# Investigation of pulmonary fibrosis biology in pediatric hematopoietic cell transplant patients

> **NIH NIH R03** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $134,123

## Abstract

Project Summary/Abstract
Allogeneic hematopoietic cell transplantation (HCT) was developed in the 1950’s as a treatment option for life-
threatening malignant and non-malignant diseases. The process involves high dose chemoradiotherapy followed
by intravenous infusion of a donor allograft with the intention of correcting hematopoietic defects or achieving a
graft-versus-malignancy effect. While overall survival has improved, HCT can lead to severe pulmonary injury
due to infection, alloreactivity, or direct chemotherapy toxicity to the lung. Excessive or chronic injury can lead to
pulmonary fibrosis (PF), which is associated with morbidity and premature mortality. The biology of PF involves
inflammation, TGFβ signaling, and epithelial-mesenchymal transition, but additional mechanisms may contribute
in the setting of HCT. An expanding array of molecules are being developed to target PF, thus opening the door
to clinical testing in the pediatric HCT population. However, strategies to select ideal candidates for specific
therapies are currently lacking, precluding children from advances in the field. Therefore, the goal of this R03
proposal is to enhance our ability to identify and treat pediatric HCT patients with or at-risk for PF. To do this, we
will leverage bronchoalveolar lavage (BAL) fluid and paired blood samples obtained from pediatric HCT patients.
In Specific Aim 1, we will determine which patients have PF at the time of BAL based on biopsy, pulmonary
function tests, and chest imaging. We will then identify BAL transcriptomic and proteomic signatures that differ
among patients with vs without PF while accounting for important clinical differences. We will repeat these
comparisons using paired blood samples to see if BAL signatures can be identified using a more readily testable
sample type. In Specific Aim 2, we will follow patients without PF at the time of BAL for 12 months. We will
determine which patients go on to develop PF. We will then compare transcriptomic and proteomic signatures
from the original BAL and blood samples to identify predictors of the future development of PF. Through these
aims, we will gain insight into PF pathobiology in this high risk population. These data will then facilitate early
identification of high-risk patients who may benefit from the rapidly growing pipeline of novel anti-fibrotic
therapies. Overall, this work may increase the safety and accessibility of allogeneic HCT as a treatment for
numerous life-threatening pediatric diseases.

## Key facts

- **NIH application ID:** 10985546
- **Project number:** 1R03HL171423-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Matthew Scott Zinter
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $134,123
- **Award type:** 1
- **Project period:** 2024-08-15 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10985546

## Citation

> US National Institutes of Health, RePORTER application 10985546, Investigation of pulmonary fibrosis biology in pediatric hematopoietic cell transplant patients (1R03HL171423-01A1). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10985546. Licensed CC0.

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