# Regulatory roles of peptidylarginine deimination in elastogenisis

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $525,171

## Abstract

Project Summary
Elastic fibers provide the elasticity that is essential for the function of many organs/tissues, such as lung, large
arteries, and skin. Congenital deficiency or destruction/degradation of elastic fibers can lead to emphysema,
arterial aneurysm, and laxity of tissues. Reversely, excessive formation of elastic fibers is a feature of
pleuroparenchymal fibroelastosis, which is currently without any effective treatment. Many proteins are
modified after they are produced in cells. Such modification can critically influence the function of proteins. One
such modification is citrullination, which has been shown to regulate the function of various types of cells.
Aberrant citrullination has been observed in many human diseases, such as chronic obstructive lung disease,
idiopathic pulmonary fibrosis, and rheumatoid arthritis. Thus, manipulating protein citrullination can be
beneficial in many clinical settings. This project is based on a novel observation that citrullination critically
regulates the formation of elastic fibers. Its goal is to investigate the role and mechanism of action of
citrullination in regulating the formation of elastic fibers and lung function. Molecular, cellular, and biophysical
approaches will be deployed to elucidate how citrullination regulates the elastogenesis of fibroblasts (Aim 1)
and how citrullination of critical elastogenic proteins is regulated (Aim 2). Reagents detecting the citrullination
of the critical elastogenic proteins will be developed to facilitate this endeavor. Finally, genetically engineered
mice will be generated to examine cell type-specific and temporal roles of citrullination in modulating the
function of lungs and the development of emphysema induced by cigarette smoking (Aim 3). Knowledge
gained from this project very likely will uncover novel therapeutic approaches toward many human diseases,
such as emphysema and arterial aneurysm.

## Key facts

- **NIH application ID:** 10799711
- **Project number:** 5R01HL158601-03
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** I-CHENG HO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $525,171
- **Award type:** 5
- **Project period:** 2022-04-15 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10799711

## Citation

> US National Institutes of Health, RePORTER application 10799711, Regulatory roles of peptidylarginine deimination in elastogenisis (5R01HL158601-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10799711. Licensed CC0.

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