Lab News

New Greenberg lab publication

In collaboration with the Lin and Stitziel labs, we applied our biophysical tools to study a de novo variant found in a patient with heart failure.  We show how these tools can be used to provide insights into the potential pathogenicity of rare variants and harnessed to identify potential precision medicine therapeutics.  The paper can be found here.

New Greenberg lab publication

In collaboration with the Leinwand and Bowman labs, we show that the dynamics of myosin play a critical role in determining drug specificity.  The paper can be found here.  Congratulations to all of the authors.

New Greenberg lab preprint looking at how the cardiac myosin working stroke is modulated by the thin filament

Human heart contraction is powered by the molecular motor β-cardiac myosin, which pulls on thin filaments consisting of actin and the regulatory proteins troponin and tropomyosin. In some muscle and non-muscle systems, these regulatory proteins tune the kinetics, mechanics, and load dependence of the myosin working stroke. Despite having a central role in health and disease, it is not well understood whether the mechanics or kinetics of β-cardiac myosin are affected by regulatory proteins. We show that regulatory proteins do not affect the mechanics or load-dependent kinetics of the working stroke at physiologically relevant ATP concentrations; however, they can affect the kinetics at low ATP concentrations, suggesting a mechanism beyond simple steric blocking. This has important implications for modeling of cardiac physiology and diseases.

Paper can be found here.

New collaborative preprint between the Greenberg, Bowman, and Leinwand labs examining the how drugs target specific myosin isoforms.

Specific myosin isoforms have emerged as drug targets in diseases including heart failure, cancer, muscle diseases, and parasitic infections; however, targeting specific myosins without affecting others has been challenging since most myosins share a common structure.  Here, we show that the structural dynamics play a critical role in determining drug specificity. The understandings gleaned from this study will help with the design of new therapeutics targeting specific myosin isoforms.

To read the paper, click here.