Monday Muscle Seminar M&Ms: Benjamin Prosser

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Microtubules in Cardiac Mechanics and Growth

Benjamin Prosser

Assistant Professor of Physiology, Perelman School of Medicine

In heart muscle cells, the interaction of sarcomeric actin and myosin provides the force required for the heart to beat, and as such has been extensively well-studied.  Our lab, however, has focused on the much less well-studied non-sarcomeric cytoskeleton – specifically the microtubule network – as a key contributor to cardiomyocyte mechanics and mechanobiology.  In 2016, we identified novel load-bearing behavior of the microtubule network in beating cardiomyocytes, and identified post-translational microtubule detyrosination as a key regulator of the mechanical properties of heart cells (Robison et al., Science 2016).  In 2018, we found that suppressing detyrosination can lower stiffness and robustly improve contractile function in cardiomyocytes from patients with heart failure (Chen et al., Nature Medicine 2018). More recently, we have homed in on a therapeutic target and patient population, first by identifying that detyrosinated microtubules contribute to diastolic dysfunction in human heart tissue (Caporizzo et al., Circulation 2020), and second by genetically silencing the detyrosinating enzyme VASH1 to restore diastolic function in this context (Chen and Salomon, Circulation Research 2020). While we are keen to pursue these translational goals, we are also still fascinated by the fundamental mechanisms by which microtubules contribute to cardiomyocyte homeostasis and growth.  Our latest work (Scarborough and Uchida, Nature Communication 2021) identifies an essential role of microtubules in cardiac hypertrophy, as microtubules orchestrate the spatial positioning of new protein synthesis to allow heart cells to grow at the appropriate place and time.  In sum, the work has identified cardiomyocyte microtubules as key regulators of cardiac growth and mechanics, and illustrates the potential for targeting microtubules as a new therapeutic strategy for the treatment of heart failure.

More information on Benjamin Prosser lab’s webpage and on his biosketch.

Date: 19 April 2021

Time: 00:00 - 00:00

Location: Visioconference

Monday Muscle Seminar - M&M's

Benjamin Prosser