Adam S. Helms

The paper maps and redesigns the MYBPC3 promoter to enhance expression and treat haploinsufficient hypertrophic cardiomyopathy.

This paper introduces a framework to model haploinsufficiency-mediated human disorders by modulating gene dosage through splicing, demonstrating its application in creating accurate animal models for cardiomyopathies.

The paper reclassifies genetic variants in HCM patients using a large registry, finding 10% of variants were reclassified, with most VUS unlikely to be causal.

This study identifies pathogenic MYBPC3 missense variants in HCM patients and shows they disrupt protein interactions and alter proximity to thin-filament proteins.

The paper investigates E-rich domain variants of RBM20, showing they reduce protein abundance and cause splicing defects, but are not rescued by RBM20 overexpression.

The paper shows that recruiting transcription factors to non-regulatory genomic sites can create enhancers or repressors, influencing gene expression at a distance with nonlinear dependence on site distance.

The paper integrates genomic and structural data to identify variant intolerance regions in cardiac sarcomere genes and links them to disease mechanisms in hypertrophic cardiomyopathy.

This study shows that FICD deficiency protects mice from heart failure by enhancing BiP-mediated UPRER and ER-phagy under stress.

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

This paper introduces a probabilistic framework to integrate TWAS and colocalization analysis, improving gene implication and pathway identification for complex traits.

This study investigates the role of ASXL3 in cardiac development using mouse and human models, finding that its loss leads to cardiac abnormalities and extracellular matrix dysfunction.

The paper uses STRUM to predict subdomain stability in MYBPC3 variants, showing that variants causing misfolding are associated with higher adverse event rates in HCM patients.