# Uncovering the genomic regulatory network of myofibroblast differentiation in systemic sclerosis-associated interstitial lung disease

> **NIH NIH K08** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $161,136

## Abstract

ABSTRACT
This application is for a Mentored Clinical Scientist Research Career Development Award entitled “Uncovering
the genomic regulatory network of myofibroblast differentiation in systemic sclerosis-associated interstitial lung
disease”, submitted by Dr. Eleanor Valenzi, an Assistant Professor of Medicine within the Division of Pulmonary,
Allergy and Critical Care Medicine at the University of Pittsburgh. The short-term goals detailed in this submission
are designed to help the applicant achieve her long-term objective of becoming an independent physician-
scientist and leader in the field of autoimmune interstitial lung disease (ILD) research. These short-term goals
include (1) advancing knowledge of computational and molecular biology (2) expansion of technical and analytic
tools to effectively perform translational ILD research, and (3) development of leadership skills to obtain
academic independence. This work will be completed in the Division of Pulmonary, Allergy and Critical Care
Medicine at the University of Pittsburgh, a rich research environment with a strong commitment to and proven
track record of fostering the development of physician-scientists. The central objective of this research proposal
is to investigate the gene regulatory networks driving myofibroblast differentiation in systemic sclerosis-
associated interstitial lung disease (SSc-ILD), as myofibroblasts are the key effector cell in fibrosis and no
treatments currently exist to target these cells. Interstitial lung disease is the leading cause of death in systemic
sclerosis, the rheumatic disease with the highest case mortality. The applicant’s prior published work identified
the transcriptome of the SSc-ILD pathogenic myofibroblasts in explanted lung tissues, however the specific gene
regulatory networks driving differentiation of resident fibroblasts to pathogenic myofibroblasts remain unknown.
Additional preliminary data implicates resident pulmonary fibroblasts as the primary source of myofibroblasts,
and the RUNX2/3 transcription factors (TFs) as putative positive regulators of myofibroblast differentiation. The
primary hypothesis is that RUNX2 and RUNX3, in association with specific composite motif TF partners, promote
myofibroblast differentiation and the aberrant myofibroblast phenotype in SSc-ILD. With this proposal, the
applicant will expand on her prior work with the following specific aims: (1) define the epigenetic and
transcriptional programs essential to myofibroblast differentiation, (2) reconstruct the regulatory network of
RUNX2/3 in myofibroblasts, and (3) determine the mechanism by which RUNX2/3 regulate the critical
myofibroblast effector functions of extracellular matrix expression and contractility. This proposal will determine
the SSc-ILD myofibroblast RUNX2/3 gene regulatory program and establish a pipeline for downstream
investigation of the critical implicated transcription factors and the mechanisms by which they regulate the
myofibroblast p...

## Key facts

- **NIH application ID:** 10523340
- **Project number:** 1K08HL161258-01A1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Eleanor Valenzi
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $161,136
- **Award type:** 1
- **Project period:** 2022-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10523340

## Citation

> US National Institutes of Health, RePORTER application 10523340, Uncovering the genomic regulatory network of myofibroblast differentiation in systemic sclerosis-associated interstitial lung disease (1K08HL161258-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10523340. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*