Funding outcome

Scleroderma is a rare but lethal autoimmune disease with no effective treatment(s). It mostly affects women and causes severe organ damage from scarring throughout various organs such as the skin and the lungs. The cells that cause this scarring (fibroblasts) behave like cancer cells. Data from our lab suggests that like cancer cells, skin cells from patients with severe scleroderma develop DNA breaks that lead to mutations. DNA mutations and breaks in cancer are thought to promote inflammation, and the mechanisms driving this may not be the same in men and women. We have identified a novel molecular mechanism in skin cells from women with scleroderma that links broken DNA with inflammation. In this proposal, I hypothesize that abundant DNA break promote this pathway and inflammation in this disease like cancer. I will better define this pathway in cells derived from women with mild or severe scleroderma and compare them with cells from healthy women. Because scleroderma (in general) is very rare in men, we will compare some of our findings in cells from a few men with severe scleroderma. Then, I will confirm my results in a novel human artificial skin model that contains skin cells from patient's scleroderma. This powerful model will allow us to also determine how this pathway affects immune cells from healthy women or women with scleroderma. Results from my research is directly translatable to patients, and may lead to new treatments in the future that target this pathway.