Project Overview

Dr. Wernig: Scleroderma is a terrible and disfiguring disease; it mostly affects the skin and vasculature, but when it involves internal organs, the prognosis is quite poor. The disease is characterized by the onset of progressive scarring of yet unknown cause, and its underlying molecular mechanism is not well understood. There are no curative treatments other than bone marrow transplantation, which is associated with increased complications in these patients. We recently discovered that c-JUN is activated in fibroblasts in scleroderma patients and caused fibrosis reminiscent of scleroderma when induced in adult mice. This is a significant observation, because it represents a non-chemical, purely genetic, inducible model of scleroderma and highlights one critical transcription factor at the core of a general fibrotic response. In particular, two immune-regulatory proteins (checkpoint molecules) have stood out from our analyses in mice and patients. This is of particular interest because excellent reagents have already been developed by multiple pharmaceutical companies to target immune checkpoint molecules for cancer.

The main goal of our project now is to interrogate the role of immune checkpoint inhibitors in scleroderma and to determine whether they are safe and effective to use.

Role of the Scleroderma Research Foundation

The annual SRF Workshop in San Francisco is one of the best meetings in the field of fibrosis; the scientific community assembled and connected through SRF and the spectrum and quality of research impresses me each time. Investigators are extremely collaborative and focused on innovating to find cures for scleroderma, and there is always new learning. Also, I met many of my current collaborators, including some of my mentors at the annual SRF Workshop. The SRF has become “THE Platform” for scientific innovations for scleroderma and they also foster academic and industry collaborations in an unprecedented way.