Establishing a Spatially–Integrated Transcriptomic, Epigenomic, and Histologic Signature of Fibrosis in Systemic Sclerosis

Michael Longaker, MD
Stanford University School of Medicine
Howard Chang, MD, PHD
Stanford University School of Medicine
Howard Hughes Medical Institute

Project Overview

Drs. Longaker and Chang’s groups will use newly developed techniques to define a “spatial map” of skin and lung fibrosis and determine how it changes over time.  Cells live in and respond to their neighborhoods; in other words, their behavior is affected by neighboring cells and by the extracellular matrix surrounding them.  Drs. Longaker and Chang believe that by understanding the features of cellular neighborhoods in fibrotic tissue they will be able to identify cells and molecular pathways that can be targeted by new or existing drugs to resolve or prevent fibrosis. 

Their groups will study a mouse model of fibrosis as well as skin and lung tissue from scleroderma patients using new techniques that allow them to determine all of the gene expression activity in the tissue sample and to pinpoint cell by cell and neighborhood by neighborhood how cells are behaving.  Using a novel algorithm developed by Dr. Longaker’s group, they will be able to characterize the extracellular matrix that is associated with that gene expression activity. By integrating all of these different types of information, they will create a fine, detailed map of how cells function in fibrotic tissues. This is a new way to examine fibrotic tissues that is unprecedented in its scale and depth and will give researchers new insights into fibrosis and the potential therapies that can reduce this burden for patients.

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