# Targeting the Amino Acid Transporter SLC7A5 for Treatment of Pulmonary Fibrosis

> **NIH NIH R56** · WASHINGTON UNIVERSITY · 2022 · $201,767

## Abstract

PROJECT SUMMARY
Idiopathic Pulmonary Fibrosis (IPF) constitutes a tremendous burden to public health. IPF is a rapidly progressive
lung disease that results from the aberrant accumulation of extracellular matrix proteins (ECM) in fibroblasts with
an estimated survival of 3-4 years. Amino acids are required to provide the critical biomass for proliferating
fibroblasts. The varied mechanisms controlling amino acid transport and metabolism represent a key opportunity
for drug development and precision medicine. SLC7A5 (Solute Carrier Family 7 Member 5) mediates the uptake
of essential amino acids primarily leucine and efflux glutamine out of the cell. As leucine is critical for
the activation of mTOR and aberrant mTOR activation is a hallmark of pulmonary fibrosis, collectively our
preliminary findings motivate our novel hypothesis that SLC7A5 promotes myofibroblast differentiation, mTOR
activation, apoptosis resistance and reduce mitochondrial DNA damage, and by targeting SLC7A5 which could
capable of abrogating multiple facet of fibrosis progression, may represent a efficacious approach towards
developing new therapeutic strategies to treat fibroproliferative diseases. These questions will be addressed by
3 highly interrelated Specific Aims. Aim 1. We will define the biological roles, metabolic and molecular
mechanism(s) by which SLC7A5 regulate profibrotic TGF-β signaling and whether the induction of apoptosis by
inhibiting SLC7A5 “chemosensitize” fibrotic foci. Aim 2. We will elucidate the critical role of SLC7A5 in
mitochondrial fitness and metabolism. We will determine whether activation of apoptosis or suppression of
mTOR by SLC7A5 inhibition impairs mitochondrial fitness. Aim 3. We will determine the in vivo efficacy of
targeting SLC7A5 in a therapeutic model of lung fibrosis and aging. The completion of these specific aims will
provide important mechanistic as well as preclinical information on the role(s) of SLC7A5 in mediating the
fibroproliferative actions of TGF-β and a new therapeutic approach for the treatment of pulmonary fibrosis.

## Key facts

- **NIH application ID:** 11059394
- **Project number:** 7R56HL158549-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Malay Choudhury
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $201,767
- **Award type:** 7
- **Project period:** 2022-09-07 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11059394

## Citation

> US National Institutes of Health, RePORTER application 11059394, Targeting the Amino Acid Transporter SLC7A5 for Treatment of Pulmonary Fibrosis (7R56HL158549-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11059394. Licensed CC0.

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