Next Generation Proteomics to Identify Novel Immune Targets for Scleroderma

Gerlinde Wernig, MD

Stanford University School of Medicine

About Dr. Wernig

Project Overview

The Wernig lab is working to identify fundamental differences between diseased cells in patients with scleroderma-associated interstitial lung disease (SSc-ILD) and healthy lung cells, with a focus on the role the immune system plays in these changes. Their previous studies shed light on how particular immune cells affect scleroderma progression (Wernig PNAS2017, NatureComm.2020, JCI2020), leading to the hypothesis that immunotherapy drugs may be effective treatments for scleroderma. They aim to identify proteins that are predictors of disease progression into SSc-ILD and also proteins that indicate whether a patient will respond or is responding to treatment.

The Wernig Lab’s search for cellular markers of scleroderma-associated interstitial lung disease (SSc-ILD) is being done in conjunction with their work on the Scleroderma Research Foundation-funded project titled Multi-omic Profiling of Interstitial Lung Disease in Systemic Sclerosis.  The group is using a highly innovative and transformative technology, low-input mass spectrometry, to detect low abundance proteins in SSc-ILD with the goal of identifying new cellular markers of disease and proteins that can be targeted by drugs.

Until recently, these low abundance proteins were undetectable because of the low sensitivity of conventional mass spectrometry. With this data, they will build and analyze the first database of proteins detected in each cell type of interest in human healthy vs. SSc-ILD lungs. They will also compare the healthy and scleroderma lung data to our dataset from idiopathic pulmonary fibrosis lungs.

Ultimately, it is hoped that this work will improve risk assessment and evaluation of treatment effectiveness for SSc-ILD, and that it will provide insights into attractive drug targets.

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