Multi-omic Profiling of Interstitial Lung Disease in Systemic Sclerosis

Dr. Paul Wolters, MD
UC San Francisco

Gerlinde Wernig, MD
UC San Francisco

Howard Chang, MD, PhD
Stanford University
Howard Hughes Medical Institute

Project Overview

Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is one of the leading causes of scleroderma-related mortality for patients. Despite ongoing research, the molecular mechanisms that cause SSc-ILD remain poorly understood. While animal models of disease recapitulate some features of pulmonary fibrosis, their usefulness for understanding SSc-ILD is limited due to their differences from human disease. The goal of this combined USCF and Stanford collaborative effort is to generate histologic, transcriptomic, epigenomic, and proteomic data from fresh SSc-ILD lung tissues (and matched control tissues) using a multi-omics profiling approach, which will include single-cell RNA sequencing (scRNA-seq), single-cell ATAC-seq (scATAC-seq), and CYTOF. At the same time, project researchers will investigate the two subclassifications of SSc-ILD types, Usual Interstitial Pneumonia and Nonspecific Interstitial Pneumonia, using single-nuclear RNA sequencing on archived lung samples.

How this work will impact patients

This collaborative multi-institutional project will generate data that will not only enable a detailed understanding of the cellular and molecular makeup of SSc-ILD lungs, but also will enhance our understanding of the two main classifications of SSc-ILD: Usual Interstitial Pneumonia and Nonspecific Interstitial Pneumonia. This important opportunity will provide much-needed information about human SSc-ILD that is impossible to acquire by other methods and cannot be obtained from animal models. In addition, direct comparison of the SSc-ILD data to similar data obtained from Idiopathic Pulmonary Fibrosis (IPF) patients, which members of this team have previously generated, will enable a detailed dissection of the similarities and differences between the two fibrotic lung diseases. This project- the first of its kind in SSc- will substantially advance our understanding of SSc-ILD and help to inform the development of new therapies.

Role of the Scleroderma Research Foundation

Members of this team have long-standing research relationships with the Scleroderma Research Foundation which has been a critical partner involved in all phases of planning and developing this important opportunity. The SRF is also the sole funder of this work.

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