# Molecular Basis for Altered Natural Killer Cells in Systemic Sclerosis associated-Interstitial Lung Disease

> **NIH NIH P50** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $147,840

## Abstract

Cristina Padilla, MD
NIAMS Diversity Supplement
2024-2026
The Molecular Basis of Altered Natural Kill Cells in Systemic Sclerosis-associated Interstitial
Lung Disease
Project Summary
An activated, cytotoxic natural killer (NK) cell population was identified in scleroderma-associated
interstitial lung disease (SSc-ILD) that showed upregulation in several genes, including Granzyme
B, Amphiregulin, and Interferon-gamma. Because the genes are suspected to play a critical role in
the pathogenic effects in the lungs, this project will use single cell technologies, including single
cell ATAC sequencing (scATAC-seq) and Multiome-seq (combined single nuclear RNA-seq and
snATAC-seq), to understand how these genes are regulated. By assessing the state of open
chromatin across the genome using computational analysis, transcription factors (TF) can be
predicted that are regulating this process. Experiments will be utilized to better understand the
pathways that cause NK cell activation in SSc-ILD by comparing TF regulating SSc-ILD NK cells
from lung with TF activated by cytokine simulation in vitro of NK cells purified from blood and
healthy lungs. We hypothesize that open chromatin in NK cells will implicate key transcription
factors (TFs) that regulate NK cell activation in SSc-ILD lungs, and that alteration of these TFs drive
expression of AREG, IFNG and GZMB, as well as other key genes in their aberrant pathway of
differentiation.

## Key facts

- **NIH application ID:** 11087300
- **Project number:** 3P50AR080612-03S1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** ROBERT A. LAFYATIS
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $147,840
- **Award type:** 3
- **Project period:** 2024-09-20 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11087300

## Citation

> US National Institutes of Health, RePORTER application 11087300, Molecular Basis for Altered Natural Killer Cells in Systemic Sclerosis associated-Interstitial Lung Disease (3P50AR080612-03S1). Retrieved via AI Analytics 2026-06-23 from https://api.ai-analytics.org/grant/nih/11087300. Licensed CC0.

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