The Whitfield Lab is currently working on several projects that are unified by genome-wide, systems biology approaches. The lab uses genomic tools and tissue culture models to study the systemic autoimmune disease scleroderma (SSc). SSc is a rare autoimmune disease with heterogeneous clinical presentation. Despite modest advances in disease management, overall prognosis for SSc is worse than for other rheumatic diseases, and it continues to exhibit high mortality rates. Patients are classified clinically into two subgroups, limited (lcSSc) and diffuse cutaneous SSc (dcSSc), based on the extent of skin involvement. The goal of this project is to identify gene expression biomarkers that subset patients, predict clinical endpoints, and assess response to therapy.

Gene expression subsets in scleroderma. We have used genome-wide analysis of gene expression in skin to identify novel subsets of scleroderma. Genome-wide analysis has identified gene expression groups within current clinical classifications of the disease that can be mapped to distinct clinical covariates. Each group has differentially regulated pathways that could be targeted therapeutically and each is being mapped to specific mouse models that recapitulate disease phenotypes for further genetic studies. The lab is currently examining scleroderma patients for gene expression responses to therapy in order to identify biomarkers that could impact clinical decision-making. An ongoing area of investigation is to identify subsets and biomarkers in scleroderma using peripheral blood samples rather than skin samples. This would provide biomarkers in a tissue more easily accessible than skin.

Three-dimensional (3D) tissue culture models. We have developed 3D skin-like culture model system of SSc, termed self-assembled Skin Equivalents (saSE), in which we investigate SSc fibroblast activation in a 3D microenvironment.