# The role of Alveolar Epithelial Cell Metabolic Reprogramming in Idiopathic Pulmonary Fibrosis

> **NIH NIH F32** · UNIVERSITY OF PENNSYLVANIA · 2021 · $70,890

## Abstract

Abstract
Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease of unknown cause marked by dysfunctional wound
healing and aberrant fibrotic remodeling of the lung that claims the lives of more than 40,000 Americans each
year. The median age of IPF is 66 years and patients have an average life expectancy of 3 years. The
scientific discovery into this disease has been slow and has resulted in only two FDA approved medications
that do not reverse or cure the disease. In light of the increasing longevity of the American population,
understanding the underlying drivers of this disease is essential. Recently, the critical role of epithelial biology
in the development and progression of this disease has become a high impact question that requires further
elucidation. To address this unmet need, we will utilize a novel preclinical murine model (SftpcI73T) of IPF that
closely recapitulates many aspects of the human disease and permits temporal modeling of subclinical events
in its pathogenesis. Founded in compelling preliminary data, the overall goal of this project is to capitalize on
the aforementioned novel Sftpc model to characterize the metabolic dysfunction in epithelial cells and identify
potential pathways for pharmacologic intervention. In this model, I have found that the alveolar type II
epithelial cell (AT2) undergoes marked changes in metabolism including a shift towards enhanced glycolysis,
alterations in TCA cycle intermediates, and changes in mitochondrial dynamics. From this I hypothesize that
in IPF an acquired deficiency in AT2 cell quality control initiates a cascade of metabolic reprogramming in the
cell that promotes a profibrotic AT2 endophenotype(s) which can initiate, amplify and enhance fibrogenesis.
We will test this hypothesis in two specific aims: 1) Using the SftpcI73T mutant, characterize the scope of AT2
metabolic reprogramming in IPF focusing on mitochondrial function, mitochondrial dynamics, and TCA
intermediate flux. 2) Determine the effect of altered metabolism on AT2 function during fibrogenesis both in-
vitro and in-vivo. The findings from this study will characterize the role of metabolic reprogramming in epithelial
dysfunction and elucidate potential targets for therapeutic intervention. Beyond the scope of IPF, epithelial
dysfunction is an important aspect of chronic and acute lung disease, particularly in light of the COVID-19
pandemic.

## Key facts

- **NIH application ID:** 10313392
- **Project number:** 1F32HL160011-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Luis R Rodriguez
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $70,890
- **Award type:** 1
- **Project period:** 2021-12-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10313392

## Citation

> US National Institutes of Health, RePORTER application 10313392, The role of Alveolar Epithelial Cell Metabolic Reprogramming in Idiopathic Pulmonary Fibrosis (1F32HL160011-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10313392. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*