Jonathan G. Seidman

Thick filament molecular interfaces play a critical role in pathogenesis of hypertrophic and dilated cardiomyopathy

The paper maps missense variants in cardiomyopathy genes to a cryo-EM model of the cardiac thick filament, identifying molecular interfaces critical for disease pathogenesis.

Engineered human iPS cell models reveal altered podocytogenesis and glomerular capillary wall in CHD-associated SMAD2 mutations

This study uses engineered human iPSCs to show that SMAD2 mutations linked to CHD disrupt kidney podocytogenesis and glomerular structure, leading to proteinuria.

Genome Sequencing is Critical for Forecasting Outcomes Following Congenital Cardiac Surgery

This study uses AI to show that genome sequencing can predict adverse outcomes after congenital heart defect surgery by identifying damaging genotypes in specific genes.

Genes of the fatty acid oxidation pathway are upregulated in female as compared to male cardiomyocytes

The paper identifies sex differences in cardiac metabolism, showing female hearts have higher fatty acid oxidation gene expression and energy utilization compared to male hearts.

Endocardial primary cilia and blood flow are required for regulation of EndoMT during endocardial cushion development

The paper shows that endocardial primary cilia and blood flow regulate EndoMT during cushion development by modulating KLF4 expression.

Direct Reprogramming of Non-limb Fibroblasts toCells with Properties of Limb Progenitors

This study reprograms non-limb fibroblasts into cells with limb progenitor properties using Prdm16, Zbtb16, Lin28, and Lin41.

Genetic Diagnosis of Facioscapulohumeral Muscular Dystrophy Type 1 Using Rare Variant Linkage Analysis and Long Read Genome Sequencing

This study uses rare variant linkage analysis and long-read sequencing to identify a pathogenic FSHD1 allele in a family, mapping the disease locus to chromosome 4q35.2.

Short-term Pre-operative Methionine Restriction Induces Browning of Perivascular Adipose Tissue and Improves Vein Graft Remodeling in Mice

Structural variation across 138,134 samples in the TOPMed consortium

The paper presents a comprehensive catalog of structural variants across 138,134 individuals, identifying novel variants and their associations with cardio-metabolic and hematologic traits.

A Missense Mutation in Human CHD4 Causes Ventricular Noncompaction by Repressing ADAMTS1-mediated Trabeculation Cessation

This study identifies a CHD4 missense mutation causing ventricular noncompaction by repressing ADAMTS1-mediated trabeculation cessation in mice and humans.

Modeling human TBX5 haploinsufficiency predicts regulatory networks for congenital heart disease

The paper models TBX5 haploinsufficiency in iPSC-derived cardiomyocytes to identify gene regulatory network imbalances linked to congenital heart disease.

poly(UG)-tailed RNAs in Genome Protection and Epigenetic Inheritance

The paper shows that pUG tails on RNAs enable transgenerational epigenetic inheritance by promoting gene silencing through siRNA synthesis in C. elegans.

Cells and gene expression programs in the adult human heart

The paper characterizes the cellular composition and gene expression of the adult human heart using single-cell transcriptomics, identifying distinct cell types and their functional roles.

Whole Genome De Novo Variant Identification with FreeBayes and Neural Network Approaches

The paper develops a framework for de novo variant identification using FreeBayes and a neural network, achieving high accuracy in SNVs and indels through validation with Sanger sequencing.

DNA Break-Induced Epigenetic Drift as a Cause of Mammalian Aging

The paper shows that DNA double-strand breaks induce epigenomic changes that accelerate the aging clock in mammals.

Early post-zygotic mutations contribute to congenital heart disease

The paper identifies mosaic mutations in blood and cardiac tissue from CHD patients, finding 1% of cases have detectable mosaic variants that may contribute to congenital heart disease.

Paternal-age-related de novo mutations and risk for five disorders

The paper estimates the risk of five disorders from paternal-age-related de novo mutations using whole-exome-sequencing data and Danish registry data.

Sex differences in gene expression in response to ischemia in the human myocardium

The paper identifies sex-specific gene expression changes in human myocardial tissue after ischemia, highlighting differences in pathways and cell-type proportions between males and females.

MYBPC3 Mutations cause Hypertrophic Cardiomyopathy by Dysregulating Myosin: Implications for Therapy

The paper shows that MYBPC3 mutations disrupt myosin relaxation states, leading to hyper-contractility in HCM, and that targeting myosin can alleviate these effects.

Robust identification of deletions in exome and genome sequence data based on clustering of Mendelian errors

The paper introduces MEM, a method to identify deletion CNVs in WES and WGS trio data by clustering Mendelian errors, achieving high validation rates and detecting additional de novo deletions and contamination.

Cardiac enriched BAF chromatin remodeling complex subunit Baf60c regulates gene expression programs essential for heart development and function

This study shows that Baf60c regulates gene expression programs critical for heart development and function by interacting with Myocardin and controlling contractile proteins and metabolic genes.