01Aug 2019 by Michael Greenberg

Greenberg lab receives a grant from the Children’s Discovery Institute to study pediatric heart failure

Together with Kory Lavine and Kathleen Simpson, the Greenberg lab received a Large Scale Interdisciplinary Research Initiative Grant from the Children's Discovery Institute. The project, "Redefining Pediatric Dilated Cardiomyopathy through Precision Medicine" brings together a team of basic scientists and physician scientists to better understand pediatric heart failure and to develop novel therapeutics.
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21Feb 2019 by Michael Greenberg

New preprint from the Greenberg Lab – Disrupted mechanobiology links the molecular and cellular phenotypes in familial dilated cardiomyopathy

https://www.biorxiv.org/content/10.1101/555391v1 Sarah R Clippinger, Paige E Cloonan, Lina Greenberg, Melanie Ernst, W. Tom Stump, Michael J Greenberg Familial dilated cardiomyopathy (DCM) is a leading cause of sudden cardiac death and a major indicator for heart transplant. The disease is frequently caused by mutations of sarcomeric proteins; however, it is not well understood how these molecular mutations lead to alterations in cellular organization and contractility. To address this critical gap in our knowledge, we studied the molecular and cellular consequences of a DCM mutation in troponin-T, ΔK210. We determined the molecular mechanism of ΔK210 and used computational modeling to predict that the mutation should reduce the force per sarcomere. In mutant cardiomyocytes, we found that ΔK210 not only reduces contractility, but also causes cellular hypertrophy and impairs cardiomyocytes ability to adapt to changes in substrate stiffness (e.g., heart tissue fibrosis that occurs…
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21Feb 2019 by Michael Greenberg

New preprint from the Greenberg Lab – Computational tool to study perturbations in muscle regulation and its application to heart disease

https://www.biorxiv.org/content/10.1101/548404v3 Samantha K Barrick, Sarah R Clippinger, Lina Greenberg, Michael J Greenberg Striated muscle contraction occurs when myosin thick filaments bind to thin filaments in the sarcomere and generate pulling forces. This process is regulated by calcium, and it can be perturbed by pathological conditions (e.g., myopathies), physiological adaptations (e.g., β-adrenergic stimulation), and pharmacological interventions. Therefore, it is important to have a methodology to robustly determine the mechanism of these perturbations and statistically evaluate their effects. Here, we present an approach to measure the equilibrium constants that govern muscle activation, estimate uncertainty in these parameters, and statistically test the effects of perturbations. We provide a MATLAB-based computational tool for these analyses, along with easy-to-follow tutorials that make this approach accessible. The hypothesis testing and error estimation approaches described here are broadly applicable, and the provided tools work…
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