# Targeting the Amino Acid Transporter SLC7A5 for Pulmonary Fibrosis

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2024 · $498,780

## 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 and mitophagy resistance and by targeting SLC7A5 which could capable of abrogating
multiple facet of fibroblast activation, 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 detailed role(s) of SLC7A5 mediated mitochondrial
alteration in controlling fibroblast apoptosis and mitophagy. We will also investigate whether SLC7A5 inhibition
induces mitophagy and inhibits lung fibrosis development in the setting of insufficient mitophagy as seen in IPF.
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:** 11060380
- **Project number:** 7R01HL167732-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Malay Choudhury
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $498,780
- **Award type:** 7
- **Project period:** 2024-05-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11060380

## Citation

> US National Institutes of Health, RePORTER application 11060380, Targeting the Amino Acid Transporter SLC7A5 for Pulmonary Fibrosis (7R01HL167732-02). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/11060380. Licensed CC0.

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