Single Cell Transcriptomic Analysis of Pulmonary Fibrosis

  • Reyfman, Paul Andrew (PD/PI)

Project: Research project

Project Details


This proposal for an ATS Foundation Pulmonary Fibrosis Research Grant 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 singlecell
transcriptomic profiling can provide novel insights into the biology 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 incorporating 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 to develop novel biomarkers of disease. Multiple techniques for single-cell transcriptomic
profiling have been developed, including single-cell RNA sequencing (scRNA-Seq) and single-nucleus RNA
sequencing (snRNA-Seq), but it is not known which technique is superior for investigating the pathobiology
of pulmonary fibrosis, or whether these techniques can be used on clinically obtained specimens to develop
biomarkers for pulmonary fibrosis. Our preliminary data suggest that scRNA-Seq of lung identifies profibrotic
gene expression in patients with pulmonary fibrosis that is heterogenous between individuals. We also found
that scRNA-Seq undersampled certain constituent lung cellular populations. Accordingly, we designed this
proposal to test the hypotheses that snRNA-Seq is superior to scRNA-Seq for estimating the lung cellular
composition and performs comparably for identifying transcriptomic changes between healthy and diseased
states, and that biomarker development for pulmonary fibrosis using samples obtained routinely in clinical
care is feasible. In Specific Aim 1, the candidate will determine whether snRNA-Seq is superior to scRNA-Seq
for providing insight into the pathobiology of pulmonary fibrosis. In Specific Aim 2, the candidate will
determine whether scRNA-Seq can identify transcriptional changes in alveolar macrophages from patients
with pulmonary fibrosis from SSc-associated interstitial lung disease. Over the course of this award, the
candidate will learn gain new skills including in snRNA-Seq, analyzing complementary genomic datasets, and
incorporating clinical phenotypic information into genomic analyses. Accomplishing the proposed work will
provide a rigorous training program for Dr. Reyfman and will provide insights that could lead to improved
therapies for patients with pulmonary fibrosis.
Effective start/end date12/15/1812/14/21


  • ATS Foundation Inc. (AGMT 12/13/18)


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