February 13
@
12:00 PM
–
1:00 PM
Vascular Dysfunction in Disease: Engineering Mechanobiology Holds the Solution
Shailaja Seetharaman, PhD
Postdoctoral Researcher
James Franck Institute and Department of Physics
University of Chicago
Abstract:
Abnormalities in blood vessel and blood flow properties are key drivers of severe cardiovascular and cerebrovascular pathologies. The remarkable ability of the vasculature to sense and respond to mechanical and biochemical signals across multiple scales presents both a challenge for understanding disease progression and an opportunity for therapeutic intervention. In this talk, I will first present our recent findings on uncovering novel mechano-biochemical feedback loops that drive endothelial dysfunction in atherosclerosis. I will highlight how blood flow profiles trigger transcriptional control of force-sensitive proteins, which mediate cytoskeletal crosstalk and cellular adaptation during endothelial dysfunction. Second, building on these mechanistic insights into molecular feedback and cellular structural rearrangements, I will describe our development of one of the first ‘biologically-informed’ ML models for predicting tissue-scale function in health and disease. This work opens new avenues for decoding mechano-biochemical feedback across scales in cardio- and cerebrovascular diseases. Finally, I will outline how this integrated approach enables engineering of physiological vascular tissue function and AI-mediated discovery of disease drivers, with the ultimate goal of targeting vascular functions to reverse disease progression.
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