M. J. Greenberg

Harnessing molecular mechanism for precision medicine in dilated cardiomyopathy caused by a mutation in troponin T

This study connects genotype, phenotype, and drug response in dilated cardiomyopathy using molecular mechanism-based computational and experimental approaches for a troponin T mutation.

Dilated cardiomyopathy-associated skeletal muscle actin (ACTA1) mutation R256H disrupts actin structure and function and causes cardiomyocyte hypocontractility

This study shows that the ACTA1 R256H mutation disrupts actin structure and function in cardiomyocytes, leading to reduced contractility and a likely causative role in dilated cardiomyopathy.

Insights into post-translational regulation of skeletal muscle contractile function by the acetyltransferases, p300 and CBP

This study shows that loss of p300 and CBP in skeletal muscle causes severe contractile dysfunction, but mitochondrial function and cross-bridge cycling are not the primary causes.

Divergent Molecular Phenotypes in Point Mutations at the Same Residue in Beta-Myosin Heavy Chain Lead to Distinct Cardiomyopathies

This study shows that two point mutations at the same residue in beta-myosin heavy chain cause distinct cardiomyopathies through different molecular mechanisms.

Single Molecule Mechanics and Kinetics of Cardiac Myosin Interacting with Regulated Thin Filaments

This study investigates how thin filament regulatory proteins affect the mechanics and kinetics of cardiac myosin using single-molecule techniques, finding no significant impact at physiological ATP concentrations but some effects at low ATP.

Drug specificity and affinity are encoded in the probability of cryptic pocket opening in myosin motor domains

This paper shows that the probability of cryptic pocket opening in myosin motor domains predicts drug specificity and affinity, using molecular dynamics simulations and Markov state models.

Myofilament Glycation in Diabetes Reduces Contractility by Inhibiting Tropomyosin Movement, is Rescued by cMyBPC Domains

This study identifies myofilament glycation in diabetes as a cause of reduced cardiac contractility, showing that cMyBPC domains can rescue this dysfunction.

SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis

This study shows SARS-CoV-2 infects human engineered heart tissues, causing myocarditis-like features, and identifies ACE2 and proteases as entry factors.

Computational Tool for Ensemble Averaging of Single-Molecule Data

The paper introduces a computational tool, SPASM, for ensemble averaging of single-molecule data to improve the accuracy of measuring mechanochemical coupling in molecular motors.

Mechanical dysfunction induced by a hypertrophic cardiomyopathy mutation is the primary driver of cellular adaptation

This study shows that a HCM mutation causes mechanical dysfunction, which drives cellular adaptation through altered force generation and signaling pathways.

Conformational distributions of isolated myosin motor domains encode their mechanochemical properties

The paper models conformational distributions of myosin motor domains using molecular dynamics simulations to predict mechanochemical properties better than sequence or structure alone.

Disrupted mechanobiology links the molecular and cellular phenotypes in familial dilated cardiomyopathy

This study investigates how a mutation in troponin-T affects cellular contractility and mechanosensing in familial dilated cardiomyopathy.

Computational tool to study perturbations in muscle regulation and its application to heart disease

The paper introduces a computational tool to measure muscle activation equilibrium constants and analyze perturbations, applying it to study a mutation causing hypertrophic cardiomyopathy.

Positive Cardiac Inotrope, Omecamtiv Mecarbil, Activates Muscle Despite Suppressing the Myosin Working Stroke

This study shows that omecamtiv mecarbil increases cardiac output by inhibiting myosin working stroke and enhancing thin filament activation through cooperative mechanisms.

Cooperative changes in solvent exposure identify cryptic pockets, conformational switches, and allosteric coupling

The paper introduces a method to identify functionally-relevant conformational changes in proteins by analyzing cooperative solvent exposure changes, demonstrating its utility in discovering cryptic allosteric sites.