Stuart A. Cook

This study evaluates polygenic scores for hypertrophic cardiomyopathy (HCM) in the general population and clinical settings, showing increased risk with higher scores and potential for clinical application.

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.

This study identifies ST2-expressing fibroblasts as drivers of Peutz-Jeghers syndrome polyposis and shows IL-11 as a therapeutic target.

This paper identifies direct cardiomyocyte toxicities of IL11 therapy, showing it causes acute heart failure by activating JAK/STAT3, which questions its continued use in patients.

This paper estimates the penetrance of rare variants in cardiomyopathy genes using cross-sectional data from genetic testing, finding substantial penetrance for dominant cardiomyopathies and variant-specific differences.

This study shows that IL11 expression in cardiomyocytes causes cardiac fibrosis, inflammation, and dysfunction, contradicting previous reports of its anti-fibrotic effects.

This study shows that inhibiting IL11 improves healthspan in aged mice by reversing metabolic dysfunction, sarcopenia, and frailty.

This study shows IL11 promotes inflammation in fibroblasts by upregulating IL33 and other proinflammatory genes, with STAT3 signaling being critical for this effect.

This study identifies IL11's role in inhibiting LKB1/AMPK and activating mTOR through ERK/P90RSK, leading to metabolic dysfunction and fibrosis in multiple cell types and NASH in mice.

This study examines the clinical impact of rare variants in HCM-associated genes in the UK Biobank, finding that pathogenic variants are linked to increased cardiovascular risk and subclinical phenotypes, while non-pathogenic variants show minimal effect.

The paper identifies a frameshift variant in MYH7 associated with HCM in an Egyptian cohort, revealing a new pathogenic mechanism involving distal PTC escape from NMD.

This study compares IL11 and IL11RA1 knockout mice, finding IL11 deficiency protects against lung fibro-inflammation but causes infertility, while IL11RA1 deficiency leads to craniosynostosis.

The paper investigates IL11-driven fibrosis mechanisms, showing ERK, not STAT3, drives fibrogenesis and identifies a novel role for nintedanib in inhibiting pro-fibrotic translation.

The paper identifies non-coding variants upstream of MEF2C causing severe developmental disorder through three distinct loss-of-function mechanisms, showing their diagnostic importance in existing exome datasets.

This study identifies genetic overlaps and distinct variant classes in LVNC compared to DCM and HCM, revealing both shared and unique genetic mechanisms.

This study performs a large GWAS on dilated cardiomyopathy, identifying two new loci and confirming two existing ones, with potential therapeutic implications.

This study shows that family history collection improves the detection of pathogenic variants in genomic data, enhancing precision medicine by identifying high-risk individuals.

The paper shows that autocrine IL11 signaling in hepatocytes drives lipotoxicity and NASH by causing lipoapoptosis and reactive oxygen species, with protection seen in Il11ra1-deleted mice.

The paper describes the EHVol study, a genomic database of 391 Egyptian healthy volunteers to improve representation in global genomic databases and aid in variant interpretation for North African populations.

This paper introduces CardioBoost, a disease-specific variant classifier for inherited cardiac conditions, showing improved accuracy in predicting pathogenicity compared to genome-wide tools.

The paper identifies genetic associations with myocardial trabecular complexity using UK Biobank data and shows a causal link to ventricular function and electrical activity.

The paper introduces Xtail, a method to identify differentially translated genes by analyzing Ribo-seq data while accounting for mRNA abundance variations.

This study presents whole-genome sequencing data from 4,810 Singaporeans across three ethnic groups, revealing genetic structure, admixture, and improved imputation for Asian and Oceanian populations.

The paper identifies IL-11 as a therapeutic target in idiopathic pulmonary fibrosis by showing its role in fibroblast activation and fibrosis progression across species.

The paper identifies translational regulators of fibrogenic genes in human cardiac fibroblasts and shows their role in cardiac fibrosis through ribosome profiling and RNA-binding protein analysis.

This study identifies IL-11 as a key driver of HSC-to-myofibroblast transformation in NASH, showing that targeting IL-11 reduces fibrosis and inflammation in preclinical models.

The paper quantifies variant pathogenicity in hypertrophic cardiomyopathy using etiological fraction, increasing actionable variant detection by 14-20%.

The paper responds to a critique of their variant filtering method, demonstrating its robustness and highlighting the benefits of using high-resolution variant frequencies for clinical genome interpretation.

CardioClassifier is a decision-support tool for inherited cardiac conditions that improves variant interpretation by integrating disease-specific annotations and case data.

The paper presents a statistical framework to filter candidate disease-causing variants using high-resolution variant frequencies, reducing the number of variants under consideration and reclassifying some as pathogenic.