# Epigenetic Regulation of KLF4 in SSc-associated lung fibrosis

> **NIH NIH K01** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2024 · $119,986

## Abstract

PROJECT SUMMARY / ABSTRACT
 Systemic sclerosis (SSc) is a rare and devastating connective tissue disorder that results in fibrosis and
vascular abnormalities that can affect the skin, lungs, gastrointestinal tract, heart, and kidneys. The underlying
mechanisms are complex and largely unknown, and no effective treatment exists to stop the progression of
fibrosis in SSc or reverse it. Interstitial lung disease ILD) associated with SSc is a leading cause of death inSSc
patients. The focus of this proposal is on the epigenetic regulation of KLF4, a transcription factor with anti-fibrotic
function in pulmonary fibroblasts (pFBs). KLF4 is downregulated during active fibrosis. The goal is to identify
targetable epigenetic factors regulating KLF4 as premises to develop effective therapies for SSc-ILD. To
accomplish this, Dr. Renaud will (1) determine the involvement of HDAC(s) in the transcriptional repression of
KLF4 in pFBs, (2) build a comprehensive regulatory network based on differentially expressed (DE) genes,
microRNAs, and long non-coding RNAs (lncRNAs) to identify and validate the role of miRNAs and lncRNAs in
the regulation of KLF4 and (3) track KLF4 regulation within the different cell types and subpopulations of
fibroblasts present in lung tissues.
 Dr. Renaud is a molecular/cellular biologist in the Division of Rheumatology at the Medical University of
South Carolina (MUSC). Her long-term career goal is to become an independent translational researcher in
fibrosis with a specific interest in epigenetic factors that regulate early phases of fibrosis. To facilitate her
transition into an independent investigator, she seeks to further her training in bioinformatics and computational
tools for the analysis of single-cell RNAseq data, and in the field of network biology. Dr. Renaud’s successful
transition to an independent career will be supported by (1) her primary mentor Dr. Feghali-Bostwick an authority
in SSc research with an excellent track record of mentorship, (2) an advisory committee with the relevant
expertise, (3) institutional centers and cores, and (4) the Department of Medicine’s support and robust
mentorship program.
 By defining the epigenetic factors responsible for KLF4 downregulation in SSc-ILD, therapeutic strategies
aiming to restore antifibrotic levels of KLF4 can be developed to prevent, stop, and possibly reverse the
progression of fibrosis. The results of this proposal will provide critical preliminary data supporting extramural
applications. The proposed training will enable Dr. Renaud to achieve her long-term objective of becoming an
independent investigator.

## Key facts

- **NIH application ID:** 10885288
- **Project number:** 1K01AR083019-01A1
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Ludivine Renaud
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $119,986
- **Award type:** 1
- **Project period:** 2024-05-15 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10885288

## Citation

> US National Institutes of Health, RePORTER application 10885288, Epigenetic Regulation of KLF4 in SSc-associated lung fibrosis (1K01AR083019-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10885288. Licensed CC0.

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