MAE Speaker Series Seminar on Mechanical control of fibrosis
Professor Guy M. Genin Co-Director, NSF Science and Technology Center for Engineering MechanoBiology Co-Director, CVISE, The Center for CardioVascular Research Innovation in Surgery and Engineering Harold and Kathleen Faught Professor of Mechanical Engineering Washington University in St. Louis This seminar will be chaired by A/P Huang Changjin. |
| Seminar 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 crosslinking 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. We have developed predictive models that capture this recursive feedback and implicate a specific aspect of matrix mechanics as a reversible lynchpin of this cycle: cross-linking of ECM by advanced glycation end products. We demonstrate that, by interrupting this crosslinking either chemically or mechanically, we can reverse fibrosis in a mouse model of established pulmonary fibrosis. |
| Speaker's Biography |
| Prof 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 Chair 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. |