Tissue fibrosis affects virtually every organ system and contributes to approximately 40% of all causes of death. Collagen, the main component of fibrotic tissue, is continuously produced and degraded with a precise balance between these processes maintaining normal tissue architecture. In fibrotic disease states there is an imbalance such that collagen production outstrips collagen degradation. Seen from this perspective, fibrosis can be viewed as a disease of impaired matrix degradation as much as a disease of excess matrix production. Collagen degradation occurs by an extracellular proteolytic pathway and an intracellular pathway of cell-mediated uptake followed by lysosomal degradation.  While the extracellular-proteolytic pathway has been extensively studied, there is a relative paucity of knowledge regarding the endogenous pathways that mediate intracellular collagen degradation. Recent evidence suggests that in murine models, impaired cell-mediated collagen uptake increases the severity of experimental tissue fibrosis. Whether therapies that augment cell-mediate collagen uptake will reduce the severity of fibrosis is unknown. The overall goal of my lab is to understand the basic biological mechanisms that regulate cell-mediated collagen turnover and the implications of this process in regulating the severity of tissue fibrosis. We are specifically focused on understanding what molecular pathways cells use to remodel fibrotic tissue, whether these pathways malfunction in progressive fibrotic disease, and how these pathways can be targeted for therapies that reverse established fibrosis by augmenting cell-mediated collagen degradation.