A Gene Expression Map of Scleroderma

Michael L. Whitfield, PhD

Geisel School of Medicine at Dartmouth

About Dr. Whitfield
Project Overview

The Whitfield lab’s goal is to understand the patient-to-patient variability observed in systemic sclerosis (SSc) and to identify the changes in organs at the molecular level (i.e. what genes are changing) that drive the disease. Among patients that are given the same clinical diagnosis (e.g. diffuse SSc), they have observed different groups of patients with different sets of genes turned on.

These represent molecular subsets of SSc (inflammatory, fibroproliferative, normal-like and limited), which predict response to therapy in SSc clinical trials. These subsets appear to be a common feature of all SSc tissues analyzed, particularly targeted organs (like skin and lung), and likely represent stages in disease pathogenesis.

The Whitfield lab has used genomic analyses of SSc and healthy patient biopsies, computational tools, and multiple cell culture-based and animal model systems to develop a model for how scleroderma initiates and progresses. Their data suggest that ‘immune-fibrotic’ cell-cell interactions between myeloid cells and fibroblasts drives disease.

The lab’s recent focus has been to test this model in multiple ways (computationally and experimentally), in order to better understand how disease develops, guide treatment decisions, and to aid in developing novel therapies.

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