Abstract:

Tissue mechanics drives influence cell behavior, and cell behavior drives tissue mechanics. The cellular pathways for this recursive feedback are so redundant that pharmaceutical treatment for pathologies of such feedback have limited efficacy. A key example of this is pulmonary fibrosis. This talk will present our integrated experimental and computational work demonstrating that ECM mechanics can serve as a therapeutic target. We show that stress anisotropy drives the fibroblast-to-myofibroblast underlying fibrosis, a transition accelerated  through a self-reinforcing feedback loop and long-range mechanical communication through the ECM. This communication is governed by ECM crosslinking. Findings revealed architecture-dependent mechanical responses: physiological dynamic stretching disrupts advanced glycation end-product crosslinks in porous lung-like scaffolds but not in fibrous liver-like matrices. This structure-property relationship directly modulates the nonlinearity of networked solids by controlling mechanical crosslinking. Leveraging these insights, we developed a non-invasive ventilation protocol that reverses pulmonary fibrosis in mice by physically disrupting pathological ECM crosslinks, a mechanotherapeutic approach with enhanced efficacy when combined with pharmacological AGE inhibition.

Biography:

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 served on the SES Board of Directors, and is Chair of the ASME Bioengineering Division, reporting directly to ASME BED Secretary, the legendary Craig Goergen himself. 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.

Students registered for the seminar are expected to attend in person. 

Teams ID and Passcode:

Meeting ID: 211 123 896 292 8

Passcode: Uh9qs2pf

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