Post-translational detyrosination of microtubules governs the mechanical performance of the heart

Friday, October 16, 2020

Dr. Mathew Caporizzo

University of Pennsylvania

Time: 4:45 PM

Location: Hand 1100


Microtubules (MTs) are stiff polymeric tubes that serve as structural components of the cytoskeleton and as highways for intracellular transport.  A diverse family of associated proteins (MAPs) bind to microtubules influencing their stability, interaction with other organelles, and transport of cargo.  MAP affinity for the microtubule is in-turn regulated by enzymatic modification of tubulin known as post-translational modification.  In the heart, there a dense network of microtubules that is dynamic and heavily post-translationally modified.  In heart disease, the balance of MT post-translational modifications becomes shifted.  Specifically, we have observed increased microtubule stability and detyrosination that correlates with increased myocyte stiffness and reduced contractile function.  Using genetic manipulation of the tyrosinating and detyrosinating enzymes, we are able to restore microtubule tyrosination and some of the mechanical performance of failing human cardiomyocytes.   The results underscore the importance of cytoskeletal post-translational modification in myocyte function and suggest an exciting new therapeutic approach for the treatment of heart failure.


Dr. Caporizzo is a research associate in the University of Pennsylvania’s department of Physiology.  He received his Ph.D. in Materials Science Engineering from the University of Pennsylvania in 2008 where he pioneered novel methods for interrogating the viscoelasticity of single cells by atomic force microscopy.  His current research program focuses on understanding the mechanical feedback driving cardiac remodeling, particularly how the non-sarcomeric cytoskeleton influences myocardial viscoelasticity and in-turn cardiac diastolic performance.  Harnessing a background in engineering, Dr. Caporizzo’s research integrates multiscale mechanical testing techniques with sub-diffraction microscopy to visualize the deformation of extracellular and cytoskeletal structures during mechanical loading.  His research aims to decipher the molecular regulators of cardiac mechanical changes in heart failure and develop novel strategies to reverse pathological remodeling.

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