# Mechanosensing in lung fibrosis

> **NIH NIH R01** · GEORGIA INSTITUTE OF TECHNOLOGY · 2024 · $545,400

## Abstract

Project Summary
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive disease that results in lung scarring and breathing
difficulty with a median survival of 2-5 years following diagnosis. Although the underlying mechanisms are poorly
understood, fibroblastic foci develop around alveoli as dense regions of extracellular matrix (ECM) and activated
fibroblasts and myofibroblasts. These stiff fibrotic lesions are implicated in the pathogenesis of IPF as poorer
outcomes are observed in patients with more fibroblastic foci. Age is a major risk factor in IPF, and aging
pathways, including the senescence-associated secretory pathway (SASP) and development of apoptosis-
resistant fibroblasts, have been implicated in IPF. However, the interplay between ECM mechanosensing and
aging in IPF remains poorly understood, and this lack of understanding limits the development of therapeutic
agents. The objective of this project is to elucidate the contributions of FAK mechanosensing to ECM remodeling,
senescence, apoptosis-resistance, and SASP in pulmonary fibrosis. Our central hypothesis is that aging-
associated dysregulation of FAK mechanosignaling drives pulmonary fibrosis. We will exploit a novel in vitro 3D
bioengineered microtissue model that mimics healthy and diseased lung tissue to dissect FAK mechanosignaling
in senescent fibroblasts and an IPF-relevant aged mouse model to evaluate inhaled microparticles delivering
FAK inhibitors in alleviating pulmonary fibrosis. Aim 1. Engineer microtissues using human primary fibroblasts
isolated from IPF and healthy donors to model senescence and ECM remodeling in pulmonary fibrosis. Aim 2.
Assess the role of FAK in regulating senescent phenotype, apoptosis, SASP, and ECM remodeling in NHLF and
DHLF-IPF microtissues. Aim 3. Evaluate the therapeutic effects of inhaled microparticles delivering FAK inhibitor
in modulating fibroblast senescence and alleviating pulmonary fibrosis in a bleomycin-induced lung injury model
in aged mice. This research will provide new insights into cell-ECM interactions driving disease and identify
therapeutic targets for the treatment of IPF.

## Key facts

- **NIH application ID:** 10944346
- **Project number:** 1R01HL175067-01
- **Recipient organization:** GEORGIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Andres J Garcia
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $545,400
- **Award type:** 1
- **Project period:** 2024-07-15 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10944346

## Citation

> US National Institutes of Health, RePORTER application 10944346, Mechanosensing in lung fibrosis (1R01HL175067-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10944346. Licensed CC0.

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