Grant: Project Grant

The human body has conserved steps in all tissues that ensure that any damage is minimized, with structure and function of the underlying tissue preserved. Regeneration is used to describe the ideal setting where a damaged tissue is correctly reverted to the original state. In contrast, repair is reserved for when a damaged tissue is incompletely reverted to the original state and develops structural abnormalities and dysfunction. Repeated cycles of damage contribute to tissue fibrosis, a feature that accounts for 40% of all deaths from chronic diseases. Our overarching goal is to explore novel biology that regulates lung fibrosis using a 3D bioprinted, human tissue derived, on demand, model of fibrosis that incorporates the dynamic mechanical forces and biochemical cues that would be experienced in situ. Our overarching hypothesis is that the 3D microenvironment transduces mechanical and biochemical signals to cells during actuation that are important in regulating healthy and fibrotic processes. The main research objectives will focus on lung tissue and include the following: 1 - Determine the influence of mechanical and biochemical compositions in healthy and fibrotic tissue on fibroblast phenotype and function 2 - Determine the mechanisms that regulate spatial distribution of fibrotic foci in human lungs 3 - Define the molecular mechanism of how a novel transcription factor regulates fibrotic processes in human lung fibroblasts. We are uniquely positioned to deploy an innovative platform technology to study dynamic cell interactions within the lung 3D microenvironment in a spatially, mechanically, and biochemically controlled manner, which will generate basic science knowledge and technology relevant for understanding lung fibrosis.