# Single-Cell Transcriptomic Analysis to Identify Drivers of Pulmonary Fibrosis

> **NIH NIH K08** · NORTHWESTERN UNIVERSITY · 2020 · $163,296

## Abstract

PROJECT SUMMARY
This proposal for a K08 Award is motivated by two overarching goals: 1) to support the scientific and professional
development of the candidate, Dr. Paul Reyfman, towards achieving his career goal of succeeding as a physician
scientist and independent investigator with expertise in systems biology approaches applied to the study of
chronic lung disease, and 2) to investigate whether single-cell transcriptomic profiling can provide novel insights
into the pathobiology of pulmonary fibrosis. Pulmonary fibrosis is a deadly and progressive condition for which
diagnostic approaches remain imprecise and effective therapies are lacking. Together with his mentors, Drs.
Scott Budinger and Luís Amaral, the candidate has developed a comprehensive training plan that will ensure Dr.
Reyfman acquires new knowledge and proficiencies in developing hypotheses, designing and completing
experiments, analyzing data, and communicating findings to the scientific community. As an essential component
of this training plan, the candidate will employ systems biology approaches to developing tools for analysis of
single-cell transcriptomic datasets generated from patients with pulmonary fibrosis.
Single-cell transcriptomic profiling is increasingly used to investigate the pathobiology of disease in humans and
as a basis for developing novel biomarkers of disease. Developing and validating tools for analyzing the rapidly
growing quantity of single-cell transcriptomic data is as much of a challenge as refining techniques for generating
data from healthy and diseased tissues. In particular, it is not known whether analysis of single-cell RNA
sequencing (scRNA-Seq) and single-nucleus RNA sequencing (snRNA-Seq) data can be used to quantify
accurately the cellular composition of the lung and to identify gene expression differences between health and
pulmonary fibrosis. Our preliminary data suggest that scRNA-Seq of lung identifies profibrotic gene expression
in patients with pulmonary fibrosis that is heterogeneous between individuals. We also found that scRNA-Seq
undersampled certain constituent lung cellular populations. Accordingly, we designed this proposal to test the
hypothesis that single-cell transcriptomic analysis of lung samples from patients with pulmonary fibrosis can be
used to identify disease endotypes. In Specific Aim 1, the candidate will determine whether snRNA-Seq enables
quantification of the cellular composition of the lung during pulmonary fibrosis. In Specific Aim 2, the candidate
will develop tools for using scRNA-Seq performed on specimens obtained from patients with SSc-ILD and normal
controls to gain novel insights into disease pathobiology. Over the course of this award, the candidate will gain
new skills including in generating snRNA-Seq from cryopreserved lung tissue, in lung stereology, in RNA in situ
hybridization, in analysis of complementary genomic datasets, and in incorporation of clinical phenotypic
information into genomic a...

## Key facts

- **NIH application ID:** 9892329
- **Project number:** 1K08HL146943-01A1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Paul A Reyfman
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $163,296
- **Award type:** 1
- **Project period:** 2020-02-20 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9892329

## Citation

> US National Institutes of Health, RePORTER application 9892329, Single-Cell Transcriptomic Analysis to Identify Drivers of Pulmonary Fibrosis (1K08HL146943-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9892329. Licensed CC0.

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