# Modeling to Design Treatments for Idiopathic Lung Fibrosis

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2024 · $537,250

## Abstract

PROJECT SUMMARY
Every year in this country 40,000 patients are diagnosed with idiopathic pulmonary fibrosis (IPF), a progressive
and terminal disease caused by excessive extracellular matrix production by myofibroblasts in distributed
lesions, or “fibrotic foci”, throughout the lung. Despite the availability of two FDA-approved drugs that are
considered standard of care, the mortality rate for IPF patients exceeds 30% at four years, and there are no
drugs that halt disease progression, making diagnosis with IPF a death sentence for over 500,000 Americans
living with this disease. Identifying the cells of origin that give rise to myofibroblasts is necessary for finding
treatments that can halt or cure IPF. Based on experimental data and computational simulations from our
research team, we hypothesize that myofibroblasts arise from microvascular pericytes (cells that normally
enwrap capillaries) when heterotypic pericyte-endothelial interactions become disrupted. We further posit that
strategic modulation of kinase-mediated signaling in pericytes can prevent pericyte-to-myofibroblast transitions
and halt the progression of IPF. We propose to combine computational modeling with experiments to study
pericyte-to-myofibroblast differentiation and to investigate how microvessel adaptations in the lung contribute
to IPF. Specifically, we will develop a new agent-based model (ABM) that incorporates logic-based intracellular
signaling networks to simulate cell behaviors and leverages Bayesian inference for rule refinement (Aim 1),
validate the ABM's ability to predict pericyte phenotype transitions and the emergence of fibrotic foci in
response to drugs using the murine bleomycin model of IPF (Aim 2), and bridge murine experiments with
clinical data in order to predict how druggable kinase-driven signaling pathways affect IPF progression via
modulation of pericytes and microvessels (Aim 3). To our knowledge, our proposed studies will be the first to
combine computational modeling with experiments to study microvascular contributors to IPF progression. In
addition to producing a new computational model that is validated for bridging pre-clinical study results to
clinical outcomes, we expect to identify new therapeutic approaches for IPF that target microvascular cells,
previously underexplored but potentially critical contributors to this deadly disease.

## Key facts

- **NIH application ID:** 10871896
- **Project number:** 5R01HL155143-04
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Thomas Harrison Barker
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $537,250
- **Award type:** 5
- **Project period:** 2021-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10871896

## Citation

> US National Institutes of Health, RePORTER application 10871896, Modeling to Design Treatments for Idiopathic Lung Fibrosis (5R01HL155143-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10871896. Licensed CC0.

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