Lab News

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.

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.

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.

Here, we examined how the sarcomeric myosin MYH7b is structurally, mechanically, and kinetically tuned for its unique role in specialized muscles.

Publication can be found here.

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.

The Greenberg lab welcomes Brent Scott, PhD as a new postdoc in the lab.

The Greenberg lab, together with collaborators Kory Lavine and Nate Huebsch, received a Transformational Project Award entitled “Human heart-on-a-chip to study the immune system in cardiac disease pathogenesis and repair”.

Ankit Garg presented his data at the American Heart Association BCVS meeting: P1059 / P1059 – Establishing The Mechanistic Basis Of Dilated Cardiomyopathy Associated With The Skeletal Muscle Actin Mutation R256H.

In collaboration with the Gurnett and Johnson labs, we looked at pathogenic mutations in tropomyosin that cause various forms of skeletal myopathies and birth defects.

McAdow J, Yang S, Ou T, Huang G, Dobbs MB, Gurnett CA, Greenberg MJ, Johnson AN. A pathogenic mechanism associated with myopathies and structural birth defects involves TPM2 directed myogenesis. JCI Insight. 2022 May 17:e152466. doi: 10.1172/jci.insight.152466. Epub ahead of print. PMID: 35579956.