Abstract
Fibrosis, a progressive scarring of tissues affecting nearly every organ, exemplifies a class of incurable "diseases of solid mechanics" that have long resisted traditional biochemical treatment. Fibrosis can arise when cells and their extracellular matrix respond aberrantly to mechanical forces. This talk will describe how stress fields and extracellular matrix cross linking can control the degree to which cells move down a phenotypic pathway associated with disease. We have uncovered a critical mechanism: anisotropy of the stress field governs a recursive interplay between cell structure, extracellular matrix alignment, and gene expression that drives the transition of quiescent fibroblasts into disease-causing myofibroblasts. By applying integrated solid mechanics theory and experiment to biological systems, we have developed predictive models that capture this recursive feedback. These models explain why cells can turn pathological if spaced within a radius reported by Taher’s group, and enable us to propose strategies to disrupt the associated pathological mechanical feedback loops.
About the Speaker
Guy M. Genin applies solid mechanics principles to understand living systems and treat disease. He is the Harold and Kathleen Faught Professor of Mechanical Engineering at Washington University in St. Louis, and co-directs both the NSF Science and Technology Center for Engineering Mechanobiology, and the NIH-funded Center for CardioVascular Research Innovation in Surgery and Engineering. Genin serves on the U.S. Interagency Modeling and Analysis Group's steering committee and the SES Board of Directors, and is Secretary of the ASME Bioengineering Division. A fellow of ASME, AIMBE, IAMBE, and the U.S. National Academy of Inventors, Genin is also chief engineer of Caeli Vascular, Inc. and CTO of Vascora, LLC. His awards include an NIH Research Career Award for his work on the mechanics of fibrosis; the ASME Skalak award for the best ASME JBME paper; and the ASME Savio L.-Y. Woo Medal for his translational impact in mechanobiology. Genin earned a Ph.D. from Harvard and completed postdoctoral training at Cambridge and Brown.
Host: Professor Taher Saif