Joseph C. Wu

Clinical trials in a dish: cardiometabolic drug development with biological and digital twins

Preclinical drug development has long relied on animal models to predict safety and efficacy before agents enter human trials, despite critical differences between human and animal model physiology. The withdrawal of rosiglitazone, rofecoxib, and terfenadine due to cardiovascular toxicity exemplifies the translational...

RUNX1-driven endothelial-to-mesenchymal transition contributes to remodelling in LMNA cardiomyopathy.

Myeloid cell replacement induces intercellular mitochondrial transfer and restores metabolism in a mouse model of mitochondrial disease

Friedreich’s ataxia (FA) is a mitochondrial disease caused by frataxin deficiency that leads to progressive neurodegeneration and cardiomyopathy. Effective disease-modifying therapies remain limited. Here we show that myeloid cell replacement promotes neurological and cardiac recovery in FA mice through intercellular m...

Cross-cohort analysis of expression and splicing quantitative trait loci in TOPMed.

This work fine-mapped UK Biobank-derived genome-wide association study (GWAS) signals from 164 traits and identified e/sQTL colocalizations for 10,611 GWAS signals, including 7096 that colocalize with secondary e/sQTLs.

Damaging RBM20 E-rich domain variants are not rescued by gene replacement

The data indicate that pathogenic E-rich domain variants reduce RBM20 protein abundance, but that their mechanism is unlikely to be explained by haploinsufficiency alone.