Kenneth B. Margulies

ROR2 drives right ventricular heart failure via disruption of proteostasis

This study identifies ROR2 as a driver of right ventricular failure by disrupting proteostasis, showing that modulating ROR2 can rescue structural and functional deficits in cardiomyocytes.

Impaired proteostasis is an early feature of the diabetic heart in humans and mice

This study shows that impaired proteostasis is an early feature of diabetic cardiomyopathy in humans and mice, with intermittent fasting offering protective effects.

SGLT2 inhibitors activate pantothenate kinase in the human heart

This study identifies that SGLT2 inhibitors activate pantothenate kinase 1 (PANK1) in the human heart, enhancing coenzyme-A synthesis and fuel use, which may explain their clinical benefits in heart failure.

Label free multimodal optical imaging of metabolic heterogeneity and correlation in aging by integrating SRS, MPF, FLIM, and SHG

The paper introduces MANIFEST, a label-free imaging platform that integrates multiple optical modalities to analyze metabolic heterogeneity and spatial correlations in aging and disease models.

SureQuant IS-PRM Enables Cross-Species Targeted Quantification of Retinoid Metabolism and Signaling Proteins in the Heart

The paper develops a targeted proteomics method to quantify retinoid metabolism and signaling proteins across species and tissues, revealing tissue-specific networks and developmental changes in the heart.

Load-Dependent Effects of Sodium Glucose Co-Transporter Inhibitors on Work in Human Hypertrophic Cardiomyopathy Living Myocardial Slices.

This study uses human living myocardial slices to examine how sodium glucose co-transporter inhibitors affect myocardial work in hypertrophic cardiomyopathy under varying loading conditions.

Integrated single-cell and spatial multiomic analysis reveals widespread reactivation of developmental programs in diseased human hearts

The paper integrates single-cell and spatial multiomic data to show widespread reactivation of developmental programs in diseased human hearts, with insights into transcriptional factors and localized fetal reactivation.

Microtubule detyrosination alters nuclear mechanotransduction and leads to pro-hypertrophic signaling in hypertrophic cardiomyopathy

This study shows that microtubule detyrosination in HCM causes nuclear shape changes and YAP1 signaling, which can be reversed by inhibiting detyrosination.

Increased CPT1a expression is a critical cardioprotective response to pathological stress that suppresses gene programs for remodeling and enables rescue by gene transfer

This study shows that increased CPT1a expression protects the heart from pathological stress by suppressing harmful gene programs, and gene transfer can rescue cardiac function in disease models.

Telomere 3'-overhang attrition and persistent telomeric DNA damage response in failing human hearts

The paper investigates telomere dysfunction in failing human hearts, finding 3'-overhang attrition and DNA damage responses in cardiomyocytes from idiopathic dilated cardiomyopathy and ischemic heart disease.

Matrix Stiffening Induces Mechanical Memory and Nuclear Fragility in Cardiomyocytes via Microtubule-Lamin Coupling

This study shows that short-term mechanical stress in cardiomyocytes leads to persistent nuclear changes and DNA damage, which can be prevented by disrupting microtubule detyrosination or the LINC complex.

Ultrastructure analysis of mitochondria, lipid droplet and sarcoplasmic reticulum apposition in human heart failure

This study examines changes in organelle apposition in human heart failure cardiomyocytes, finding increased distances between mitochondria and sarcoplasmic reticulum/lipid droplets, along with altered molecular tethers.

Cardiac fibroblasts counterbalance cardiomyocytes in LMNA cardiomyopathy pathogenesis

The paper investigates the role of lamin A/C in cardiac fibroblasts and shows that mutations affect fibroblast function, influencing disease progression in LMNA cardiomyopathy.

Desmoplakin Haploinsufficiency Underlies Cell-Cell Adhesion Failure in DSP Cardiomyopathy and is Rescued by Transcriptional Activation

This study shows that DSP haploinsufficiency causes cell-cell adhesion failure in cardiomyopathy and that increasing DSP expression rescues this defect.

Single cell transcriptomic analyses of human heart failure with preserved ejection fraction

This paper uses snRNA-seq to analyze human HFpEF myocardium, identifying differential gene expression and pathway enrichment in cardiomyocytes and fibroblasts compared to controls and DCM.

Phosphorylation of CRYAB Induces a Condensatopathy to Worsen Post-Myocardial Infarction Left Ventricular Remodeling.

This study shows that phosphorylation of CRYAB leads to condensate formation and worsens heart failure after myocardial infarction.

Genome-wide association analysis reveals insights into the molecular aetiology underlying dilated cardiomyopathy

This study identifies 80 genetic loci and 61 effector genes associated with dilated cardiomyopathy through GWAS and integrates transcriptomic data to uncover biological pathways and cellular states involved in the disease.

Epigenome-wide association study for dilated cardiomyopathy in left ventricular heart tissue identifies putative gene sets associated with cardiac development and early indicators of cardiac risk

This study identifies 194 epigenome-wide significant CpGs associated with dilated cardiomyopathy (DCM) and links them to cardiac gene expression and cardiovascular risk factors.

Genome-Wide Fetalization of Enhancer Architecture in Heart Disease

The paper identifies widespread epigenomic changes in idiopathic dilated cardiomyopathy, showing a shift toward fetal-like enhancer states and providing a data resource for further study.

Transcriptional, post-transcriptional, and post-translational mechanisms rewrite the tubulin code during cardiac hypertrophy and failure

The paper investigates how the tubulin code is rewritten during cardiac hypertrophy and failure through transcriptional, autoregulatory, and post-translational mechanisms.

Transcriptional and Cellular Diversity of the Human Heart

The paper uses single-nucleus RNA sequencing to define the transcriptional and cellular diversity of the non-failing human heart, identifying 9 major cell types and 20 subclusters.

Detailed Regulatory Interaction Map of the Human Heart Facilitates Gene Discovery for Cardiovascular Disease

The paper generates Hi-C data from human cardiac tissue and develops a method to identify regulatory interactions, showing how disease variants intersect with these interactions to prioritize causative genes.

Genome-wide association study provides new insights into the genetic architecture and pathogenesis of heart failure

This study conducts a large GWAS on heart failure, identifying 12 genetic loci with associations to CAD, atrial fibrillation, and reduced left ventricular function, and provides causal evidence for several risk factors.

Disease and phenotype relevant genetic variants identified from histone acetylomes in human hearts

The paper identifies genetic variants associated with heart failure by analyzing histone acetylation QTLs in human heart tissue.

Pathologic gene network rewiring implicates PPP1R3A as a central cardioprotective factor in pressure overload heart failure

The paper identifies PPP1R3A as a central cardioprotective factor in pressure overload heart failure by analyzing gene network rewiring in human hearts.