Hillel
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $163,750
- **Award type:** 5
- **Project period:** 2018-07-05 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9959389

## Citation

> US National Institutes of Health, RePORTER application 9959389, Metabolic Reprogramming in Laryngotracheal Stenosis (5R21DC017225-03). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9959389. Licensed CC0.

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