Odell Lab

Fibrosis is an immune-mediated process that leads to abnormal collagen deposition in different organs. It contributes to almost half of all deaths as an end result of chronic inflammation in diseases such as atherosclerosis, chronic kidney disease, and inflammatory bowel disease. Scleroderma is the prototypic fibrotic disease and causes devastating fibrosis in the skin, lungs, and other organs. In the skin, it leads to debilitating contractures and in the lung, it causes progressive asphyxiation and death. Although its molecular pathogenesis is becoming clearer, there are few therapies that have a significant impact.

A fundamental question that drives our work is how immune cells interact with skin fibroblasts and keratinocytes to regulate tissue fibrosis. The disease is likely mediated by hematopoietic cells, as evidenced by the development of sclerotic graft-versus-host disease (GvHD) after stem cell transplant, which, while not the same disorder, can mimic scleroderma both clinically and histologically. Many studies have focused on how fibroblasts contribute to the excess of extracellular matrix protein in fibrotic skin, but the cellular and molecular mechanisms driving fibroblast dysregulation remain to be explored in depth. We focus on patient-based translational studies as well as basic science approaches with mouse genetics and in vitro cell cultures to understand how immune-mesenchymal interactions are important for fibrosis development and maintenance.